UQCRC1

Summary

UQCRC1 (ubiquinol-cytochrome c reductase core protein 1, HGNC:12585) is a protein-coding gene on chromosome 3p21.31, encoding Cytochrome b-c1 complex subunit 1, mitochondrial (P31930). Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. It is a selective cancer dependency (DepMap: 47.9% of cell lines).

Enables ubiquitin protein ligase binding activity. Predicted to be involved in oxidative phosphorylation. Predicted to act upstream of or within mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrial inner membrane. Implicated in Alzheimer’s disease. Biomarker of Alzheimer’s disease.

Source: NCBI Gene 7384 — RefSeq curated summary.

At a glance

• Gene–disease (curated): parkinsonism with polyneuropathy (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 98 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 47.9% of screened cell lines
• MANE Select transcript: NM_003365

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12585
Approved symbol	UQCRC1
Name	ubiquinol-cytochrome c reductase core protein 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	D3S3191, QCR1, UQCR1
Ensembl gene	ENSG00000010256
Ensembl biotype	protein_coding
OMIM	191328
Entrez	7384

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 11 retained_intron, 9 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000203407, ENST00000412343, ENST00000415995, ENST00000460105, ENST00000463708, ENST00000467690, ENST00000471189, ENST00000472438, ENST00000480561, ENST00000493806, ENST00000714195, ENST00000714196, ENST00000714197, ENST00000714198, ENST00000714199, ENST00000714200, ENST00000714201, ENST00000714202, ENST00000899333, ENST00000899334, ENST00000899335, ENST00000912155, ENST00000912156, ENST00000951190, ENST00000951191

RefSeq mRNA: 1 — MANE Select: NM_003365 NM_003365

CCDS: CCDS2774

Canonical transcript exons

ENST00000203407 — 13 exons

Exon	Start	End
ENSE00001861123	48599002	48599192
ENSE00001943033	48609552	48609646
ENSE00003461543	48604651	48604780
ENSE00003475748	48601352	48601467
ENSE00003560509	48604233	48604431
ENSE00003594422	48603564	48603643
ENSE00003598610	48605770	48605856
ENSE00003605721	48600482	48600567
ENSE00003651194	48600975	48601118
ENSE00003666609	48599635	48599710
ENSE00003673838	48600063	48600151
ENSE00003676121	48609162	48609302
ENSE00003693823	48600680	48600840

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 178.5843 / max 1126.4239, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42156	178.5843	1828

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.70	gold quality
heart left ventricle	UBERON:0002084	99.53	gold quality
heart right ventricle	UBERON:0002080	99.52	gold quality
cardiac ventricle	UBERON:0002082	99.52	gold quality
triceps brachii	UBERON:0001509	99.49	gold quality
gastrocnemius	UBERON:0001388	99.35	gold quality
left ventricle myocardium	UBERON:0006566	99.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.33	gold quality
mucosa of transverse colon	UBERON:0004991	99.32	gold quality
right atrium auricular region	UBERON:0006631	99.27	gold quality
vastus lateralis	UBERON:0001379	99.25	gold quality
cardiac atrium	UBERON:0002081	99.25	gold quality
heart	UBERON:0000948	99.22	gold quality
quadriceps femoris	UBERON:0001377	99.20	gold quality
muscle of leg	UBERON:0001383	99.19	gold quality
muscle organ	UBERON:0001630	99.19	gold quality
body of tongue	UBERON:0011876	99.19	gold quality
skeletal muscle organ	UBERON:0014892	99.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.17	gold quality
gluteal muscle	UBERON:0002000	99.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.12	gold quality
rectum	UBERON:0001052	99.11	gold quality
skeletal muscle tissue	UBERON:0001134	99.11	gold quality
myocardium	UBERON:0002349	99.11	gold quality
biceps brachii	UBERON:0001507	99.05	gold quality
muscle tissue	UBERON:0002385	99.02	gold quality
diaphragm	UBERON:0001103	98.95	gold quality
transverse colon	UBERON:0001157	98.92	gold quality
duodenum	UBERON:0002114	98.92	gold quality
deltoid	UBERON:0001476	98.91	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	10.19
E-MTAB-7052	no	610.70
E-MTAB-6058	no	453.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFCP2

miRNA regulators (miRDB)

5 targeting UQCRC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-891A-3P	98.05	67.99	970

