BCKDHA (branched chain keto acid dehydrogenase E1 subunit alpha)

Gene

• Entrez ID: 593
• Gene name: Branched chain keto acid dehydrogenase E1 subunit alpha
• Gene symbol: BCKDHA
• Synonyms (NCBI Gene): BCKDE1A, MSU, MSUD1, MSUD1A, OVD1A
• Chromosome: 19
• Chromosome location: 19q13.2
• Summary: The branched-chain alpha-keto acid (BCAA) dehydrogenase (BCKD) complex is an innter mitochondrial enzyme complex that catalyzes the second major step in the catabolism of the branched-chain amino acids leucine, isoleucine, and valine. The BCKD complex con

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137852870	T>A	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs137852871	G>A,C	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs137852872	T>G	Pathogenic	Coding sequence variant, missense variant
rs137852873	C>T	Conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs137852874	G>A	Pathogenic	Coding sequence variant, missense variant
rs137852875	C>G	Pathogenic	Coding sequence variant, missense variant
rs137852876	C>G	Pathogenic	Coding sequence variant, missense variant
rs146932786	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs147021347	C>G,T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs151227241	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs182923857	C>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs199599175	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs201168715	G>A,T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, stop gained
rs367823977	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs373336888	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs373390136	C>A,G,T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs373713279	C>A	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs374625613	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs375785084	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs376456598	C>A	Likely-pathogenic	Coding sequence variant, stop gained
rs398123486	G>A	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs398123489	C>-,CC,CCC	Pathogenic	Coding sequence variant, frameshift variant
rs398123490	G>A	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs398123491	C>A,T	Likely-benign, pathogenic	Stop gained, coding sequence variant, synonymous variant
rs398123492	AC>-	Pathogenic	Coding sequence variant, frameshift variant
rs398123493	C>A	Pathogenic	Stop gained, coding sequence variant
rs398123496	G>A	Pathogenic-likely-pathogenic, pathogenic	Splice donor variant
rs398123497	C>T	Conflicting-interpretations-of-pathogenicity, pathogenic	Intron variant
rs398123499	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs398123503	C>T	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs398123504	->T	Pathogenic	Coding sequence variant, frameshift variant
rs398123505	TCT>-	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Inframe deletion, coding sequence variant
rs398123508	G>C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs398123509	A>C	Pathogenic	Coding sequence variant, missense variant
rs398123510	GT>-	Pathogenic	Coding sequence variant, frameshift variant
rs398123512	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs398123513	C>T	Pathogenic	Stop gained, coding sequence variant
rs398123514	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant, synonymous variant
rs398123515	G>A	Pathogenic-likely-pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs753216964	G>C	Likely-pathogenic, pathogenic	Splice acceptor variant
