CBS (cystathionine beta-synthase)

Gene

• Entrez ID: 875
• Gene name: Cystathionine beta-synthase
• Gene symbol: CBS
• Synonyms (NCBI Gene): CBSL, HIP4
• Chromosome: 21
• Chromosome location: 21q22.3
• Summary: The protein encoded by this gene acts as a homotetramer to catalyze the conversion of homocysteine to cystathionine, the first step in the transsulfuration pathway. The encoded protein is allosterically activated by adenosyl-methionine and uses pyridoxal

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT049293	hsa-miR-92a-3p	CLASH	23622248
MIRT049293	hsa-miR-92a-3p	CLASH	23622248
MIRT045521	hsa-miR-149-5p	CLASH	23622248
MIRT043169	hsa-miR-324-5p	CLASH	23622248
MIRT041577	hsa-miR-193b-3p	CLASH	23622248
MIRT040018	hsa-miR-615-3p	CLASH	23622248
MIRT039571	hsa-miR-652-3p	CLASH	23622248
MIRT038567	hsa-miR-106b-3p	CLASH	23622248
MIRT683818	hsa-miR-6732-3p	HITS-CLIP	23313552
MIRT683817	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT683816	hsa-miR-4421	HITS-CLIP	23313552
MIRT683815	hsa-miR-5699-3p	HITS-CLIP	23313552
MIRT683814	hsa-miR-3190-5p	HITS-CLIP	23313552
MIRT683813	hsa-miR-3926	HITS-CLIP	23313552
MIRT683812	hsa-miR-548s	HITS-CLIP	23313552
MIRT644216	hsa-miR-16-2-3p	HITS-CLIP	23824327
MIRT644215	hsa-miR-195-3p	HITS-CLIP	23824327
MIRT644214	hsa-miR-323b-3p	HITS-CLIP	23824327
MIRT644213	hsa-miR-3127-3p	HITS-CLIP	23824327
MIRT644212	hsa-miR-6756-3p	HITS-CLIP	23824327
MIRT644211	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT644209	hsa-miR-4713-5p	HITS-CLIP	23824327
MIRT644210	hsa-miR-6867-3p	HITS-CLIP	23824327
MIRT644208	hsa-miR-3672	HITS-CLIP	23824327
MIRT644207	hsa-miR-6864-3p	HITS-CLIP	23824327
MIRT644206	hsa-miR-629-3p	HITS-CLIP	23824327
MIRT644205	hsa-miR-8055	HITS-CLIP	23824327
MIRT644204	hsa-miR-129-5p	HITS-CLIP	23824327
MIRT631313	hsa-miR-6736-3p	HITS-CLIP	23824327
MIRT631312	hsa-miR-4267	HITS-CLIP	23824327
MIRT631311	hsa-miR-939-3p	HITS-CLIP	23824327
MIRT631310	hsa-miR-6852-5p	HITS-CLIP	23824327
MIRT631309	hsa-miR-6742-3p	HITS-CLIP	23824327
MIRT631308	hsa-miR-4667-5p	HITS-CLIP	23824327
MIRT631307	hsa-miR-4700-5p	HITS-CLIP	23824327
MIRT631306	hsa-miR-8089	HITS-CLIP	23824327
MIRT631305	hsa-miR-214-5p	HITS-CLIP	23824327
MIRT631304	hsa-miR-6811-3p	HITS-CLIP	23824327
MIRT631303	hsa-miR-3175	HITS-CLIP	23824327
MIRT631302	hsa-miR-1343-5p	HITS-CLIP	23824327
MIRT631301	hsa-miR-939-5p	HITS-CLIP	23824327
MIRT568996	hsa-miR-6825-5p	HITS-CLIP	23824327
MIRT631300	hsa-miR-1271-3p	HITS-CLIP	23824327
MIRT631299	hsa-miR-550a-3-5p	HITS-CLIP	23824327
MIRT631298	hsa-miR-550a-5p	HITS-CLIP	23824327
MIRT631297	hsa-miR-7977	HITS-CLIP	23824327
MIRT631296	hsa-miR-1343-3p	HITS-CLIP	23824327
MIRT631295	hsa-miR-6783-3p	HITS-CLIP	23824327
MIRT631294	hsa-miR-6514-3p	HITS-CLIP	23824327
MIRT631293	hsa-miR-3150a-3p	HITS-CLIP	23824327
MIRT631292	hsa-miR-6763-5p	HITS-CLIP	23824327
MIRT503874	hsa-miR-665	HITS-CLIP	23824327
MIRT487235	hsa-miR-483-5p	PAR-CLIP	20371350
MIRT568998	hsa-miR-4755-3p	PAR-CLIP	20371350
MIRT487232	hsa-miR-7-5p	PAR-CLIP	20371350
MIRT487231	hsa-miR-766-5p	PAR-CLIP	20371350
MIRT487230	hsa-miR-765	PAR-CLIP	20371350
MIRT568997	hsa-miR-7106-5p	PAR-CLIP	20371350
MIRT487229	hsa-miR-149-3p	PAR-CLIP	20371350
MIRT487228	hsa-miR-4728-5p	PAR-CLIP	20371350
MIRT487227	hsa-miR-6785-5p	PAR-CLIP	20371350
MIRT487225	hsa-miR-6883-5p	PAR-CLIP	20371350
MIRT568996	hsa-miR-6825-5p	PAR-CLIP	20371350
MIRT568995	hsa-miR-1202	PAR-CLIP	20371350
MIRT568994	hsa-miR-3972	PAR-CLIP	20371350
MIRT568993	hsa-miR-5006-5p	PAR-CLIP	20371350
MIRT503878	hsa-miR-4453	PAR-CLIP	23446348