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 47.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• UQCRC1 was highly expressed in breast and ovarian tumors (PMID:16775426)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Gene expression level of UQCRC1 is significantly higher in AD patients when compared to normal controls. (PMID:26943237)
• dysregulated UQCRC1 and UQCRFS1 are involved in impaired mitochondrial electron transport chain function. (PMID:27845902)
• High miR-214-3p expression may promote osteosarcoma cell proliferation by targeting UQCRC1. (PMID:31276465)
• The lack of association between ubiquinol-cytochrome c reductase core protein I (UQCRC1) variants and Parkinson’s disease in an eastern Chinese population. (PMID:32666668)
• Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy. (PMID:33141179)
• Lack of evidence for association of UQCRC1 with Parkinson’s disease in Europeans. (PMID:33248804)
• Rare variant analysis of UQCRC1 in Chinese patients with early-onset Parkinson’s disease. (PMID:37984314)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	uqcrc1	ENSDARG00000052304
mus_musculus	Uqcrc1	ENSMUSG00000025651
rattus_norvegicus	Uqcrc1	ENSRNOG00000032134
caenorhabditis_elegans		WBGENE00011679
caenorhabditis_elegans		WBGENE00015481

Paralogs (6): NRDC (ENSG00000078618), PMPCB (ENSG00000105819), PITRM1 (ENSG00000107959), IDE (ENSG00000119912), UQCRC2 (ENSG00000140740), PMPCA (ENSG00000165688)

Protein

Protein identifiers

Cytochrome b-c1 complex subunit 1, mitochondrial — P31930 (reviewed: P31930)

Alternative names: Complex III subunit 1, Core protein I, Ubiquinol-cytochrome-c reductase complex core protein 1

All UniProt accessions (6): P31930, A0AAQ5BHK6, A0AAQ5BHL5, A0AAQ5BHN1, F8WEF1, F8WER5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c. The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties. May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III. Seems to play an important role in the maintenance of proper mitochondrial function in nigral dopaminergic neurons.

Subunit / interactions. Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1. The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)). Interacts with UQCC6. Interacts with STMP1.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Expressed in brain, including substantia nigra, striatum, cortex and cerebellum, and in spinal cord, heart, kidney, liver and muscle.

Disease relevance. Parkinsonism with polyneuropathy (PKNPY) [MIM:619279] An autosomal dominant disorder characterized by late-onset, levodopa-responsive parkinsonism with asymmetric tremor, rigidity and bradykinesia. Patients also manifest a sensorimotor polyneuropathy with variable degrees of distal legs and hands muscle atrophy and weakness, and absent deep tendon reflexes. The protein represented in this entry is involved in disease pathogenesis.

Similarity. Belongs to the peptidase M16 family. UQCRC1/QCR1 subfamily.

RefSeq proteins (1): NP_003356* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007863	Peptidase_M16_C	Domain
IPR011249	Metalloenz_LuxS/M16	Homologous_superfamily
IPR011765	Pept_M16_N	Domain
IPR050361	MPP/UQCRC_Complex	Family

Pfam: PF00675, PF05193

UniProt features (47 total): helix 22, strand 10, modified residue 6, sequence variant 4, turn 3, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9HZL	ELECTRON MICROSCOPY	2.52
9CG3	ELECTRON MICROSCOPY	2.96
5XTE	ELECTRON MICROSCOPY	3.4
5XTH	ELECTRON MICROSCOPY	3.9
5XTI	ELECTRON MICROSCOPY	17.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31930-F1	91.69	0.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 111, 138, 163, 163, 212, 248

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-9865881	Complex III assembly

MSigDB gene sets: 243 (showing top): MODULE_93, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_77, LFA1_Q6, ENK_UV_RESPONSE_KERATINOCYTE_UP, DITTMER_PTHLH_TARGETS_UP, GOBP_PROTEIN_TARGETING, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, TGACCTY_ERR1_Q2, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MODULE_149, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_MITOCHONDRIAL_ELECTRON_TRANSPORT_UBIQUINOL_TO_CYTOCHROME_C, GOBP_PROTEIN_MATURATION

GO Biological Process (7): oxidative phosphorylation (GO:0006119), mitochondrial electron transport, ubiquinol to cytochrome c (GO:0006122), aerobic respiration (GO:0009060), response to activity (GO:0014823), response to alkaloid (GO:0043279), cellular respiration (GO:0045333), proton transmembrane transport (GO:1902600)