rs753698250	C>A,T	Pathogenic	Synonymous variant, stop gained, coding sequence variant
rs760494152	A>G	Pathogenic	Splice acceptor variant, intron variant
rs762084007	C>-	Pathogenic-likely-pathogenic	Coding sequence variant, frameshift variant
rs762199542	C>T	Pathogenic	Coding sequence variant, stop gained
rs764247545	C>G,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs765543886	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs773048903	G>A	Pathogenic	Missense variant, coding sequence variant
rs794727847	AGGCCCCG>-	Pathogenic	Frameshift variant, coding sequence variant
rs796051938	TACG>-	Likely-pathogenic, pathogenic	Frameshift variant, coding sequence variant
rs863225262	A>T	Pathogenic-likely-pathogenic	Coding sequence variant, stop gained
rs869312124	G>C	Pathogenic	Missense variant, coding sequence variant
rs869312125	A>C	Pathogenic	Missense variant, coding sequence variant
rs1057519059	C>AA	Pathogenic	Coding sequence variant, frameshift variant
rs1330793674	CAGCACCA>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1555765593	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555766066	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1555766993	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555767028	G>T	Likely-pathogenic	Splice donor variant
rs1555767090	->A	Likely-pathogenic	Coding sequence variant, stop gained
rs1555767169	G>-	Likely-pathogenic	Coding sequence variant, splice donor variant
rs1555767285	A>G	Likely-pathogenic	Splice acceptor variant
rs1568503938	T>C	Pathogenic	Coding sequence variant, missense variant
rs1568506608	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1599962569	CCAAGGCTGG>-	Likely-pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT044243	hsa-miR-29c-3p	CLASH	23622248
MIRT041443	hsa-miR-193b-3p	CLASH	23622248
MIRT818021	hsa-miR-1185	CLIP-seq
MIRT818022	hsa-miR-1293	CLIP-seq
MIRT818023	hsa-miR-2392	CLIP-seq
MIRT818024	hsa-miR-3605-5p	CLIP-seq
MIRT818025	hsa-miR-3615	CLIP-seq
MIRT818026	hsa-miR-3679-5p	CLIP-seq
MIRT818027	hsa-miR-4483	CLIP-seq
MIRT1941782	hsa-miR-194	CLIP-seq
MIRT1941783	hsa-miR-3661	CLIP-seq
MIRT1941784	hsa-miR-3929	CLIP-seq
MIRT1941785	hsa-miR-4419b	CLIP-seq
MIRT1941786	hsa-miR-4438	CLIP-seq
MIRT1941787	hsa-miR-4478	CLIP-seq
MIRT1941788	hsa-miR-4659a-5p	CLIP-seq
MIRT1941789	hsa-miR-4659b-5p	CLIP-seq
MIRT1941790	hsa-miR-4722-3p	CLIP-seq
MIRT1941791	hsa-miR-4769-3p	CLIP-seq
MIRT1941792	hsa-miR-631	CLIP-seq
MIRT2180689	hsa-miR-3692	CLIP-seq
MIRT1941784	hsa-miR-3929	CLIP-seq
MIRT1941785	hsa-miR-4419b	CLIP-seq
MIRT1941786	hsa-miR-4438	CLIP-seq
MIRT1941787	hsa-miR-4478	CLIP-seq
MIRT2180690	hsa-miR-4656	CLIP-seq
MIRT2180691	hsa-miR-4709-3p	CLIP-seq
MIRT818021	hsa-miR-1185	CLIP-seq
MIRT818022	hsa-miR-1293	CLIP-seq
MIRT818023	hsa-miR-2392	CLIP-seq
MIRT818024	hsa-miR-3605-5p	CLIP-seq
MIRT818026	hsa-miR-3679-5p	CLIP-seq
MIRT818027	hsa-miR-4483	CLIP-seq
MIRT2484072	hsa-miR-1303	CLIP-seq
MIRT2484073	hsa-miR-1539	CLIP-seq
MIRT2484074	hsa-miR-1909	CLIP-seq
MIRT1941782	hsa-miR-194	CLIP-seq
MIRT2484075	hsa-miR-2110	CLIP-seq
MIRT2484076	hsa-miR-3127-3p	CLIP-seq
MIRT2484077	hsa-miR-3140-5p	CLIP-seq
MIRT2484078	hsa-miR-3151	CLIP-seq
MIRT2484079	hsa-miR-3160-3p	CLIP-seq
MIRT2484080	hsa-miR-3184	CLIP-seq
MIRT2484081	hsa-miR-331-3p	CLIP-seq
MIRT2484082	hsa-miR-3650	CLIP-seq
MIRT1941783	hsa-miR-3661	CLIP-seq
MIRT2180689	hsa-miR-3692	CLIP-seq
MIRT1941784	hsa-miR-3929	CLIP-seq