MIRT503877	hsa-miR-4538	PAR-CLIP	23446348
MIRT503875	hsa-miR-4768-3p	PAR-CLIP	23446348
MIRT503876	hsa-miR-4459	PAR-CLIP	23446348
MIRT503874	hsa-miR-665	PAR-CLIP	23446348
MIRT503873	hsa-miR-6840-3p	PAR-CLIP	23446348
MIRT503872	hsa-miR-7854-3p	PAR-CLIP	23446348
MIRT503871	hsa-miR-4722-5p	PAR-CLIP	23446348
MIRT503870	hsa-miR-3689d	PAR-CLIP	23446348
MIRT503869	hsa-miR-6851-5p	PAR-CLIP	23446348
MIRT503868	hsa-miR-1273e	PAR-CLIP	23446348
MIRT487236	hsa-miR-580-5p	PAR-CLIP	23592263
MIRT487235	hsa-miR-483-5p	PAR-CLIP	23592263
MIRT487233	hsa-miR-6783-5p	PAR-CLIP	23592263
MIRT487234	hsa-miR-5093	PAR-CLIP	23592263
MIRT487232	hsa-miR-7-5p	PAR-CLIP	23592263
MIRT487231	hsa-miR-766-5p	PAR-CLIP	23592263
MIRT487230	hsa-miR-765	PAR-CLIP	23592263
MIRT487229	hsa-miR-149-3p	PAR-CLIP	23592263
MIRT487228	hsa-miR-4728-5p	PAR-CLIP	23592263
MIRT487227	hsa-miR-6785-5p	PAR-CLIP	23592263
MIRT487225	hsa-miR-6883-5p	PAR-CLIP	23592263
MIRT503868	hsa-miR-1273e	PAR-CLIP	26701625
MIRT503870	hsa-miR-3689d	PAR-CLIP	26701625
MIRT503876	hsa-miR-4459	PAR-CLIP	26701625
MIRT503874	hsa-miR-665	PAR-CLIP	26701625
MIRT503873	hsa-miR-6840-3p	PAR-CLIP	26701625
MIRT683817	hsa-miR-6849-3p	PAR-CLIP	26701625
MIRT503869	hsa-miR-6851-5p	PAR-CLIP	26701625
MIRT503868	hsa-miR-1273e	PAR-CLIP	27292025
MIRT503873	hsa-miR-6840-3p	PAR-CLIP	27292025
MIRT732800	hsa-miR-4317	Luciferase reporter assay, qRT-PCR, Western blotting	33318876
MIRT733679	hsa-miR-376a-3p	Luciferase reporter assay, qRT-PCR, Western blotting	32532171
MIRT683818	hsa-miR-6732-3p	HITS-CLIP	23313552
MIRT683817	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT683816	hsa-miR-4421	HITS-CLIP	23313552
MIRT683815	hsa-miR-5699-3p	HITS-CLIP	23313552
MIRT683814	hsa-miR-3190-5p	HITS-CLIP	23313552
MIRT683813	hsa-miR-3926	HITS-CLIP	23313552
MIRT683812	hsa-miR-548s	HITS-CLIP	23313552
MIRT644216	hsa-miR-16-2-3p	HITS-CLIP	23824327
MIRT644215	hsa-miR-195-3p	HITS-CLIP	23824327
MIRT644214	hsa-miR-323b-3p	HITS-CLIP	23824327
MIRT644213	hsa-miR-3127-3p	HITS-CLIP	23824327
MIRT644212	hsa-miR-6756-3p	HITS-CLIP	23824327
MIRT644211	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT644209	hsa-miR-4713-5p	HITS-CLIP	23824327
MIRT644210	hsa-miR-6867-3p	HITS-CLIP	23824327
MIRT644208	hsa-miR-3672	HITS-CLIP	23824327
MIRT644207	hsa-miR-6864-3p	HITS-CLIP	23824327
MIRT644206	hsa-miR-629-3p	HITS-CLIP	23824327
MIRT644205	hsa-miR-8055	HITS-CLIP	23824327
MIRT644204	hsa-miR-129-5p	HITS-CLIP	23824327
MIRT631313	hsa-miR-6736-3p	HITS-CLIP	23824327
MIRT631312	hsa-miR-4267	HITS-CLIP	23824327
MIRT631311	hsa-miR-939-3p	HITS-CLIP	23824327
MIRT631310	hsa-miR-6852-5p	HITS-CLIP	23824327
MIRT631309	hsa-miR-6742-3p	HITS-CLIP	23824327
MIRT631308	hsa-miR-4667-5p	HITS-CLIP	23824327
MIRT631307	hsa-miR-4700-5p	HITS-CLIP	23824327
MIRT631306	hsa-miR-8089	HITS-CLIP	23824327
MIRT631305	hsa-miR-214-5p	HITS-CLIP	23824327
MIRT631304	hsa-miR-6811-3p	HITS-CLIP	23824327
MIRT631303	hsa-miR-3175	HITS-CLIP	23824327
MIRT631302	hsa-miR-1343-5p	HITS-CLIP	23824327
MIRT631301	hsa-miR-939-5p	HITS-CLIP	23824327
MIRT568996	hsa-miR-6825-5p	HITS-CLIP	23824327
MIRT631300	hsa-miR-1271-3p	HITS-CLIP	23824327
MIRT631299	hsa-miR-550a-3-5p	HITS-CLIP	23824327
MIRT631298	hsa-miR-550a-5p	HITS-CLIP	23824327
MIRT631297	hsa-miR-7977	HITS-CLIP	23824327
MIRT631296	hsa-miR-1343-3p	HITS-CLIP	23824327
MIRT631295	hsa-miR-6783-3p	HITS-CLIP	23824327
MIRT631294	hsa-miR-6514-3p	HITS-CLIP	23824327
MIRT631293	hsa-miR-3150a-3p	HITS-CLIP	23824327
MIRT631292	hsa-miR-6763-5p	HITS-CLIP	23824327
MIRT503874	hsa-miR-665	HITS-CLIP	23824327