GO Molecular Function (5): quinol-cytochrome-c reductase activity (GO:0008121), ubiquitin protein ligase binding (GO:0031625), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), respiratory chain complex III (GO:0045275), respiratory chain complex (GO:0098803), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
aerobic respiration	1
proton motive force-driven ATP synthesis	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
response to stimulus	1
response to nitrogen compound	1
energy derivation by oxidation of organic compounds	1
monoatomic cation transmembrane transport	1
electron transfer activity	1
proton transmembrane transporter activity	1
oxidoreduction-driven active transmembrane transporter activity	1
oxidoreductase activity, acting on diphenols and related substances as donors	1
active monoatomic ion transmembrane transporter activity	1
ubiquitin-like protein ligase binding	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cytochrome complex	1
respiratory chain complex	1
transmembrane transporter complex	1
oxidoreductase complex	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UQCRC1	UQCRC2	P22695	973
UQCRC1	UQCRB	P14927	964
UQCRC1	COX7A1	P24310	945
UQCRC1	CYC1	P08574	944
UQCRC1	UQCRFS1	P47985	922
UQCRC1	UQCRQ	O14949	912
UQCRC1	UQCRH	P07919	902
UQCRC1	NDUFB9	Q9Y6M9	884
UQCRC1	UQCR10	Q9UDW1	830
UQCRC1	COX5B	P10606	827
UQCRC1	NDUFA9	Q16795	806
UQCRC1	NDUFS1	P28331	796
UQCRC1	NDUFV1	P49821	782
UQCRC1	NDUFS2	O75306	760
UQCRC1	ATP5F1A	P25705	759

IntAct

220 interactions, top by confidence:

A	B	Type	Score
UQCRC1	UQCRQ	psi-mi:“MI:0915”(physical association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
UQCRQ	COX7A2L	psi-mi:“MI:0914”(association)	0.640
UQCRB	COX7A2L	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
UQCRC1	ARHGDIB	psi-mi:“MI:0915”(physical association)	0.560
EEF1G	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
UQCRC1	NPHP1	psi-mi:“MI:0915”(physical association)	0.560
PFDN2	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
PITPNA	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
TBX6	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
UQCRC1	ZNF232	psi-mi:“MI:0915”(physical association)	0.560
SOX14	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
UQCRC1	BECN1	psi-mi:“MI:0915”(physical association)	0.560
EIF2B4	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
UQCRC1	PRMT5	psi-mi:“MI:0915”(physical association)	0.560
SULT1B1	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
COMMD10	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (281): UQCRC1 (Two-hybrid), UQCRC1 (Affinity Capture-RNA), UQCRC1 (Affinity Capture-RNA), UQCRC1 (Affinity Capture-MS), UQCRC1 (Co-fractionation), UQCRC1 (Co-fractionation), UQCRC1 (Affinity Capture-MS), UQCRC1 (Two-hybrid), UQCRC1 (Proximity Label-MS), UQCRC1 (Proximity Label-MS), UQCRC1 (Proximity Label-MS), UQCRC1 (Affinity Capture-MS), UQCRC1 (Affinity Capture-MS), UQCRC1 (Affinity Capture-MS), UQCRC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1F3, A3KP37, O75439, P00337, P00339, P04642, P06151, P11913, P13491, P13743, P19858, P20069, P28492, P31800, P31930, P79912, P79913, Q00302, Q03346, Q0P5M8, Q10713, Q23295, Q3SZ71, Q42290, Q571F8, Q5R1W9, Q5R513, Q5R5F0, Q5RBS1, Q5REK3, Q68FY0, Q6DGK2, Q8VY06, Q98SK9, Q98SL0, Q9BE24, Q9CXT8, Q9CZ13, Q9DC61, Q9LJL3