MIRT2484083	hsa-miR-423-5p	CLIP-seq
MIRT2484084	hsa-miR-4271	CLIP-seq
MIRT2484085	hsa-miR-4283	CLIP-seq
MIRT2484086	hsa-miR-4290	CLIP-seq
MIRT2484087	hsa-miR-4292	CLIP-seq
MIRT2484088	hsa-miR-4300	CLIP-seq
MIRT2484089	hsa-miR-4419a	CLIP-seq
MIRT1941785	hsa-miR-4419b	CLIP-seq
MIRT1941786	hsa-miR-4438	CLIP-seq
MIRT1941787	hsa-miR-4478	CLIP-seq
MIRT2484090	hsa-miR-4481	CLIP-seq
MIRT2484091	hsa-miR-4489	CLIP-seq
MIRT2484092	hsa-miR-4510	CLIP-seq
MIRT2484093	hsa-miR-4540	CLIP-seq
MIRT2484094	hsa-miR-455-5p	CLIP-seq
MIRT2484095	hsa-miR-4632	CLIP-seq
MIRT1941788	hsa-miR-4659a-5p	CLIP-seq
MIRT1941789	hsa-miR-4659b-5p	CLIP-seq
MIRT2484096	hsa-miR-4667-5p	CLIP-seq
MIRT2484097	hsa-miR-4700-5p	CLIP-seq
MIRT2180691	hsa-miR-4709-3p	CLIP-seq
MIRT1941790	hsa-miR-4722-3p	CLIP-seq
MIRT2484098	hsa-miR-4725-3p	CLIP-seq
MIRT2484099	hsa-miR-4745-5p	CLIP-seq
MIRT1941791	hsa-miR-4769-3p	CLIP-seq
MIRT2484100	hsa-miR-496	CLIP-seq
MIRT2484101	hsa-miR-554	CLIP-seq
MIRT2484102	hsa-miR-626	CLIP-seq
MIRT1941792	hsa-miR-631	CLIP-seq
MIRT2484103	hsa-miR-7	CLIP-seq
MIRT2484104	hsa-miR-765	CLIP-seq
MIRT2484105	hsa-miR-877	CLIP-seq
MIRT2484106	hsa-miR-885-3p	CLIP-seq
MIRT2484107	hsa-miR-920	CLIP-seq
MIRT2484072	hsa-miR-1303	CLIP-seq
MIRT2484073	hsa-miR-1539	CLIP-seq
MIRT2484074	hsa-miR-1909	CLIP-seq
MIRT1941782	hsa-miR-194	CLIP-seq
MIRT2484075	hsa-miR-2110	CLIP-seq
MIRT2484076	hsa-miR-3127-3p	CLIP-seq
MIRT2484077	hsa-miR-3140-5p	CLIP-seq
MIRT2484079	hsa-miR-3160-3p	CLIP-seq
MIRT2484080	hsa-miR-3184	CLIP-seq
MIRT2484081	hsa-miR-331-3p	CLIP-seq
MIRT2484082	hsa-miR-3650	CLIP-seq
MIRT1941783	hsa-miR-3661	CLIP-seq
MIRT2180689	hsa-miR-3692	CLIP-seq
MIRT1941784	hsa-miR-3929	CLIP-seq
MIRT2484083	hsa-miR-423-5p	CLIP-seq
MIRT2484084	hsa-miR-4271	CLIP-seq
MIRT2484086	hsa-miR-4290	CLIP-seq
MIRT2484087	hsa-miR-4292	CLIP-seq
MIRT2484088	hsa-miR-4300	CLIP-seq
MIRT2484089	hsa-miR-4419a	CLIP-seq
MIRT1941785	hsa-miR-4419b	CLIP-seq
MIRT1941786	hsa-miR-4438	CLIP-seq
MIRT1941787	hsa-miR-4478	CLIP-seq
MIRT2484090	hsa-miR-4481	CLIP-seq
MIRT2484092	hsa-miR-4510	CLIP-seq
MIRT2484093	hsa-miR-4540	CLIP-seq
MIRT2484094	hsa-miR-455-5p	CLIP-seq
MIRT2484095	hsa-miR-4632	CLIP-seq
MIRT1941788	hsa-miR-4659a-5p	CLIP-seq
MIRT1941789	hsa-miR-4659b-5p	CLIP-seq
MIRT2484096	hsa-miR-4667-5p	CLIP-seq
MIRT2484097	hsa-miR-4700-5p	CLIP-seq
MIRT2180691	hsa-miR-4709-3p	CLIP-seq
MIRT1941790	hsa-miR-4722-3p	CLIP-seq
MIRT2484098	hsa-miR-4725-3p	CLIP-seq
MIRT2484099	hsa-miR-4745-5p	CLIP-seq
MIRT1941791	hsa-miR-4769-3p	CLIP-seq
MIRT2484100	hsa-miR-496	CLIP-seq
MIRT2484101	hsa-miR-554	CLIP-seq
MIRT2484102	hsa-miR-626	CLIP-seq
MIRT1941792	hsa-miR-631	CLIP-seq
MIRT2484103	hsa-miR-7	CLIP-seq
MIRT2484104	hsa-miR-765	CLIP-seq
MIRT2484105	hsa-miR-877	CLIP-seq
MIRT2484106	hsa-miR-885-3p	CLIP-seq
MIRT2484107	hsa-miR-920	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003863	Function	Branched-chain 2-oxo acid dehydrogenase activity	IDA	9582350, 10745006
GO:0003863	Function	Branched-chain 2-oxo acid dehydrogenase activity	IDA	7883996
GO:0003863	Function	Branched-chain 2-oxo acid dehydrogenase activity	IEA
GO:0005515	Function	Protein binding	IPI	10745006, 12902323, 15166214, 15576032, 28514442, 33961781
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	TAS	11839747
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	ISS
GO:0005759	Component	Mitochondrial matrix	NAS	3593587
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0009083	Process	Branched-chain amino acid catabolic process	IBA