MIRT487235	hsa-miR-483-5p	PAR-CLIP	20371350
MIRT568998	hsa-miR-4755-3p	PAR-CLIP	20371350
MIRT487232	hsa-miR-7-5p	PAR-CLIP	20371350
MIRT487231	hsa-miR-766-5p	PAR-CLIP	20371350
MIRT487230	hsa-miR-765	PAR-CLIP	20371350
MIRT568997	hsa-miR-7106-5p	PAR-CLIP	20371350
MIRT487229	hsa-miR-149-3p	PAR-CLIP	20371350
MIRT487228	hsa-miR-4728-5p	PAR-CLIP	20371350
MIRT487227	hsa-miR-6785-5p	PAR-CLIP	20371350
MIRT487225	hsa-miR-6883-5p	PAR-CLIP	20371350
MIRT568996	hsa-miR-6825-5p	PAR-CLIP	20371350
MIRT568995	hsa-miR-1202	PAR-CLIP	20371350
MIRT568994	hsa-miR-3972	PAR-CLIP	20371350
MIRT568993	hsa-miR-5006-5p	PAR-CLIP	20371350
MIRT503878	hsa-miR-4453	PAR-CLIP	23446348
MIRT503877	hsa-miR-4538	PAR-CLIP	23446348
MIRT503875	hsa-miR-4768-3p	PAR-CLIP	23446348
MIRT503876	hsa-miR-4459	PAR-CLIP	23446348
MIRT503874	hsa-miR-665	PAR-CLIP	23446348
MIRT503873	hsa-miR-6840-3p	PAR-CLIP	23446348
MIRT503872	hsa-miR-7854-3p	PAR-CLIP	23446348
MIRT503871	hsa-miR-4722-5p	PAR-CLIP	23446348
MIRT503870	hsa-miR-3689d	PAR-CLIP	23446348
MIRT503869	hsa-miR-6851-5p	PAR-CLIP	23446348
MIRT503868	hsa-miR-1273e	PAR-CLIP	23446348
MIRT487236	hsa-miR-580-5p	PAR-CLIP	23592263
MIRT487235	hsa-miR-483-5p	PAR-CLIP	23592263
MIRT487233	hsa-miR-6783-5p	PAR-CLIP	23592263
MIRT487234	hsa-miR-5093	PAR-CLIP	23592263
MIRT487232	hsa-miR-7-5p	PAR-CLIP	23592263
MIRT487231	hsa-miR-766-5p	PAR-CLIP	23592263
MIRT487230	hsa-miR-765	PAR-CLIP	23592263
MIRT487229	hsa-miR-149-3p	PAR-CLIP	23592263
MIRT487228	hsa-miR-4728-5p	PAR-CLIP	23592263
MIRT487227	hsa-miR-6785-5p	PAR-CLIP	23592263
MIRT487225	hsa-miR-6883-5p	PAR-CLIP	23592263
MIRT865793	hsa-miR-1206	CLIP-seq
MIRT865794	hsa-miR-1297	CLIP-seq
MIRT865795	hsa-miR-1299	CLIP-seq
MIRT865796	hsa-miR-154	CLIP-seq
MIRT865797	hsa-miR-198	CLIP-seq
MIRT865798	hsa-miR-203	CLIP-seq
MIRT865799	hsa-miR-219-5p	CLIP-seq
MIRT865800	hsa-miR-26a	CLIP-seq
MIRT865801	hsa-miR-26b	CLIP-seq
MIRT865802	hsa-miR-4257	CLIP-seq
MIRT865803	hsa-miR-4275	CLIP-seq
MIRT865804	hsa-miR-4445	CLIP-seq
MIRT865805	hsa-miR-4452	CLIP-seq
MIRT865806	hsa-miR-4465	CLIP-seq
MIRT865807	hsa-miR-4729	CLIP-seq
MIRT865808	hsa-miR-4731-3p	CLIP-seq
MIRT865809	hsa-miR-4764-5p	CLIP-seq
MIRT865810	hsa-miR-4773	CLIP-seq
MIRT865811	hsa-miR-4782-3p	CLIP-seq
MIRT865812	hsa-miR-4782-5p	CLIP-seq
MIRT865813	hsa-miR-4793-5p	CLIP-seq
MIRT865814	hsa-miR-4801	CLIP-seq
MIRT865815	hsa-miR-498	CLIP-seq
MIRT865816	hsa-miR-508-3p	CLIP-seq
MIRT865817	hsa-miR-516b	CLIP-seq
MIRT865818	hsa-miR-542-3p	CLIP-seq
MIRT865819	hsa-miR-616	CLIP-seq
MIRT865794	hsa-miR-1297	CLIP-seq
MIRT865796	hsa-miR-154	CLIP-seq
MIRT865799	hsa-miR-219-5p	CLIP-seq
MIRT865800	hsa-miR-26a	CLIP-seq
MIRT865801	hsa-miR-26b	CLIP-seq
MIRT1956761	hsa-miR-3977	CLIP-seq
MIRT865804	hsa-miR-4445	CLIP-seq
MIRT865806	hsa-miR-4465	CLIP-seq
MIRT865807	hsa-miR-4729	CLIP-seq
MIRT865811	hsa-miR-4782-3p	CLIP-seq
MIRT865815	hsa-miR-498	CLIP-seq
MIRT865816	hsa-miR-508-3p	CLIP-seq
MIRT1956762	hsa-miR-7	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
NFYA	Activation	12427542
SP1	Unknown	11415440;14670973;20392694
SP3	Unknown	11415440

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001958	Process	Endochondral ossification	IEA
GO:0001974	Process	Blood vessel remodeling	IEA
GO:0003824	Function	Catalytic activity	IEA
GO:0004122	Function	Cystathionine beta-synthase activity	IBA
GO:0004122	Function	Cystathionine beta-synthase activity	IDA	7929220, 18776696, 19010420, 22985361, 23981774, 24416422
GO:0004122	Function	Cystathionine beta-synthase activity	IEA
