BTK (Bruton tyrosine kinase)

Gene

• Entrez ID: 695
• Gene name: Bruton tyrosine kinase
• Gene symbol: BTK
• Synonyms (NCBI Gene): AGMX1, AT, ATK, BPK, IGHD3, IMD1, PSCTK1, XLA
• Disease Acronyms (UniProt): AT, IGHD3, XLA
• Chromosome: X
• Chromosome location: Xq22.1
• Summary: The protein encoded by this gene plays a crucial role in B-cell development. Mutations in this gene cause X-linked agammaglobulinemia type 1, which is an immunodeficiency characterized by the failure to produce mature B lymphocytes, and associated with a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs7474275	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs28935478	T>C	Pathogenic	Coding sequence variant, intron variant, missense variant
rs41310709	G>A,T	Pathogenic	Coding sequence variant, synonymous variant, intron variant, stop gained
rs104894770	C>G	Pathogenic	Coding sequence variant, missense variant
rs128620183	C>T	Pathogenic	Coding sequence variant, missense variant
rs128620184	T>C	Pathogenic	Coding sequence variant, intron variant, missense variant
rs128620185	C>T	Pathogenic	Coding sequence variant, missense variant
rs128620186	A>G	Pathogenic	Coding sequence variant, initiator codon variant, missense variant
rs128620187	G>A,T	Pathogenic	Coding sequence variant, synonymous variant, stop gained
rs128620188	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained
rs128620189	T>G	Pathogenic	Coding sequence variant, missense variant
rs128621190	A>T	Pathogenic	Coding sequence variant, missense variant
rs128621191	C>A	Pathogenic	Coding sequence variant, stop gained
rs128621192	C>T	Pathogenic	Coding sequence variant, stop gained
rs128621193	G>A	Pathogenic	Coding sequence variant, stop gained
rs128621194	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs128621195	T>C	Pathogenic	Coding sequence variant, missense variant
rs128621196	T>G	Pathogenic	Coding sequence variant, missense variant
rs128621197	A>C	Pathogenic	Coding sequence variant, stop gained, intron variant
rs128621198	A>G	Pathogenic	Coding sequence variant, intron variant, missense variant
rs128621199	G>A,T	Pathogenic	Coding sequence variant, synonymous variant, intron variant, stop gained
rs128621200	A>G	Pathogenic	Coding sequence variant, intron variant, missense variant
rs128621201	G>A,C	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained, intron variant, missense variant
rs128621202	C>T	Pathogenic	Coding sequence variant, intron variant, missense variant
rs128621203	A>G	Pathogenic	Coding sequence variant, missense variant
rs128621204	G>A	Pathogenic	Coding sequence variant, missense variant
rs128621205	A>G	Pathogenic	Coding sequence variant, missense variant
rs128621206	T>C	Pathogenic	Coding sequence variant, missense variant
rs128621207	G>T	Likely-pathogenic	Coding sequence variant, stop gained
rs128621208	G>T	Pathogenic	Coding sequence variant, missense variant
rs128621209	C>T	Pathogenic	Coding sequence variant, missense variant
rs128621210	A>T	Pathogenic	Coding sequence variant, missense variant
rs128622211	C>A	Pathogenic	Coding sequence variant, stop gained
rs146681416	T>C,G	Likely-pathogenic, benign	Synonymous variant, missense variant, coding sequence variant
rs193922124	G>A,T	Pathogenic	Synonymous variant, coding sequence variant, intron variant, stop gained
rs193922125	T>A	Likely-pathogenic	Missense variant, coding sequence variant, intron variant
rs193922126	AATTTGGA>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs193922128	TCTG>-	Likely-pathogenic, pathogenic	Frameshift variant, coding sequence variant
rs193922129	T>C	Likely-pathogenic	Splice acceptor variant
rs193922131	C>T	Likely-pathogenic	Splice acceptor variant
rs193922132	T>C	Likely-pathogenic	Splice acceptor variant
rs193922133	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs782519139	C>A,T	Likely-pathogenic	Coding sequence variant, synonymous variant, missense variant
rs864321659	C>T	Pathogenic	Intron variant
rs864321660	TTCT>-	Pathogenic	Frameshift variant, coding sequence variant
rs864321661	TT>-	Pathogenic	Intron variant
rs864321662	C>G	Pathogenic	Splice acceptor variant
rs864321663	T>C	Pathogenic	Splice acceptor variant
rs864321664	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs864321665	->T	Pathogenic	Frameshift variant, coding sequence variant
rs886039321	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs886039555	T>C	Pathogenic	Splice acceptor variant
rs886039657	G>A	Pathogenic	Stop gained, coding sequence variant
rs886041148	->T	Pathogenic	Frameshift variant, coding sequence variant
rs886041149	G>A,C	Uncertain-significance, pathogenic	Missense variant, stop gained, coding sequence variant
rs886041473	G>A	Pathogenic	Stop gained, coding sequence variant
rs1057517709	A>T	Pathogenic	Missense variant, coding sequence variant, intron variant
rs1057517710	C>T	Pathogenic	Missense variant, coding sequence variant, intron variant
rs1057519825	C>G	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, intron variant
rs1057519826	A>T	Not-provided, likely-pathogenic	Missense variant, coding sequence variant, intron variant
rs1057520045	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057520578	C>G,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057520612	A>T	Pathogenic	Coding sequence variant, stop gained
rs1057520682	G>A,C,T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1057521116	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1057521814	G>A,C	Likely-pathogenic, pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1064793859	C>T	Pathogenic	Splice donor variant