GO:0009083	Process	Branched-chain amino acid catabolic process	IDA	3593587, 7883996
GO:0009083	Process	Branched-chain amino acid catabolic process	IMP	9582350
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016624	Function	Oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor	IEA
GO:0016831	Function	Carboxy-lyase activity	TAS	11839747
GO:0046872	Function	Metal ion binding	IEA
GO:0120552	Process	Branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA	IDA	3593587
GO:0120552	Process	Branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA	IMP	10745006
GO:0160157	Component	Branched-chain alpha-ketoacid dehydrogenase complex	IBA
GO:0160157	Component	Branched-chain alpha-ketoacid dehydrogenase complex	IDA	7883996, 9582350, 10745006
GO:0160157	Component	Branched-chain alpha-ketoacid dehydrogenase complex	IPI	3593587

Other IDs

• MIM: 608348
• HGNC: 986
• e!Ensembl: ENSG00000248098

Protein

• UniProt ID: P12694
• Protein name: 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (EC 1.2.4.4) (Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain) (BCKDE1A) (BCKDH E1-alpha)
• Protein function: Together with BCKDHB forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the b
• PDB: 1DTW, 1OLS, 1OLU, 1OLX, 1U5B, 1V11, 1V16, 1V1M, 1V1R, 1WCI, 1X7W, 1X7X, 1X7Y, 1X7Z, 1X80, 2BEU, 2BEV, 2BEW, 2BFB, 2BFC, 2BFD, 2BFE, 2BFF, 2J9F
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00676	E1_dh	106 → 406	Dehydrogenase E1 component	Family

• Sequence:

  MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQFSSLDDKPQFPGASAE
  FIDKLEFIQPNVISGIPIYRVMDRQGQIINPSEDPHLPKEKVLKLYKSMTLLNTMDRILY
  ESQRQGRISFYMTNYGEEGTHVGSAAALDNTDLVFGQYREAGVLMYRDYPLELFMAQCYG
  NISDLGKGRQMPVHYGCKERHFVTISSPLATQIPQAVGAAYAAKRANANRVVICYFGEGA
  ASEGDAHAGFNFAATLECPIIFFCRNNGYAISTPTSEQYRGDGIAARGPGYGIMSIRVDG
  NDVFAVYNATKEARRRAVAENQPFLIEAMTYRIGHHSTSDDSSAYRSVDEVNYWDKQDHP
  ISRLRHYLLSQGWWDEEQEKAWRKQSRRKVMEAFEQAERKPKPNPNLLFSDVYQEMPAQL
  RKQQESLARHLQTYGEHYPLDHFDK

• Sequence length: 445

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
BCKDHA-related disorder	Likely pathogenic; Pathogenic	rs369448982	RCV003892844	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cervical cancer	Pathogenic	rs398123508	RCV005886256	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial cancer of breast	Likely pathogenic	rs756052603	RCV005934651	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Likely inborn error of metabolism	Pathogenic	rs398123489	RCV005865250	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Malignant tumor of esophagus	Likely pathogenic	rs558254502	RCV005930523	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Maple syrup urine disease	Likely pathogenic; Pathogenic	rs2039383036, rs2123253583, rs761996996, rs2098470870, rs398123489, rs1220443382, rs2122142979, rs1318419473, rs1298823471, rs2122146680, rs369448982, rs2122143379, rs2122122667, rs2123232744, rs137852870, rs2123254646, rs765045050, rs752700457, rs2122142757, rs774735002, rs1207966026, rs137852874, rs757457825, rs2122146208, rs1213596075, rs2122122610, rs137852871, rs137852872, rs137852875, rs1437382824, rs2513459631, rs2513454376, rs2513454434, rs2039375116, rs2513452327, rs2513460533, rs2513452367, rs2513459717, rs2513452174, rs755451300, rs558254502, rs2513443919, rs794727847, rs1200370519, rs796051938, rs869312125, rs773048903, rs869312124, rs863225262, rs754613642, rs2513443720, rs2513459729, rs2513443854, rs398123509, rs2513459641, rs753452195, rs753698250, rs2513443827, rs2513462341, rs2513454343, rs904711508, rs2513459912, rs2513454323, rs1322799946, rs2513452355, rs2513457503, rs2513462327, rs2513459825, rs2513452055, rs2039242108, rs755433978, rs2513457448, rs2513462216, rs963488715, rs749487379, rs2513460625, rs1555767028, rs796051937, rs2513462321, rs754303047, rs2513452452, rs2513461217, rs2513461198, rs756052603, rs2513454359, rs1771148109, rs2513460449, rs1176952770, rs376456598, rs1057519059, rs753216964, rs1555767285, rs188135164, rs760494152, rs762084007, rs1555765593, rs769688327, rs199599175, rs764247545, rs1555766993, rs765543886, rs1330793674, rs1555767169, rs374625613, rs942815730, rs755691417, rs1568499702, rs1568503938, rs1568506608, rs762199542, rs1599962569, rs2039372961, rs2039405116, rs2039407382, rs2039285328, rs1214763792, rs2039247540, rs2039389302, rs2039242789, rs1459441231, rs575806482, rs1303770209, rs2039381583, rs398123486, rs398123490, rs398123492, rs398123494, rs398123496, rs398123497, rs398123499, rs398123503, rs375785084, rs398123504, rs398123508, rs200137189, rs398123510, rs398123513, rs398123515	RCV002642394 RCV001378292 RCV001376744 RCV001378139 RCV001389698 RCV001380797 RCV001388645 RCV001387039 RCV001385732 RCV001580640 RCV001780680 RCV001785342 RCV001837053 RCV001839175 RCV001848605 RCV001950826 RCV002040176 RCV002008317 RCV001954865 RCV001919750 RCV001951278 RCV002043368 RCV002018388 RCV001984178 RCV002043878 RCV002249293 RCV000055825 RCV000179775 RCV001378888 RCV001064270 RCV002222336 RCV000984155 RCV002308594 RCV002306580 RCV002306807 RCV002309961 RCV002307977 RCV002308121 RCV002307216 RCV002310105 RCV002310213 RCV002310363 RCV003078024 RCV002579160 RCV003083151 RCV000179782 RCV002621450 RCV000408793 RCV000209796 RCV000209016 RCV000209700 RCV000202366 RCV002736209 RCV002819464 RCV002852413 RCV002857744 RCV002903690 RCV003019195 RCV003014725 RCV000209887 RCV003155795 RCV003388964 RCV003465149 RCV003465150 RCV003465152 RCV003465153 RCV003465154 RCV003465155 RCV003465156 RCV003465157 RCV003465159 RCV003465160 RCV003465161 RCV003465162 RCV003465164 RCV003465165 RCV003523882 RCV003524117 RCV003524329 RCV003522340 RCV003523581 RCV003524677 RCV003636141 RCV003636350 RCV003637012 RCV003637121 RCV003637296 RCV003637812 RCV003637895 RCV003636548 RCV003636808 RCV003838017 RCV000409408 RCV000415547 RCV000670031 RCV000668125 RCV000526694 RCV001379040 RCV000601066 RCV000625789 RCV000669276 RCV000674422 RCV000669536 RCV000674650 RCV000673741 RCV000672950 RCV000673876 RCV000672530 RCV000665755 RCV000674875 RCV000673920 RCV000694889 RCV000761534 RCV000761473 RCV000785061 RCV000792298 RCV001035319 RCV001197612 RCV001216538 RCV001209953 RCV001204854 RCV001235560 RCV001244572 RCV001264340 RCV001264341 RCV001263561 RCV001263562 RCV001263563 RCV000180182 RCV000175640 RCV000180522 RCV003460745 RCV001854397 RCV000175639 RCV000175638 RCV001854398 RCV000178794 RCV000179335 RCV002514395 RCV000179337 RCV000664897 RCV001283857 RCV002514396 RCV001854399 RCV000179779	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple syrup urine disease type 1A	Likely pathogenic; Pathogenic	rs2039383036, rs761996996, rs369448982, rs2123232769, rs2122143379, rs137852870, rs2122122610, rs137852871, rs137852874, rs137852875, rs398123489, rs2513443919, rs794727847, rs773048903, rs863225262, rs754613642, rs753698250, rs1322799946, rs2513460977, rs2039242108, rs755433978, rs2513457448, rs2513461198, rs1771148109, rs2467811607, rs1325848718, rs2513452038, rs2513452044, rs2513461024, rs376456598, rs753216964, rs1555767285, rs188135164, rs760494152, rs762084007, rs1555765593, rs769688327, rs199599175, rs764247545, rs1555766993, rs1555767090, rs765543886, rs1555764014, rs1555767028, rs1330793674, rs1555767169, rs201168715, rs374625613, rs942815730, rs755691417, rs2039372961, rs2039405116, rs2039247540, rs1303770209, rs398123486, rs398123490, rs398123492, rs398123496, rs398123497, rs398123499, rs398123503, rs375785084, rs398123508, rs200137189, rs398123509, rs398123513, rs398123515	RCV004571195 RCV004570920 RCV004571095 RCV005630285 RCV005630384 RCV004764804 RCV005017161 RCV000002473 RCV001175041 RCV004566673 RCV005016224 RCV001826819 RCV005608877 RCV000002474 RCV004567386 RCV005025306 RCV005019359 RCV001194035 RCV005021988 RCV004574040 RCV005021989 RCV004574041 RCV005622238 RCV005014841 RCV005014910 RCV004575398 RCV004575399 RCV004575400 RCV004575401 RCV004575402 RCV004575403 RCV004567877 RCV005018835 RCV000587694 RCV001834747 RCV001829666 RCV004568334 RCV004568341 RCV005430621 RCV001835912 RCV001829858 RCV001830465 RCV005430718 RCV005430776 RCV005430722 RCV005430752 RCV005430625 RCV004568561 RCV005430733 RCV005253051 RCV005430420 RCV004568570 RCV004568562 RCV005401692 RCV005630376 RCV005606784 RCV004570652 RCV004566948 RCV001193901 RCV000853374 RCV004566949 RCV001275909 RCV001275910 RCV004566950 RCV003982876 RCV001831820 RCV001275916 RCV004566952 RCV004813052 RCV005867857 RCV001275918	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Thyroid cancer, nonmedullary, 1	Likely pathogenic	rs756052603	RCV005934652	★★★★☆ 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	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLASSIC MAPLE SYRUP URINE DISEASE	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLASSICAL MAPLE SYRUP URINE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
INTERMEDIATE MAPLE SYRUP URINE DISEASE	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERMITTENT MAPLE SYRUP URINE DISEASE	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAPLE SYRUP URINE DISEASE, TYPE 1A	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAPLE SYRUP URINE DISEASE, TYPE IA	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THIAMIN-RESPONSIVE MAPLE SYRUP URINE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THIAMINE-RESPONSIVE MAPLE SYRUP URINE DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis	Arthritis	BEFREE	31298290		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	36417878	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Embryonal	Embryonal carcinoma	Pubtator	3025625	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36417878	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	28082671, 29130951		★☆☆☆☆ Found in Text Mining only
Classic maple syrup urine disease	Maple Syrup Urine Disease	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Classic Maple Syrup Urine Disease	Maple Syrup Urine Disease	BEFREE	29673582		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Classic Maple Syrup Urine Disease	Maple Syrup Urine Disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Crohn Disease	Crohn Disease	BEFREE	28523573		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	16757574	Associate	★☆☆☆☆ Found in Text Mining only
Eosinophilic Esophagitis	Eosinophilia	Pubtator	35897808	Associate	★☆☆☆☆ Found in Text Mining only
Fatigue Syndrome Chronic	Fatigue syndrome	Pubtator	33669532	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	24196438	Associate	★☆☆☆☆ Found in Text Mining only
Hallucinations	Hallucinations	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intermediate maple syrup urine disease	Maple Syrup Urine Disease	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intermediate Maple Syrup Urine Disease	Maple Syrup Urine Disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intermittent maple syrup urine disease	Maple Syrup Urine Disease	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intermittent Maple Syrup Urine Disease	Maple Syrup Urine Disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ketosis	Ketosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Maple Syrup Urine Disease	Maple Syrup Urine Disease	CLINVAR_DG	10694918, 10745006, 11069910, 11507102, 11825067, 14517957, 14567968, 16468966, 16786533, 17922217, 18378174, 1867199, 1885764, 19456321, 19480318, 19715473, 21098507, 21844576, 22593002, 22727569, 25087612, 25255367, 25525159, 26232051, 26257134, 26830710, 26901124, 7883996, 8037208, 8161368, 9582350		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple Syrup Urine Disease	Maple syrup urine disease	Pubtator	11112664, 11507102, 14742428, 1867199, 1885764, 19715473, 20136525, 2060625, 2316528, 24268812, 24603436, 2703538, 2914958, 29366676, 31775088, 31830945, 33131499, 33955723, 34556729, 35799415, 37248682, 7883996, 8037208, 8240269	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple Syrup Urine Disease	Maple Syrup Urine Disease	BEFREE	11486905, 19085071, 19240989, 19456321, 20431954, 22145486, 22727569, 25381949, 26453840, 28830848, 29306928, 29366676, 29740478, 31775088		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple Syrup Urine Disease	Maple Syrup Urine Disease	LHGDN	17922217, 18378174		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple Syrup Urine Disease	Maple Syrup Urine Disease	UNIPROT_DG	1867199, 1885764, 2060625, 21844576, 2241958, 2703538, 7883996, 8037208, 8161368		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple Syrup Urine Disease	Maple Syrup Urine Disease	GENOMICS_ENGLAND_DG	31112740, 9582350		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple Syrup Urine Disease	Maple Syrup Urine Disease	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maple Syrup Urine Disease, Thiamine Responsive	Maple Syrup Urine Disease	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Maple syrup urine disease, type 1A	Maple Syrup Urine Disease	CLINVAR_DG	10694918, 12888983, 14517957, 14567968, 19480318, 21098507, 21228398, 23765052, 24374108, 26830710, 2703538, 27403441, 8037208		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Maple Syrup Urine Disease, Type IA	Maple Syrup Urine Disease	GENOMICS_ENGLAND_DG	27604308		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	7525602	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	35897808	Associate	★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	16757574	Associate	★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	7525602	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rhabdomyosarcoma	Rhabdomyosarcoma	Pubtator	7525602	Associate	★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	30787184		★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	30787184		★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	28523573		★☆☆☆☆ Found in Text Mining only