GO:0005515	Function	Protein binding	IPI	16189514, 17087506, 21653829, 25416956, 31515488, 32296183, 32814053
GO:0005634	Component	Nucleus	IDA	17087506
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	23981774
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	HDA	16780588
GO:0005829	Component	Cytosol	TAS
GO:0006534	Process	Cysteine metabolic process	IEA
GO:0006535	Process	Cysteine biosynthetic process from serine	IBA
GO:0006535	Process	Cysteine biosynthetic process from serine	IEA
GO:0006563	Process	L-serine metabolic process	IDA	19010420
GO:0006565	Process	L-serine catabolic process	IDA	18776696
GO:0006801	Process	Superoxide metabolic process	IEA
GO:0008652	Process	Amino acid biosynthetic process	IEA
GO:0009069	Process	Serine family amino acid metabolic process	IEA
GO:0010749	Process	Regulation of nitric oxide mediated signal transduction	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0019343	Process	Cysteine biosynthetic process via cystathionine	IEA
GO:0019344	Process	Cysteine biosynthetic process	IDA	24416422
GO:0019344	Process	Cysteine biosynthetic process	IEA
GO:0019344	Process	Cysteine biosynthetic process	IEA
GO:0019346	Process	Transsulfuration	IEA
GO:0019448	Process	L-cysteine catabolic process	IDA	15520012
GO:0019825	Function	Oxygen binding	IDA	24515102
GO:0019899	Function	Enzyme binding	IPI	17087506
GO:0020037	Function	Heme binding	EXP	29410458
GO:0020037	Function	Heme binding	IDA	7929220, 24515102
GO:0020037	Function	Heme binding	IMP	18776696
GO:0021587	Process	Cerebellum morphogenesis	IEA
GO:0030170	Function	Pyridoxal phosphate binding	IDA	7929220, 18776696
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	17087506
GO:0031667	Process	Response to nutrient levels	IEA
GO:0042262	Process	DNA protection	IMP	24534463
GO:0042802	Function	Identical protein binding	IPI	16189514, 19447967, 21900206, 25416956, 25502805, 31515488
GO:0042803	Function	Protein homodimerization activity	IDA	11483494
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043418	Process	Homocysteine catabolic process	IDA	18776696, 24416422
GO:0044272	Process	Sulfur compound biosynthetic process	IEA
GO:0046328	Process	Regulation of JNK cascade	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0050421	Function	Nitrite reductase (NO-forming) activity	IDA	24416422
GO:0050667	Process	Homocysteine metabolic process	IDA	19010420, 20031578, 23981774
GO:0050667	Process	Homocysteine metabolic process	IEA
GO:0050667	Process	Homocysteine metabolic process	IEA
GO:0051593	Process	Response to folic acid	IEA
GO:0060135	Process	Maternal process involved in female pregnancy	IEA
GO:0060351	Process	Cartilage development involved in endochondral bone morphogenesis	IEA
GO:0070025	Function	Carbon monoxide binding	IDA	24515102
GO:0070026	Function	Nitric oxide binding	IDA	24416422, 24515102
GO:0070814	Process	Hydrogen sulfide biosynthetic process	IDA	15520012, 24416422
GO:0070814	Process	Hydrogen sulfide biosynthetic process	IEA
GO:0070814	Process	Hydrogen sulfide biosynthetic process	ISS
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0072341	Function	Modified amino acid binding	IDA	20031578
GO:0097746	Process	Blood vessel diameter maintenance	IEA
GO:1904047	Function	S-adenosyl-L-methionine binding	IDA	22985361

Other IDs

• MIM: 613381
• HGNC: 1550
• e!Ensembl: ENSG00000160200

Interactions View interactions

Pathways

KEGG:

Glycine, serine and threonine metabolism
Cysteine and methionine metabolism
One carbon pool by folate
Metabolic pathways
Biosynthesis of amino acids

Reactome:

Cysteine formation from homocysteine