rs1064794285	CCT>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs1064794904	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1064796809	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1064796836	C>T	Pathogenic	Coding sequence variant, stop gained, intron variant
rs1131691354	C>A,T	Likely-pathogenic, pathogenic	Intron variant
rs1555977339	C>T	Pathogenic	Missense variant, coding sequence variant
rs1555977341	A>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1555977461	A>G	Pathogenic	Missense variant, coding sequence variant
rs1555977474	C>A,T	Pathogenic, likely-pathogenic	Stop gained, missense variant, coding sequence variant
rs1555977580	CACCT>TTTC	Pathogenic	Intron variant, coding sequence variant, splice donor variant
rs1555977592	AACA>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555977598	T>A	Pathogenic	Splice acceptor variant
rs1555977811	G>A	Pathogenic	Intron variant, stop gained, coding sequence variant
rs1555978024	C>G	Pathogenic	Intron variant, missense variant, coding sequence variant
rs1555978197	G>A	Pathogenic	Missense variant, coding sequence variant
rs1555978277	C>T	Pathogenic	Missense variant, coding sequence variant
rs1555978412	ATAGTTAC>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1555978777	A>T	Likely-pathogenic	Splice donor variant
rs1555978891	G>T	Pathogenic	Stop gained, coding sequence variant
rs1555980049	C>T	Pathogenic, likely-pathogenic	Stop gained, coding sequence variant
rs1555980796	G>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1555980799	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555980866	TTAC>-	Pathogenic	Intron variant, splice donor variant
rs1555980875	T>C	Pathogenic	Missense variant, coding sequence variant
rs1555980888	G>A	Pathogenic	Stop gained, coding sequence variant
rs1569291215	C>A	Pathogenic	Splice donor variant
rs1569291644	A>G	Pathogenic	Coding sequence variant, missense variant, intron variant
rs1569292021	G>A	Likely-pathogenic	Coding sequence variant, stop gained, intron variant
rs1569292214	A>T	Pathogenic	Coding sequence variant, missense variant
rs1569292649	C>T	Pathogenic	Splice donor variant
rs1569292774	->A	Pathogenic	Coding sequence variant, frameshift variant
rs1569292810	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1569292813	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1569292818	AC>-	Pathogenic	Coding sequence variant, frameshift variant
rs1569293252	C>A	Likely-pathogenic	Splice donor variant
rs1569293253	->ATGTAGCT	Pathogenic	Coding sequence variant, frameshift variant
rs1569295678	G>T	Pathogenic	Coding sequence variant, stop gained
rs1569296295	C>T	Likely-pathogenic	Coding sequence variant, synonymous variant
rs1603001771	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1603001805	C>T	Pathogenic	Coding sequence variant, stop gained
rs1603001846	C>G	Pathogenic	Splice acceptor variant
rs1603002367	->TA	Pathogenic	Coding sequence variant, frameshift variant
rs1603002421	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1603004481	G>A	Pathogenic	Coding sequence variant, stop gained, intron variant
rs1603005060	T>A	Likely-pathogenic	Intron variant
rs1603005073	C>A	Pathogenic	Coding sequence variant, stop gained, intron variant
rs1603005139	C>T	Pathogenic	Coding sequence variant, stop gained, intron variant
rs1603005659	T>C	Likely-pathogenic	Splice acceptor variant, intron variant
rs1603007888	A>T	Pathogenic	Coding sequence variant, stop gained
rs1603007942	C>T	Pathogenic	Splice acceptor variant
rs1603008329	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1603008349	C>T	Pathogenic	Coding sequence variant, stop gained
rs1603008381	->A	Pathogenic	Coding sequence variant, frameshift variant
rs1603008449	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1603009890	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1603010333	GGCAGCCCATAGCATTT>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1603017538	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1603019535	G>A	Pathogenic	Coding sequence variant, stop gained
rs1603019594	TCT>-	Pathogenic, uncertain-significance	Coding sequence variant, inframe deletion
rs1603019780	T>C	Likely-pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001128	hsa-miR-346	Luciferase reporter assay	19342689
MIRT001128	hsa-miR-346	qRT-PCR	19342689
MIRT001128	hsa-miR-346	Northern blot	19342689
MIRT001128	hsa-miR-346	Western blot	19342689
MIRT731682	hsa-miR-210-3p	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731682	hsa-miR-210-3p	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731683	hsa-miR-425-5p	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731683	hsa-miR-425-5p	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731684	hsa-miR-1253	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731684	hsa-miR-1253	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731685	hsa-miR-4269	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731685	hsa-miR-4269	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731686	hsa-miR-4667-3p	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT731686	hsa-miR-4667-3p	ChIP-seq, Immunoblot, Luciferase reporter assay, Western blot	27756747
MIRT1944816	hsa-miR-147b	CLIP-seq
MIRT1944817	hsa-miR-210	CLIP-seq
MIRT1944818	hsa-miR-4786-3p	CLIP-seq
MIRT2183242	hsa-miR-329	CLIP-seq
MIRT2183243	hsa-miR-362-3p	CLIP-seq
MIRT2183244	hsa-miR-4514	CLIP-seq
MIRT2183245	hsa-miR-4692	CLIP-seq
MIRT2183246	hsa-miR-4742-5p	CLIP-seq
MIRT2183247	hsa-miR-513a-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
SP1	Unknown	10362515
SP3	Unknown	10362515
SPI1	Unknown	10362515