Diamond homologs: A0A1D8PP59, P07256, P11913, P31930, Q00302, Q9P7X1, Q9Y8B5, B8B0E2, F4HNU6, O14077, O75439, P31800, P31828, P45181, Q03346, Q3SZ71, Q40983, Q5REK3, Q68FY0, Q69TY5, Q8Z418, Q8ZMB5, Q9CXT8, Q9CZ13, Q9FIH8, O05945, O31766, O32965, O86835, P0A5S9, P10507, P9WHT4, P9WHT5, Q04805, Q1RJ61, Q42290, Q4UML9, Q4W6B5, Q68XF0, Q92IX7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UQCRC1	“form complex”	“CoQ-cytochrome c reductase-Mitochondrial respiratory chain complex III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex III assembly	5	22.4×	6e-04
Respiratory electron transport	14	13.6×	7e-10
Mitochondrial protein degradation	7	8.2×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
cellular respiration	7	25.2×	9e-06
aerobic respiration	7	14.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

98 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	73
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1064663	NM_003365.3(UQCRC1):c.941A>C (p.Tyr314Ser)	Pathogenic
1064664	NM_003365.3(UQCRC1):c.931A>C (p.Ile311Leu)	Pathogenic
2506569	NM_003365.3(UQCRC1):c.359T>C (p.Leu120Pro)	Likely pathogenic
801349	NM_003365.3(UQCRC1):c.826C>T (p.Arg276Cys)	Likely pathogenic

SpliceAI

1772 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48599189:GGGC:G	acceptor_gain	1.0000
3:48599192:CCT:C	acceptor_loss	1.0000
3:48599193:C:CA	acceptor_loss	1.0000
3:48599193:C:CC	acceptor_gain	1.0000
3:48599630:CTTA:C	donor_loss	1.0000
3:48599631:TTAC:T	donor_loss	1.0000
3:48599632:TAC:T	donor_loss	1.0000
3:48599633:A:AC	donor_gain	1.0000
3:48599633:A:AT	donor_loss	1.0000
3:48599634:C:CG	donor_gain	1.0000
3:48600076:T:A	donor_gain	1.0000
3:48600152:C:CC	acceptor_gain	1.0000
3:48600675:CTTAC:C	donor_loss	1.0000
3:48600677:TACCA:T	donor_loss	1.0000
3:48600678:A:AC	donor_gain	1.0000
3:48600678:A:AT	donor_loss	1.0000
3:48600679:C:CA	donor_loss	1.0000
3:48600679:C:CC	donor_gain	1.0000
3:48600679:CCA:C	donor_gain	1.0000
3:48600836:AGGTG:A	acceptor_gain	1.0000
3:48600837:GGTG:G	acceptor_gain	1.0000
3:48600839:TG:T	acceptor_gain	1.0000
3:48600841:C:CA	acceptor_loss	1.0000
3:48600841:C:CC	acceptor_gain	1.0000
3:48600845:C:CT	acceptor_gain	1.0000
3:48600937:C:A	donor_gain	1.0000
3:48600968:CACT:C	donor_loss	1.0000
3:48600969:ACTC:A	donor_loss	1.0000
3:48600971:T:TC	donor_loss	1.0000
3:48600972:C:CC	donor_loss	1.0000

AlphaMissense

3122 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48600681:A:G	W376R	0.998
3:48600681:A:T	W376R	0.998
3:48601073:C:G	A290P	0.998
3:48601364:G:C	F270L	0.998
3:48601364:G:T	F270L	0.998
3:48601366:A:G	F270L	0.998
3:48601072:G:T	A290E	0.997
3:48604283:G:C	F192L	0.997
3:48604283:G:T	F192L	0.997
3:48604285:A:G	F192L	0.997
3:48601365:A:G	F270S	0.996
3:48604287:G:T	A191E	0.996
3:48605847:A:G	W74R	0.996
3:48605847:A:T	W74R	0.996
3:48609193:G:T	A60D	0.996
3:48599192:C:T	G460D	0.995
3:48599635:C:G	G460R	0.995
3:48600124:C:T	G414E	0.995
3:48601079:C:G	A288P	0.995
3:48600137:A:G	C410R	0.994
3:48604284:A:G	F192S	0.994
3:48604299:A:G	L187P	0.994
3:48599640:C:T	G458E	0.993
3:48599641:C:G	G458R	0.993
3:48599641:C:T	G458R	0.993
3:48599680:A:G	C445R	0.993
3:48600135:A:C	C410W	0.993
3:48600775:G:C	F344L	0.993
3:48600775:G:T	F344L	0.993
3:48600777:A:G	F344L	0.993