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of metabolism/homeostasis	Likely pathogenic	rs2146394968	RCV001814578	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CBS-related disorder	Pathogenic; Likely pathogenic	rs121964962, rs121964964, rs121964966, rs28934891, rs375846341, rs121964973, rs786204757, rs372010465, rs778220779, rs1354271840, rs748695461, rs1555875325, rs762065361, rs751464024, rs373782713, rs398123151	RCV003914786 RCV003952330 RCV003415595 RCV004754226 RCV003944786 RCV003914787 RCV004754328 RCV003895256 RCV004754347 RCV003404293 RCV004754418 RCV003403565 RCV004754561 RCV003424337 RCV003918663 RCV003905038	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Classic homocystinuria	Likely pathogenic; Pathogenic	rs760417941, rs760912339, rs121964971, rs2146413970, rs2146428203, rs2146340713, rs1982513394, rs2146387904, rs2146414477, rs121964962, rs121964963, rs121964964, rs5742905, rs121964966, rs121964968, rs121964969, rs28934891, rs375846341, rs121964972, rs121964973, rs2517436753, rs2517399568, rs2517445243, rs2517412566, rs2517403114, rs2517483521, rs2517445086, rs2517470142, rs2517447331, rs786204466, rs786204679, rs763036586, rs771298943, rs758236584, rs775351239, rs764160782, rs770095972, rs760214620, rs786204757, rs775432669, rs794727083, rs781444670, rs149119723, rs2517442346, rs863223433, rs769080151, rs372010465, rs777919630, rs863223432, rs773734233, rs775992753, rs778220779, rs863223435, rs199948079, rs148865119, rs2517400216, rs779250698, rs1157774154, rs1354271840, rs1411597530, rs866630296, rs2517442518, rs1178687976, rs2517424159, rs775937459, rs948402447, rs2517394724, rs751464024, rs2517395819, rs2517399972, rs2517454033, rs2517442155, rs1294996414, rs2517445160, rs1449634173, rs1298089659, rs1982504069, rs2517411603, rs2517425105, rs2517413127, rs2517436554, rs2517424268, rs886057099, rs2517470463, rs2517448132, rs2517425362, rs886057100, rs1555874263, rs562885611, rs2517400347, rs2146362992, rs2517452797, rs2517436177, rs2517395485, rs1057516895, rs1057516645, rs781567152, rs1057517373, rs746575551, rs766453711, rs1057517435, rs763835246, rs767036273, rs755952006, rs1057517083, rs1057516256, rs1057516552, rs748695461, rs757920190, rs528689432, rs757428597, rs1361324844, rs1347651454, rs1555871188, rs143124288, rs1555872787, rs1555873925, rs1555874874, rs760609383, rs141502207, rs1555875325, rs755625628, rs1555876784, rs1555869934, rs1555869958, rs1555869979, rs1434118781, rs1555874121, rs763290176, rs1555874803, rs1555875292, rs1555871095, rs865990681, rs1555876755, rs1568932440, rs1234354755, rs762065361, rs1170128038, rs1601339216, rs1304669003, rs1981524462, rs376916741, rs373782713, rs1464223176, rs370167302, rs1438933819, rs1981682654, rs1982493665, rs758703098, rs1982601982, rs398123151	RCV001361230 RCV004570927 RCV001386107 RCV003462980 RCV003463025 RCV001507009 RCV001787317 RCV003464291 RCV003464378 RCV000173641 RCV000625555 RCV000490533 RCV000173640 RCV000169074 RCV000675072 RCV000469164 RCV000174656 RCV000174658 RCV000169466 RCV000576767 RCV004572125 RCV002306594 RCV002306682 RCV002309720 RCV002308210 RCV002306876 RCV002307175 RCV002307179 RCV002310319 RCV000169113 RCV000169487 RCV000169171 RCV000169132 RCV000169294 RCV000169175 RCV000169271 RCV000169322 RCV000169116 RCV000169617 RCV003234597 RCV000174443 RCV000178709 RCV000180461 RCV000190373 RCV003464608 RCV001275690 RCV000763061 RCV000410135 RCV003462305 RCV000363392 RCV003462304 RCV000475484 RCV000535881 RCV001063052 RCV000409663 