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001805	Process	Positive regulation of type III hypersensitivity	IEA
GO:0001812	Process	Positive regulation of type I hypersensitivity	IEA
GO:0001818	Process	Negative regulation of cytokine production	IEA
GO:0002250	Process	Adaptive immune response	TAS	19290921
GO:0002344	Process	B cell affinity maturation	IEA
GO:0002553	Process	Histamine secretion by mast cell	IEA
GO:0002721	Process	Regulation of B cell cytokine production	TAS	19290921
GO:0002755	Process	MyD88-dependent toll-like receptor signaling pathway	TAS
GO:0002902	Process	Regulation of B cell apoptotic process	TAS	19290921
GO:0004713	Function	Protein tyrosine kinase activity	EXP	7518558
GO:0004713	Function	Protein tyrosine kinase activity	IBA	21873635
GO:0004713	Function	Protein tyrosine kinase activity	TAS	11913944
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	TAS	19290921
GO:0005515	Function	Protein binding	IPI	8892607, 9012831, 9571151, 11788586, 15046600, 15539407, 16969585, 19214191, 22366891, 22939624, 25825872, 25910212
GO:0005524	Function	ATP binding	TAS	11913944
GO:0005547	Function	Phosphatidylinositol-3,4,5-trisphosphate binding	IDA	17823121
GO:0005634	Component	Nucleus	TAS	19290921
GO:0005737	Component	Cytoplasm	TAS	15046600
GO:0005829	Component	Cytosol	IDA	17823121
GO:0005829	Component	Cytosol	TAS	19290921
GO:0005886	Component	Plasma membrane	IDA	17823121
GO:0005886	Component	Plasma membrane	TAS	19290921
GO:0006468	Process	Protein phosphorylation	TAS	11913944
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	IEA
GO:0007498	Process	Mesoderm development	TAS	8013627
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IDA	11606584
GO:0019722	Process	Calcium-mediated signaling	TAS	15046600
GO:0030889	Process	Negative regulation of B cell proliferation	IEA
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0034614	Process	Cellular response to reactive oxygen species	IEA
GO:0035556	Process	Intracellular signal transduction	TAS	11913944
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042113	Process	B cell activation	TAS	19290921
GO:0042802	Function	Identical protein binding	IPI	11577348
GO:0045087	Process	Innate immune response	TAS	19290921
GO:0045121	Component	Membrane raft	IDA	15046600
GO:0045579	Process	Positive regulation of B cell differentiation	TAS	19290921
GO:0046777	Process	Protein autophosphorylation	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048469	Process	Cell maturation	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0050853	Process	B cell receptor signaling pathway	TAS	19290921
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	TAS	19290921
GO:0071226	Process	Cellular response to molecule of fungal origin	IEA
GO:0097190	Process	Apoptotic signaling pathway	TAS	8688094
GO:0098761	Process	Cellular response to interleukin-7	IEA

Other IDs

• MIM: 300300
• HGNC: 1133
• e!Ensembl: ENSG00000010671

Protein

• UniProt ID: Q06187
• Protein name: Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase)
• Protein function: Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubM
• PDB: 1AWW, 1AWX, 1B55, 1BTK, 1BWN, 1K2P, 1QLY, 2GE9, 2Z0P, 3GEN, 3K54, 3OCS, 3OCT, 3P08, 3PIX, 3PIY, 3PIZ, 3PJ1, 3PJ2, 3PJ3, 4NWM, 4OT5, 4OT6, 4OTF, 4OTQ, 4OTR, 4RFY, 4RFZ, 4RG0, 4RX5, 4YHF, 4Z3V, 4ZLY, 4ZLZ, 5BPY, 5BQ0, 5FBN, 5FBO, 5J87, 5JRS, 5KUP, 5P9F, 5P9G, 5P9H, 5P9I, 5P9J, 5P9K, 5P9L, 5P9M, 5T18, 5U9D
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00169	PH	4 → 133	PH domain	Domain
  PF00779	BTK	141 → 170	BTK motif	Motif
  PF00018	SH3_1	220 → 266	SH3 domain	Domain
  PF00017	SH2	281 → 362	SH2 domain	Domain
  PF07714	PK_Tyr_Ser-Thr	402 → 651	Protein tyrosine and serine/threonine kinase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Predominantly expressed in B-lymphocytes.
• Sequence:

  MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEK
  ITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEEL
  RKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSS
  HRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDE
  YFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGK
  EGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELIN
  YHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGK
  WRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG
  CLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDF
  GLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYER
  FTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES

• Sequence length: 659

Pathways

KEGG:

NF-kappa B signaling pathway
Osteoclast differentiation
Platelet activation
B cell receptor signaling pathway
Fc epsilon RI signaling pathway
Epstein-Barr virus infection
Primary immunodeficiency

Reactome:

ER-Phagosome pathway
MyD88:MAL(TIRAP) cascade initiated on plasma membrane
Regulation of actin dynamics for phagocytic cup formation
DAP12 signaling
FCERI mediated Ca+2 mobilization
G alpha (q) signalling events
G alpha (12/13) signalling events
MyD88 deficiency (TLR2/4)
IRAK4 deficiency (TLR2/4)
RHO GTPases Activate WASPs and WAVEs
G beta:gamma signalling through BTK
FCGR3A-mediated phagocytosis
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

