SH2D1A (SH2 domain containing 1A)

Gene

• Entrez ID: 4068
• Gene name: SH2 domain containing 1A
• Gene symbol: SH2D1A
• Synonyms: DSHP, EBVS, IMD5, LYP, MTCP1, SAP, SAP/SH2D1A, XLP, XLPD, XLPD1
• Chromosome: X
• Chromosome location: Xq25
• Summary: This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs111033623	C>T	Pathogenic	Coding sequence variant, stop gained
rs111033624	G>C	Pathogenic	Coding sequence variant, missense variant
rs111033625	T>A,C	Pathogenic, likely-pathogenic	Terminator codon variant, stop lost
rs111033626	C>T	Pathogenic	Coding sequence variant, missense variant
rs111033627	C>T	Pathogenic	Coding sequence variant, missense variant
rs111033628	C>T	Pathogenic	Coding sequence variant, stop gained
rs111033629	G>T	Pathogenic	Initiator codon variant, missense variant
rs111033630	G>T	Pathogenic	Coding sequence variant, missense variant
rs587777612	G>C	Pathogenic	Intron variant
rs1556619319	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1556620697	C>G	Likely-pathogenic	Intron variant
rs1556620698	C>A	Pathogenic	Stop gained, coding sequence variant
rs1556620706	G>A	Pathogenic	Stop gained, coding sequence variant
rs1569527111	A>G	Pathogenic	Coding sequence variant, missense variant
rs1603236465	C>T	Pathogenic	5 prime UTR variant
rs1603238847	G>T	Pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT021557	hsa-miR-142-3p	Microarray	17612493
MIRT722321	hsa-miR-6760-3p	HITS-CLIP	19536157
MIRT722320	hsa-miR-1208	HITS-CLIP	19536157
MIRT722319	hsa-miR-5701	HITS-CLIP	19536157
MIRT722318	hsa-miR-181b-2-3p	HITS-CLIP	19536157
MIRT722317	hsa-miR-181b-3p	HITS-CLIP	19536157
MIRT722316	hsa-miR-4420	HITS-CLIP	19536157
MIRT722315	hsa-miR-653-3p	HITS-CLIP	19536157
MIRT722314	hsa-miR-3606-3p	HITS-CLIP	19536157
MIRT722321	hsa-miR-6760-3p	HITS-CLIP	19536157
MIRT722320	hsa-miR-1208	HITS-CLIP	19536157
MIRT722319	hsa-miR-5701	HITS-CLIP	19536157
MIRT722318	hsa-miR-181b-2-3p	HITS-CLIP	19536157
MIRT722317	hsa-miR-181b-3p	HITS-CLIP	19536157
MIRT722316	hsa-miR-4420	HITS-CLIP	19536157
MIRT722315	hsa-miR-653-3p	HITS-CLIP	19536157
MIRT722314	hsa-miR-3606-3p	HITS-CLIP	19536157
MIRT1344208	hsa-miR-127-5p	CLIP-seq
MIRT1344209	hsa-miR-4795-3p	CLIP-seq
MIRT1344210	hsa-miR-582-5p	CLIP-seq
MIRT1344211	hsa-miR-1206	CLIP-seq
MIRT1344212	hsa-miR-3140-3p	CLIP-seq
MIRT1344213	hsa-miR-3607-5p	CLIP-seq
MIRT1344214	hsa-miR-4777-3p	CLIP-seq
MIRT2326147	hsa-miR-3671	CLIP-seq
MIRT2326148	hsa-miR-520d-5p	CLIP-seq
MIRT2326149	hsa-miR-524-5p	CLIP-seq
MIRT2326150	hsa-miR-556-5p	CLIP-seq
MIRT2326151	hsa-miR-935	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ATF5	Unknown	18832568

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002250	Process	Adaptive immune response	IEA
GO:0005515	Function	Protein binding	IPI	9774102, 10549287, 11389028, 11477068, 11489943, 11806999, 11823424, 12225753, 12545174, 14674764, 16920955, 20231852, 22912825, 23346089, 24642916, 24688028, 24728074, 25416956, 25910212, 26221972, 32296183, 32814053
GO:0005737	Component	Cytoplasm	IDA	9774102
GO:0005829	Component	Cytosol	TAS
GO:0006959	Process	Humoral immune response	IEA
GO:0006968	Process	Cellular defense response	IEA
GO:0007267	Process	Cell-cell signaling	IEA
GO:0045087	Process	Innate immune response	IEA
GO:0045954	Process	Positive regulation of natural killer cell mediated cytotoxicity	IEA
GO:0050776	Process	Regulation of immune response	IMP	9774102
GO:0050776	Process	Regulation of immune response	TAS
GO:0050860	Process	Negative regulation of T cell receptor signaling pathway	IDA	9774102

Other IDs

• MIM: 300490
• HGNC: 10820
• e!Ensembl: ENSG00000183918

Protein

• UniProt ID: O60880
• Protein name: SH2 domain-containing protein 1A (Duncan disease SH2-protein) (Signaling lymphocytic activation molecule-associated protein) (SLAM-associated protein) (T-cell signal transduction molecule SAP)
• Protein function: Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2. Initially it has been proposed t
• PDB: 1D1Z, 1D4T, 1D4W, 1KA6, 1KA7, 1M27
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00017	SH2	6 → 87	SH2 domain	Domain

• Sequence:

  MDAVAVYHGKISRETGEKLLLATGLDGSYLLRDSESVPGVYCLCVLYHGYIYTYRVSQTE
  TGSWSAETAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIRED
  PDVCLKAP

• Sequence length: 128

Pathways

KEGG:

Natural killer cell mediated cytotoxicity

Reactome:

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
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
Fulminant hepatitis	Fulminant hepatitis	rs1590835834
Lymphoma	Lymphoma	rs11540652, rs1592119138, rs1592123162, rs1599367044
Lymphoproliferative disorder	Lymphoproliferative Disorders	rs121908191, rs398122933, rs397514667, rs397514260, rs397514261, rs748418658, rs781593353	10229804
Lymphoproliferative syndrome, x-linked	X-linked lymphoproliferative disease due to SH2D1A deficiency, X-Linked Lymphoproliferative Disorder	rs111033623, rs111033628, rs111033624, rs1603238847, rs111033625, rs111033626, rs1603236465, rs111033629, rs111033630, rs1556404534, rs104894764, rs387907301, rs587777612, rs1556406033, rs1556404673, rs1556404697, rs1556404455, rs1556408009, rs1556404575, rs1556404684, rs1556619319, rs1556620706, rs1556620697, rs111978474, rs2053350325, rs1569477871, rs1569527111, rs1602546782, rs1602544507, rs1602562990, rs2053346219, rs2053348573	12458214, 15908972, 15661030, 27209435, 11049992, 15841490, 24985396, 15359110, 14583885, 11414741, 9811875, 22493517, 9774102, 12224001, 11034354, 11159547, 10229804, 14674764, 11493483, 11823424, 28196537, 9771704, 16720617, 10934222, 21707584, 10598819, 10694488, 11477068
Pancytopenia	Pancytopenia	rs869312883, rs770551610, rs1131690788, rs530073586, rs374333820

Unknown
Disease name	Disease term	dbSNP ID	References
Encephalitis	Encephalitis
Hepatic encephalopathy	Hepatic Encephalopathy
Immunologic deficiency syndromes	Immunologic Deficiency Syndromes
Leukopenia	Leukopenia
Lymphocytosis	Lymphocytosis
Respiratory failure	Respiratory Failure