RCV000410155 RCV003142718 RCV000279971 RCV003234731 RCV004572969 RCV003460335 RCV003460336 RCV003460337 RCV003460338 RCV003460339 RCV003460340 RCV003460341 RCV003460342 RCV003460343 RCV003460344 RCV003460345 RCV003460346 RCV003460347 RCV003460348 RCV003460349 RCV003460350 RCV003460351 RCV003460352 RCV003460353 RCV003460354 RCV003460355 RCV003460356 RCV003448861 RCV003989272 RCV004018179 RCV004018180 RCV004018181 RCV004018182 RCV004018213 RCV004018214 RCV000667483 RCV004575494 RCV004575495 RCV004575496 RCV004575497 RCV004575498 RCV004575499 RCV004575500 RCV000409904 RCV000412412 RCV000409189 RCV000410016 RCV000409556 RCV000411137 RCV000410740 RCV000409103 RCV000412334 RCV000412346 RCV000411624 RCV000411736 RCV000411421 RCV000409345 RCV000409242 RCV000409151 RCV003464007 RCV000673238 RCV000544919 RCV000666270 RCV003459454 RCV000984247 RCV003459543 RCV000665384 RCV000668276 RCV000670102 RCV000673555 RCV000671969 RCV000671575 RCV000673689 RCV000674577 RCV000669819 RCV000674825 RCV000666158 RCV000672976 RCV000669704 RCV000670219 RCV000672813 RCV000673023 RCV000669206 RCV000668133 RCV000669346 RCV000670285 RCV000670125 RCV000692522 RCV000704014 RCV001220158 RCV001389140 RCV002510583 RCV003485647 RCV001004615 RCV004570272 RCV005630865 RCV001070719 RCV003462597 RCV001833732 RCV005606774 RCV003117854 RCV001257457 RCV001264020 RCV001264021 RCV001264022 RCV001264023 RCV001264024 RCV000169310	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Connective tissue disorder	Pathogenic	rs5742905	RCV002276525	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial thoracic aortic aneurysm and aortic dissection	Likely pathogenic; Pathogenic	rs760417941, rs121964962, rs121964964, rs5742905, rs121964969, rs28934891, rs375846341, rs121964972, rs121964973, rs771298943, rs764160782, rs770095972, rs781444670, rs149119723, rs372010465, rs777919630, rs778220779, rs148865119, rs766453711, rs755952006, rs528689432, rs1347651454, rs141502207, rs373782713	RCV002420789 RCV002313701 RCV002453244 RCV002310621 RCV002313702 RCV002381232 RCV002354142 RCV004018522 RCV004018523 RCV002390401 RCV004821988 RCV002453568 RCV004821993 RCV004821994 RCV002433873 RCV005791831 RCV006276137 RCV002310761 RCV005791849 RCV002328897 RCV005306050 RCV002315881 RCV004026125 RCV002339345	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hepatocellular carcinoma	Pathogenic	rs375846341	RCV005887117	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Homocystinuria	Likely pathogenic; Pathogenic	rs760912339, rs141502207, rs2146362992, rs1376851289, rs121964962, rs121964963, rs121964964, rs5742905, rs121964966, rs121964968, rs121964969, rs28934891, rs375846341, rs121964972, rs121964973, rs786204466, rs763036586, rs771298943, rs758236584, rs775351239, rs764160782, rs770095972, rs760214620, rs786204757, rs781444670, rs149119723, rs769080151, rs372010465, rs777919630, rs773734233, rs775992753, rs778220779, rs199948079, rs2517425362, rs775937459, rs1982504069, rs769438280, rs2517429781, rs886057100, rs760417941, rs781567152, rs1057517373, rs763835246, rs755952006, rs748695461, rs757920190, rs757428597, rs1361324844, rs1347651454, rs143124288, rs1555874874, rs755625628, rs763290176, rs1555874803, rs762065361, rs751464024, rs1170128038, rs1304669003, rs373782713, rs1464223176, rs370167302, rs398123151	RCV005237766 RCV001553570 RCV001825051 RCV005238137 RCV000366433 RCV001250193 RCV000590659 RCV000781197 RCV001251284 RCV002468955 RCV001192721 RCV000781196 RCV000590542 RCV002271361 RCV000589097 RCV001175467 