Associated diseases

Causal
Disease term	Disease name	dbSNP ID	References
Agammaglobulinemia	Agammaglobulinemia, AGAMMAGLOBULINEMIA 1, AUTOSOMAL RECESSIVE	rs2134166251, rs128620183, rs128620185, rs128621193, rs128621201, rs128621204, rs121912424, rs267606711, rs376256147, rs281865422, rs1600631593, rs1555843601, rs267606871, rs879255271, rs2142904392, rs1555976766, rs1555977461, rs1555977580, rs1555977592, rs1555977598, rs1555978024, rs1555978197, rs1555978277, rs1555978891, rs1555980049, rs1555980799, rs1555980866, rs1554906579, rs1568801716, rs1565638431, rs2095906547, rs2095906404	10352268, 15142874
Agammaglobulinemia with growth hormone deficiency, x-linked	X-linked agammaglobulinemia with growth hormone deficiency	rs128620183, rs128620187, rs128620188, rs864321659, rs128620185, rs128620186, rs864321660, rs864321662, rs864321664, rs864321665, rs128621192, rs128621193, rs128621194, rs128621197, rs128621201, rs128621202, rs128621204, rs128621207, rs104894770, rs193922128, rs193922129, rs193922131, rs193922132, rs886039555, rs886041149, rs886041148, rs1064793859, rs1555977339, rs1555980875, rs1555977592, rs1555978277, rs1555980049, rs1569295678, rs1555977474, rs1569291644, rs1569292021, rs1569292810, rs1569296295, rs1603019594, rs1569293252, rs1603001805, rs1603002367, rs1057521814, rs1603002421, rs1603004481, rs1603004514, rs1603005073, rs1603005139, rs1603008349, rs1603008449, rs1603009890, rs1603017538, rs1603019535, rs1603020228, rs1603001846, rs1603007942, rs1603008381, rs1603005659, rs1926352588, rs1926378381, rs1926503277, rs1926711302, rs1926977049, rs1927172387, rs1926404279, rs1926404536	9554752, 8938104, 7880320, 11472359, 11742281, 7849721, 12655572, 27980540, 19904586, 11668622, 18677443, 22139958, 8695804, 23424595, 7633429, 9445504, 8013627, 15661032, 9260159, 20529312, 10737994, 26350204, 12217331, 8939985, 16951917, 7711734, 28359783, 12204007, 9545398, 9143921, 17765309, 12405164
Agammaglobulinemia, x-linked	X-linked agammaglobulinemia	rs128620183, rs128620184, rs128620187, rs128620188, rs128620185, rs128620186, rs128620189, rs864321660, rs864321661, rs864321662, rs864321663, rs128621190, rs864321664, rs864321665, rs1569293253, rs1569292813, rs128621191, rs128621192, rs128621193, rs1569292649, rs128621194, rs128621195, rs128621196, rs2147430166, rs2147429013, rs128621198, rs128621199, rs41310709, rs128621201, rs128621202, rs2147425836, rs1569291215, rs128621204, rs128621205, rs128621206, rs128621207, rs128621208, rs128621209, rs128621210, rs128622211, rs2147423959, rs128622212, rs104894770, rs1569292818, rs1131691354, rs193922124, rs193922125, rs193922126, rs193922128, rs193922129, rs193922131, rs193922132, rs886041148, rs1064793859, rs1555977339, rs1555977592, rs1555978277, rs1555980049, rs1555980796, rs1555978412, rs1555978777, rs1569292774, rs1569291644, rs1569292214, rs1569292021, rs1569292810, rs1569296295, rs1603019594, rs1569293252, rs1603001805, rs1603007942, rs1603001771, rs1603008381, rs782519139, rs1603005659	27512878, 9445504, 7711734, 7849697, 10220140, 15661032, 10678660, 10737994, 12655572, 7627183, 9260159, 7849721, 8162018, 19904586, 26350204, 7880320, 7633429, 7633420, 8695804, 11742281, 9016530, 8013627, 19039656, 8162056, 16160918, 8634718, 7849006, 11102984, 12405164, 11809909, 7809124, 9280283, 8834236, 9545398, 10887125, 16712653, 21397315, 8594569, 8723128, 7897635, 10612838
Anemia	Anemia	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Arthritis	Arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470
Breast adenocarcinoma	Breast adenocarcinoma	rs28934874, rs112445441, rs121913279, rs121913286, rs104886003, rs121434592
Breast cancer	Malignant neoplasm of breast	rs587776547, rs1137887, rs137853007, rs587776650, rs80359351, rs80359714, rs121917783, rs104886456, rs121964878, rs80359874, rs80357868, rs80357508, rs387906843, rs80357569, rs80358158, rs80357524, rs80357115, rs80357945, rs80357729, rs80357609, rs80357259, rs80357981, rs80358063, rs80357389, rs80356862, rs80359876, rs80357580, rs80358053, rs80358089, rs80187739, rs397507241, rs80358069, rs80357590, rs80357284, rs80357941, rs80359261, rs80359272, rs80359276, rs276174813, rs80358474, rs80359316, rs1555282969, rs80359388, rs80359499, rs80359505, rs80359520, rs80359526, rs80359533, rs56253082, rs80358824, rs80359554, rs80359636, rs80359651, rs80359659, rs80359011, rs80359012, rs80359013, rs80359718, rs397507410, rs81002812, rs80359730, rs80359152, rs80359159, rs397507419, rs28897759, rs80359211, rs80359775, rs397514577, rs397507584, rs80358435, rs80358456, rs80359340, rs80359343, rs80359365, rs80358579, rs397507670, rs80358593, rs80359406, rs80359444, rs80359454, rs276174853, rs276174854, rs80359483, rs80359537, rs80358815, rs80358843, rs80359558, rs80359560, rs80359594, rs80358893, rs28897743, rs397507900, rs397507906, rs397507918, rs80358971, rs80358981, rs397507941, rs80359030, rs80359035, rs41293511, rs397507396, rs81002806, rs80359112, rs397508006, rs81002893, rs45580035, rs80359760, rs397508051, rs80359772, rs4987049, rs80359777, rs80357770, rs397508867, rs62625303, rs397508874, rs80357506, rs80357287, rs273898674, rs80358042, rs80358083, rs80357058, rs41286296, rs80357960, rs80356945, rs80357223, rs386134270, rs80358116, rs80357856, rs80357424, rs397509050, rs80357485, rs80357966, rs397509067, rs80357310, rs80356866, rs80357260, rs80357437, rs80358023, rs80358086, rs80357133, rs80356993, rs80357997, rs80357239, rs80357227, rs397509243, rs80356969, rs80356959, rs63750617, rs63751319, rs587779315, rs200640585, rs398122546, rs80357543, rs398122687, rs80359328, rs398122779, rs398122783, rs62517194, rs80358029, rs515726060, rs180177103, rs180177111, rs180177133, rs587776527, rs180177135, rs180177136, rs515726117, rs587779813, rs587779909, rs587780024, rs587780100, rs28909982, rs121908698, rs180177100, rs587780210, rs587780240, rs587780639, rs587781269, rs587781353, rs587781471, rs587781658, rs587781697, rs587781730, rs587781894, rs587781948, rs587782005, rs587782011, rs200928781, rs587781558, rs370228071, rs587782245, rs587782401, rs180177110, rs587782504, rs72552322, rs587782531, rs587782620, rs587782680, rs587782774, rs587782818, rs730881411, rs730881389, rs564652222, rs397507768, rs587776419, rs730881868, rs730881940, rs56383036, rs758972589, rs201089102, rs730881348, rs786202608, rs786201886, rs786203318, rs786203775, rs786203714, rs786202033, rs750621215, rs786203884, rs786203650, rs772821016, rs863224521, rs864622223, rs864622655, rs375699023, rs876659572, rs768362387, rs876659535, rs876658957, rs483353072, rs876659435, rs267608041, rs876661113, rs730881369, rs878853535, rs772228129, rs878855122, rs760551339, rs80359596, rs397509222, rs886039630, rs886039683, rs886040828, rs587781799, rs886040374, rs886040649, rs397507967, rs878854957, rs886040043, rs1057517589, rs1060502769, rs866380588, rs863224765, rs1064793243, rs747563556, rs1555074976, rs1064795885, rs753961188, rs1064794708, rs869312772, rs1064793887, rs1131690820, rs1135401928, rs1135401868, rs1135401859, rs1553370324, rs397507630, rs1555283160, rs1555283251, rs1555283262, rs1555283361, rs1555286298, rs1555288462, rs886040950, rs1555289566, rs776323117, rs80357123, rs1555579627, rs1555580697, rs80358054, rs1555593302, rs1328985852, rs763470424, rs1555139694, rs878854697, rs1555461217, rs1555461765, rs774684620, rs766416564, rs1554558613, rs1305740166, rs1555461460, rs1555461407, rs1555461586, rs1555567202, rs1555607022, rs1555069815, rs1442299125, rs1474786480, rs1555084947, rs1555457867, rs141087784, rs1482641121, rs1564830522, rs1565469955, rs1565503137, rs864622613, rs755263466, rs757679199, rs1593903166, rs1597801649, rs1603293306, rs879253880, rs80358754, rs1597062038, rs45494092, rs1603275367, rs887358871, rs1597091518, rs1966967065, rs1064793049, rs2082872908, rs2085078278, rs2072475243
Breast carcinoma	Breast Carcinoma	rs80359671, rs11540652, rs28934575, rs28897672, rs137886232, rs193922376, rs80357783, rs80359306, rs80359405, rs80359507, rs80359598, rs80358429, rs397507683, rs397515636, rs80359451, rs397507859, rs80359709, rs80359742, rs80359205, rs80357627, rs80357004, rs80357571, rs80357767, rs80357653, rs80358086, rs80357608, rs28897696, rs41293465, rs146650273, rs63751017, rs63750617, rs63750726, rs63750199, rs63749848, rs398122618, rs398122653, rs397509211, rs80357791, rs121912666, rs587778541, rs121908698, rs536907995, rs587781302, rs140342925, rs587781506, rs587782652, rs587782849, rs587783057, rs139770721, rs374950566, rs786202800, rs863224451, rs377153250, rs747727055, rs876658804, rs780001540, rs760815829, rs878854926, rs775248597, rs886040658, rs886040192, rs786203523, rs886040319, rs397508006, rs587782011, rs1060502772, rs1555461727, rs1553333072, rs1114167702, rs1257401983, rs886040950, rs1060502759, rs774684620, rs142947311, rs1555580883, rs748513310, rs376170600, rs863224499, rs1593909229, rs748453607, rs1294578913, rs1574737047, rs1593909960, rs2081922847, rs2082559544, rs2053694038
Hearing loss	Sensorineural Hearing Loss (disorder)	rs267607135, rs267606855, rs779841884, rs267606854, rs28942097, rs121908073, rs121908076, rs74315289, rs121908144, rs111033313, rs74315437, rs121908348, rs121908349, rs121908350, rs397515359, rs180177151, rs180177154, rs180177153, rs35689081, rs35887622, rs80338944, rs104894396, rs104894398, rs80338947, rs80338948, rs80338942, rs104894402, rs104894403, rs80338945, rs28931594, rs80338940, rs80338941, rs80356590, rs80338950, rs387906706, rs387906707, rs387906708, rs398122848, rs387907016, rs587776894, rs387907088, rs397515411, rs370965183, rs398122930, rs199897298, rs111033187, rs111033448, rs199606180, rs111033284, rs397516413, rs111033305, rs111033220, rs111033256, rs111033297, rs111033253, rs104894408, rs111033295, rs397516874, rs76434661, rs111033335, rs397517323, rs111033247, rs367928692, rs374793617, rs143939430, rs397515605, rs80338939, rs200656442, rs779748859, rs587781261, rs587781262, rs143343083, rs200147906, rs730880338, rs797044491, rs146281367, rs756484720, rs869025593, rs201306709, rs540895576, rs777777359, rs879255246, rs1554358720, rs142498437, rs377145777, rs1057517519, rs779077039, rs952741388, rs1060499797, rs764139009, rs1060499590, rs1064794012, rs1064797115, rs756790858, rs775633137, rs1554952443, rs1554952193, rs782063761, rs1199012623, rs756147087, rs1555648043, rs1555661490, rs1553196233, rs781546107, rs111033190, rs775428246, rs782539587, rs537227442, rs148695069, rs1554835827, rs953422571, rs1554834186, rs1554834161, rs1554835103, rs1554577339, rs1554577402, rs768471577, rs782279338, rs781951909, rs998045226, rs375759781, rs755804651, rs1557458426, rs767797828, rs538027448, rs1559366084, rs367688416, rs1558480402, rs1558490542, rs1559870857, rs1560690591, rs1561299289, rs1562817224, rs1562817529, rs1562822565, rs1562835391, rs1564113368, rs1564554255, rs773851192, rs1564555240, rs761261855, rs1564805114, rs1565522273, rs1565127413, rs781790246, rs1565430886, rs1565469959, rs746667217, rs1565819402, rs1565855932, rs150529554, rs1567939793, rs201866631, rs754472294, rs1559372512, rs1558464965, rs1558488902, rs775062249, rs1226171550, rs1561590396, rs765574676, rs762876554, rs757327146, rs1564949059, rs1565519673, rs368050948, rs1565541888, rs781989117, rs1565402473, rs750358148, rs1386887007, rs1209665716, rs1567641234, rs1237955948, rs1569042782, rs752672077, rs146689036, rs1560070780, rs149712664, rs1564556995, rs762226905, rs773573968, rs1568528171, rs1198256157, rs377267777, rs370564476, rs1577876794, rs747787770, rs759432278, rs1043716893, rs1581138934, rs2033773650, rs1421964916, rs771766431, rs780917129, rs1895773215, rs1895769400, rs761543680, rs1565920060
Isolated somatotropin deficiency	Isolated somatotropin deficiency	rs797044450, rs71640277, rs863223306, rs2144738731, rs863223307, rs2144739370, rs863223309, rs863223310, rs137853223, rs2144739380, rs2144739391
Lung carcinoma	Large cell carcinoma of lung	rs1805076, rs121909071, rs121913530, rs112445441, rs121913529, rs121913535, rs121913297, rs121913279, rs104886003, rs397516975, rs11554290, rs121913364, rs121913351, rs121913369, rs121913355, rs121912470, rs121913273, rs121913281, rs121913348, rs727503093, rs121913353, rs397516890, rs397516896, rs121913378, rs397516897, rs397516977, rs397516978, rs397516979, rs397516980, rs397516981, rs397516982, rs121913240, rs17851045, rs397517086, rs121913428, rs397517094, rs397517098, rs397517106, rs121913465, rs397517108, rs397517111, rs397517112, rs397517114, rs397517116, rs1554350366, rs397517127, rs397517200, rs397517202, rs121913283, rs121913370, rs121913357, rs727503106, rs121913238, rs727503108, rs397517040, rs397516976, rs1555618025, rs1057519729, rs1584238193
Neutropenia	Neutropenia	rs879253882

Unknown
Disease term	Disease name	Evidence	References	Source
Osteomyelitis	Osteomyelitis			ClinVar
Otitis media	Otitis Media, Chronic otitis media			ClinVar
Hypogammaglobulinemia	short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia			GenCC
Isolated Growth Hormone Deficiency	isolated growth hormone deficiency type III			GenCC

Associations from Text Mining
Disease Name	Relationship Type	References
Achondroplasia and Swiss type agammaglobulinemia	Associate	10792386, 11472359, 11555397, 12823285, 15932514, 17900300, 17932028, 21488866, 23549506, 24074005, 28990652, 31378960, 31830942, 8758136, 9030858, 9192269, 9201297, 9218782, 9486400, 9753052, 9778529
Achondroplasia and Swiss type agammaglobulinemia	Inhibit	10844531
Adenocarcinoma	Associate	32509861
Adenocarcinoma of Lung	Associate	34187403, 35675043, 35733175, 38071755
Agammaglobulinemia	Associate	10859027, 11686883, 12958074, 30619340, 36056138, 37904676
Anemia Hemolytic Autoimmune	Associate	31392938
Arthritis Psoriatic	Associate	37669474
Arthritis Rheumatoid	Associate	32365786, 33389462, 38350168, 40594127
Asthma	Associate	24383975
Atrial Fibrillation	Inhibit	38211337
Autoimmune Diseases	Associate	31616406, 36521376
Bacterial Infections	Associate	11206059
Blood Platelet Disorders	Associate	29383704, 32986868
Breast Neoplasms	Associate	23913792, 33760219
Bronchiectasis	Associate	33013854
Bronchiolitis Obliterans	Associate	35382780
Bronchopneumonia	Associate	24383975
Bruton type agammaglobulinemia	Associate	10196129, 10556826, 10561498, 10590061, 10688822, 10859027, 10887125, 10930571, 11206059, 11433390, 11577078, 11686883, 11877289, 12370281, 12487187, 12958074, 15466623, 16862044, 16913189, 17090647, 18306466, 19268935, 20721470, 21039741, 21238622, 21609956, 21738355, 21905506, 22053596, 22289994, 22378381, 22927353, 23549506, 24383975, 24658450, 24885015, 25316352, 27512878, 28422989, 28754963, 29424453, 29503650, 30147693, 30559311, 30564228, 31481959, 31510946, 32117230, 32385234, 32552675, 32615664, 33013854, 33224144, 33235662, 33261572, 33377626, 33453577, 33876953, 34252140, 34863924, 35288819, 35382780, 37197664, 37809070, 37904676, 39434672, 40225173, 7519238, 7629518, 7929028, 8013627, 8090769, 8594569, 8644706, 8695804, 8898377, 9016530, 9106525, 9260159, 9280283, 9399844, 9414287, 9427714, 9446655, 9545398, 9880544
Bruton type agammaglobulinemia	Inhibit	10480303
Burkitt Lymphoma	Associate	28474336, 9880544
Carcinoma	Associate	35732327
Carcinoma Hepatocellular	Associate	33013854
Carcinoma Non Small Cell Lung	Inhibit	37638060
Carcinoma Renal Cell	Associate	23782158
Carotid Stenosis	Associate	37644056
Cell Transformation Neoplastic	Associate	37685940
Chromosome 12 12p trisomy	Associate	34189564
Chromosome Deletion	Associate	33013854
Clinical Deterioration	Associate	37314786
Colorectal Neoplasms	Associate	26804170
Common Variable Immunodeficiency	Associate	10844531, 11472409, 11520777
COVID 19	Associate	33226337, 33441177, 34907210, 36208028, 36676732, 36736734
Depressive Disorder	Associate	36634823
Diabetes Mellitus	Associate	36736734
Diabetes Mellitus Type 2	Associate	36736734, 38034011
Disease Progression	Associate	37314786, 37955424
Drug Related Side Effects and Adverse Reactions	Associate	28061447, 28573668
Drug Related Side Effects and Adverse Reactions	Inhibit	40076826
Dwarfism Pituitary	Associate	8013627
Dysgammaglobulinemia	Associate	19903677
Dystonia	Inhibit	33013854
Ecthyma	Associate	30559311
Evans Syndrome	Associate	31392938
Failure to Thrive	Associate	24383975
Fibrosis	Associate	35382780
Genetic Diseases Inborn	Associate	10792386, 11686883, 32615664
Genetic Diseases X Linked	Associate	8090769
Genetic Predisposition to Disease	Associate	30508305
Glioma	Associate	34645618, 34784299, 38381384
Glomerulonephritis IGA	Stimulate	33389462
Graves Ophthalmopathy	Associate	35980936
Graves Ophthalmopathy	Stimulate	36521376
Hashimoto Disease	Associate	40022006
Hearing Loss Sensorineural	Associate	33013854
Hemolysis	Associate	31392938
Hemorrhage	Associate	32986868
Hemorrhagic Disorders	Inhibit	38211337
Hidradenitis Suppurativa	Associate	32853177
Humoral Hypercalcemia Of Malignancy	Associate	23549506
Hyper IgM Immunodeficiency Syndrome	Associate	30619340, 33377626
Hyper IgM Immunodeficiency Syndrome Type 1	Associate	15358621
Hypogammaglobulinemia X Linked	Associate	8364206
IgG Deficiency	Associate	19903677
Immune System Diseases	Associate	26017814, 37197664, 37325673
Immunologic Deficiency Syndromes	Associate	18252213, 34975878, 8644706, 9260159
Infections	Associate	15932514, 23230296, 24383975, 33453577
Inflammation	Associate	18025155, 36267464, 38254312
Inflammation	Inhibit	35303161
Invasive Pneumococcal Disease Recurrent Isolated 2	Associate	33225392
Invasive Pulmonary Aspergillosis	Associate	35326454
Kniest Like Dysplasia with Pursed Lips and Ectopia Lentis	Associate	33235662
Kotzot Richter syndrome	Associate	26182309, 30508305
Leukemia	Associate	16141323, 33226337, 40516328, 9880544
Leukemia B Cell	Associate	20054396, 27799566, 31123343, 31378960, 33226337, 8695804, 9778529, 9880544
Leukemia Biphenotypic Acute	Associate	37095455
Leukemia Hairy Cell	Associate	24697238
Leukemia Lymphocytic Chronic B Cell	Associate	23782158, 25170122, 25673699, 25829398, 26182309, 26641137, 26717038, 27602755, 27626698, 28049639, 28154084, 28212557, 28373262, 28418267, 29301866, 30018078, 30508305, 30692684, 31243043, 31876911, 32054731, 32202637, 32244251, 33684943, 33735912, 33875521, 34187466, 34500472, 34861696, 34912339, 35196427, 35326454, 35743155, 35759759, 35901282, 36287227, 36485152, 36696464, 37174695, 37227160, 37314786, 38055246, 38139452, 38301010, 40179394
Leukemia Lymphocytic Chronic B Cell	Inhibit	40076826
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	23719297, 36272407
Leukemia Myeloid Acute	Associate	24307721, 25605370, 26292723, 32915972, 35624145
Leukemia Prolymphocytic	Associate	28049639
Leukemia Prolymphocytic T Cell	Associate	27199251, 29317636, 31821686, 39794120
Leukoencephalopathies	Associate	38345145
Light Fixation Seizure Syndrome	Associate	15358621, 24074005
Lung Diseases	Associate	35382780
Lung Injury	Associate	33441177
Lupus Nephritis	Associate	33389462
Lymphatic Diseases	Associate	28424405
Lymphatic Metastasis	Stimulate	39925800
Lymphohistiocytosis Hemophagocytic	Associate	31481959, 33013854
Lymphoma	Associate	28619981, 33226337
Lymphoma B Cell	Associate	26017814, 28036258, 28424405, 30337526, 32385234, 34750354, 35326454, 35641438, 37074239, 38301010
Lymphoma Follicular	Associate	16835385, 24357726, 28064239, 29074501, 33419778, 33579791
Lymphoma Large B Cell Diffuse	Associate	23360303, 26540570, 28178345, 30534553, 31123343, 32127472, 32585766, 32926124, 34795418, 35757723, 36871027, 36897912, 37184294, 37364001
Lymphoma Mantle Cell	Associate	23360303, 23940282, 24957109, 25082755, 25797245, 26285204, 27127301, 27157620, 27713153, 31534006, 31808882, 34174847, 34508613, 35266562, 35561299, 35561314, 35789260, 36719376, 37562004, 38072625, 39394843
Lymphoma Non Hodgkin	Associate	38381384
Mastocytosis Systemic	Associate	21680801
Melanoma	Associate	33177155
Mohr Tranebjaerg syndrome	Associate	33013854, 36056138
Multiple Myeloma	Associate	25565020, 34792571, 35985681
Multiple Sclerosis	Associate	35303161, 35852869, 38254312
Multiple Sclerosis Relapsing Remitting	Stimulate	35852869
Neoplasm Metastasis	Associate	33760219, 39925800
Neoplasm Residual	Associate	33188997
Neoplasms	Associate	16835385, 21680801, 23782158, 23913792, 26017814, 26285204, 28178345, 28830912, 29869556, 30337526, 32114502, 33054082, 33441177, 34116165, 34508613, 34645618, 36521376, 36897912, 37074239, 37638060, 37685940, 39925800
Neurofibromatosis 1	Associate	12487187
Neutropenia	Inhibit	38211337
Organizing Pneumonia	Associate	34907210
Otitis Media	Associate	24383975
Ovarian Neoplasms	Associate	39925800
Pancreatic Neoplasms	Associate	32114502
Parkinson Disease	Associate	36634823
Peri Implantitis	Associate	36267464
Plasmablastic Lymphoma	Associate	34714908
Polycythemia	Associate	12515724
Polysaccharide Storage of Unusual	Associate	31378960
Precursor T Cell Lymphoblastic Leukemia Lymphoma	Associate	26292723
Primary Immunodeficiency Diseases	Associate	22927353, 26162572, 30564228, 33632949, 8013627
Prostatic Neoplasms	Associate	26383180
Pseudomonas Infections	Associate	33013854
Recurrence	Associate	31830942
Respiratory Distress Syndrome	Associate	23239500
Rupture	Associate	31329646
Sarcoma Ewing	Associate	31392938
Sepsis	Associate	30559311
Severe Combined Immunodeficiency	Associate	22927353, 30564228
Sexual Dysfunction Physiological	Associate	28623282
Sjogren's Syndrome	Associate	35563492
Squamous Cell Carcinoma of Head and Neck	Associate	37685940
Substance Related Disorders	Associate	32585766
Tertiary Lymphoid Structures	Associate	37638060
Thrombosis	Associate	29383704
Urinary Bladder Neoplasms	Associate	40594127
Virus Diseases	Associate	17932028
Waldenstrom Macroglobulinemia	Associate	23836557, 27143257, 28235842, 28548645, 29869556, 34253577, 36282673, 38211337
Wiskott Aldrich Syndrome	Associate	22927353
Wiskott Aldrich Syndrome	Inhibit	27330000
X Linked Combined Immunodeficiency Diseases	Associate	8982277
Young Syndrome	Associate	33013854