dbSNP variants (sampled 300 via entrez): RS1000865571 (3:48602155 A>G), RS1000954007 (3:48607176 G>C), RS1001484563 (3:48601913 G>A), RS1001714750 (3:48607884 G>A), RS1001744249 (3:48608208 A>AT), RS1001875036 (3:48598976 C>T), RS1002636950 (3:48600472 T>C), RS1002746804 (3:48606887 G>A,C), RS1003050707 (3:48610885 C>G,T), RS1003544448 (3:48600243 C>G), RS1003600684 (3:48611548 C>G,T), RS1003721234 (3:48605019 G>A,C), RS1003874087 (3:48602906 T>C), RS1003881377 (3:48601526 G>A,T), RS1003929032 (3:48601763 T>A,C)

Disease associations

OMIM: gene MIM:191328 | disease phenotypes: MIM:619279

GenCC curated gene-disease

Disease	Classification	Inheritance
parkinsonism with polyneuropathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Disputed	AD

Mondo (2): parkinsonism with polyneuropathy (MONDO:0036193), hypertrophic cardiomyopathy (MONDO:0005045)

Orphanet (2): Parkinsonism with polyneuropathy (Orphanet:611237), Rare hypertrophic cardiomyopathy (Orphanet:217569)

HPO phenotypes

14 total (15 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001271	Polyneuropathy
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002322	Resting tremor
HP:0002506	Diffuse cerebral atrophy
HP:0002548	Parkinsonism with favorable response to dopaminergic medication
HP:0003431	Decreased motor nerve conduction velocity
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0007078	Decreased amplitude of sensory action potentials
HP:0033383	Decreased compound muscle action potential amplitude
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST009391_106	Metabolite levels	8.000000e-07
GCST009391_238	Metabolite levels	6.000000e-06
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST90002400_357	Plateletcrit	9.000000e-21
GCST90002402_308	Platelet count	1.000000e-11
GCST90020025_1948	Waist-to-hip ratio adjusted for BMI	5.000000e-10
GCST90020027_104	Waist-hip index	1.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0010491	glycocholate measurement
EFO:0010493	glycodeoxycholate measurement
EFO:0004346	neuroimaging measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066918 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.29	Kd	5.13	nM	CHEMBL5653589
8.29	ED50	5.13	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149735: Binding affinity to human UQCRC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0051	uM

CTD chemical–gene interactions

66 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects splicing, decreases expression, affects cotreatment, increases abundance	4
bisphenol A	decreases expression, increases expression	3
Arsenic	increases expression, decreases expression, increases abundance, affects cotreatment	3
Resveratrol	decreases reaction, increases expression, increases reaction	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Atrazine	decreases expression	2
Tunicamycin	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
cobaltiprotoporphyrin	decreases reaction, increases expression	1
deoxynivalenol	decreases expression	1
nobiletin	decreases reaction, decreases expression	1
sodium arsenate	decreases expression, decreases reaction	1
arsenite	affects binding, increases reaction	1
8-bromocyclic GMP	increases expression, decreases reaction	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
tin protoporphyrin IX	increases expression, increases reaction, decreases reaction	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1
brequinar	decreases expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one	increases expression, decreases reaction	1
S-nitro-N-acetylpenicillamine	decreases reaction, increases expression	1
K 7174	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652777	Binding	Binding affinity to human UQCRC1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1MA	IBMS-iPSC-057-05	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

227 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	PHASE2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	PHASE2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	PHASE2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	PHASE2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	PHASE2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	PHASE2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
NCT01230918	PHASE2	TERMINATED	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis
NCT01447654	PHASE2	COMPLETED	Inhibition of the Renin Angiotensin System With Losartan in Patients With Hypertrophic Cardiomyopathy
NCT01696370	PHASE2	UNKNOWN	Trimetazidine Therapy in Hypertrophic Cardiomyopathy
NCT01912534	PHASE2	COMPLETED	Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM
NCT02590809	PHASE2	COMPLETED	Hypertrophic Cardiomyopathy Symptom Release by BX1514M
NCT03496168	PHASE2	COMPLETED	Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in PIONEER
NCT03532802	PHASE2	COMPLETED	The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
NCT03832660	PHASE2	COMPLETED	Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy
NCT04219826	PHASE2	COMPLETED	Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy
NCT04426578	PHASE2	UNKNOWN	Role of Perhexiline in Hypertrophic Cardiomyopathy