RCV004689648 RCV000780082 RCV000780084 RCV003226231 RCV000780083 RCV001192720 RCV001844063 RCV001251397 RCV001804908 RCV001251422 RCV003987440 RCV003401061 RCV001778782 RCV000586183 RCV001192722 RCV000588375 RCV002282028 RCV003155600 RCV005062970 RCV006262822 RCV005240833 RCV003995083 RCV001175468 RCV001584104 RCV000780081 RCV001251295 RCV001527049 RCV001193389 RCV001193390 RCV003155205 RCV001260387 RCV000588547 RCV000587735 RCV003226347 RCV005407871 RCV002282314 RCV003987658 RCV003226363 RCV003330883 RCV000781199 RCV000780080 RCV005901988 RCV003994188 RCV001264436 RCV001175076 RCV001193391 RCV004768939 RCV001280568	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Homocystinuria, pyridoxine-nonresponsive	Pathogenic	rs121964962, rs121964972, rs121964973	RCV000000137 RCV000000154 RCV000000155	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Homocystinuria, pyridoxine-responsive	Likely pathogenic; Pathogenic	rs121964963, rs121964964, rs5742905, rs121964966, rs121964967, rs121964968, rs121964969, rs28934891, rs375846341	RCV000000139 RCV000000140 RCV000000141 RCV000000144 RCV000000145 RCV000000146 RCV000000147 RCV000000148 RCV000000151	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperhomocysteinemia	Likely pathogenic; Pathogenic	rs758236584	RCV000790997	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	Likely pathogenic; Pathogenic	rs760417941, rs777956934, rs760912339, rs2146395543, rs121964971, rs2146413970, rs2146428203, rs1208139876, rs2146387904, rs1376851289, rs2146414477, rs1207298097, rs2146427913, rs2146427112, rs2146427772, rs2146366969, rs774174074, rs2146387963, rs1166621523, rs2146393621, rs377708532, rs2146344203, rs2146427417, rs2146385603, rs2146381604, rs2146393861, rs111687029, rs121964962, rs121964963, rs121964964, rs5742905, rs121964966, rs121964967, rs121964968, rs121964969, rs28934891, rs375846341, rs1191141364, rs121964972, rs121964973, rs2517436753, rs1398459455, rs2517424483, rs1568929135, rs786204466, rs786204679, rs763036586, rs771298943, rs758236584, rs775351239, rs764160782, rs770095972, rs760214620, rs786204757, rs775432669, rs1463986810, rs794727083, rs2517429476, rs781444670, rs149119723, rs2517483238, rs2517452643, rs2517411603, rs1443213281, rs2517442346, rs2517453736, rs1308193541, rs2517483668, rs1180993602, rs769080151, rs372010465, rs777919630, rs863223432, rs863223430, rs773734233, rs762065361, rs775992753, rs778220779, rs863223435, rs199948079, rs148865119, rs2517382043, rs779250698, rs1354271840, rs2517442518, rs2517445160, rs1298089659, rs2517436400, rs2517469721, rs2517453201, rs2517436960, rs2517428448, rs1242898623, rs2517437166, rs769438280, rs2517413033, rs398123151, rs2517469815, rs2517447078, rs763890444, rs2517447876, rs2517483376, rs2517366385, rs2517469335, rs2517454427, rs2517365943, rs1323224189, rs764638041, rs1347662650, rs763835246, rs886057100, rs1057516895, rs781567152, rs1057517373, rs766453711, rs755952006, rs1057517083, rs1057516256, rs751464024, rs748695461, rs757920190, rs1064794540, rs1064793703, rs528689432, rs757428597, rs1361324844, rs1347651454, rs1555871188, rs143124288, rs760609383, rs755625628, rs1555876784, rs1555869958, rs1555869979, rs1434118781, rs1555874121, rs763290176, rs1555874803, rs1555875292, rs865990681, rs1568932835, rs1234354755, rs1170128038, rs1601339216, rs1981524462, rs376916741, rs373782713, rs1983442077, rs1464223176, rs1332950288, rs370167302, rs1983427704, rs1982618780	RCV003154014 RCV002242771 RCV002242773 RCV002242780 RCV002242843 RCV002242808 RCV002242852 RCV002004499 RCV001999818 RCV002024992 RCV002017343 RCV001973905 RCV002006214 RCV002023684 RCV002042352 RCV002044527 RCV001994637 RCV001994462 RCV002002996 RCV001953493 RCV002036189 RCV001885847 RCV001956301 RCV001931836 RCV001906527 RCV001949618 RCV001973630 RCV000000138 RCV002227955 RCV002227956 RCV000000142 RCV002227957 RCV003495103 RCV003597960 RCV002227958 RCV000000149 RCV002227960 RCV001981105 RCV002227961 RCV002227962 RCV003101691 RCV003064630 RCV003064631 RCV003064632 RCV002228605 RCV002228614 RCV002517626 RCV002228607 RCV002228778 RCV002228608 RCV002228777 RCV002228611 RCV002228606 RCV002228615 RCV003075119 RCV002619242 RCV002615667 RCV001852126 RCV002663971 RCV002228790 RCV002228800 RCV002730976 RCV002780358 RCV001857669 RCV002828990 RCV002828991 RCV002833705 RCV002834464 RCV002857576 RCV002885292 RCV002889834 RCV001853130 RCV002229026 RCV002228833 RCV003495115 RCV002517165 RCV002228832 RCV003496988 RCV002229025 RCV002229441 RCV002228834 RCV002229029 RCV002229028 RCV003044032 RCV002229737 RCV005061393 RCV003495344 RCV003779147 RCV003779148 RCV003598178 RCV003495499 RCV003495354 RCV003496394 RCV003497077 RCV003496954 RCV003494862 RCV003494762 RCV003494763 RCV003494764 RCV003494765 RCV003494889 RCV003494982 RCV003495869 RCV003495852 RCV003598181 RCV003598197 RCV003598372 RCV003598978 RCV003599549 RCV003599632 RCV003599745 RCV003597516 RCV003597619 RCV003597714 RCV003597752 RCV003598641 RCV003598642 RCV003598741 RCV003598735 RCV003850481 RCV003865809 RCV002231054 RCV001861382 RCV002230729 RCV001861384 RCV001861397 RCV002230728 RCV002230214 RCV002230731 RCV002230218 RCV002230213 RCV002230215 RCV002230730 RCV003495133 RCV003495134 RCV002230902 RCV002231627 RCV002231187 RCV002232086 RCV002232222 RCV002232223 RCV001867959 RCV002235503 RCV002233102 RCV003597996 RCV002531362 RCV003495172 RCV002232803 RCV005091950 RCV002233103 RCV002232806 RCV002232634 RCV001861765 RCV002232804 RCV002233699 RCV002233403 RCV002234174 RCV002234171 RCV002234919 RCV002235005 RCV002240613 RCV002240537 RCV002240636 RCV002240573 RCV002240520 RCV003495233 RCV002241267 RCV002241315 RCV002241256 RCV002241644 RCV002228199	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intellectual disability	Pathogenic	rs5742905	RCV001252178	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thoracic aortic aneurysm or dissection	Pathogenic	rs5742905	RCV004584135	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOVASCULAR DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiovascular phenotype	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CEREBRAL INFARCTION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC ISCHEMIC HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL CONTRACTURAL ARACHNODACTYLY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital myopathy	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONNECTIVE TISSUE DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERIOSCLEROSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CYSTATHIONINE BETA-SYNTHASE DEFICIENCY DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, NON-INSULIN-DEPENDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, TYPE 2	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MALNUTRITION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL ISCHEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURAL TUBE DEFECT, FOLATE-SENSITIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURAL TUBE DEFECTS X-LINKED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations