UQCRC1

Chr 3AD

ubiquinol-cytochrome c reductase core protein 1

NCBI Gene: 7384 ENSG00000010256 UniProt: P31930 OMIM: 191328

UQCRC1 encodes a core subunit of mitochondrial complex III (ubiquinol-cytochrome c oxidoreductase) that catalyzes electron transfer from ubiquinol to cytochrome c as part of the respiratory chain driving oxidative phosphorylation. Mutations cause autosomal dominant parkinsonism with polyneuropathy, reflecting the protein's important role in maintaining proper mitochondrial function in dopaminergic neurons. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.546).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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 (By similarity). 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 (By similarity). 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 (Probable). Seems to play an important role in the maintenance of proper mitochondrial function in nigral dopaminergic neurons (PubMed:33141179)

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Parkinsonism with polyneuropathyMIM #619279

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · mitochondrial disease · AD · ClinGen 2025

evidence questions this relationship

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.55

LOEUF

Mechanism· predicted

📖

GeneReview available — UQCRC1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.020

Z-score 3.32

OE 0.30 (0.18–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.56Z-score

OE missense 0.91 (0.82–1.01)

275 obs / 302.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.18–0.55)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 8 / 26.4Missense obs/exp: 275 / 302.2Syn Z: -1.07

Background carrier burden — how many people carry a rare variant somewhere in UQCRC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

656 rare PASS variants

Rare truncating (LoF)

1 in 2,300

90 rare PASS variants

Rare synonymous (reference)

1 in 150

301 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UQCRC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 2,200
South Asian	~43k	1 in 54	1 in 1,200
Remaining (unassigned)	~30k	1 in 62	≈ 1 in 7,500
European (Finnish)	~27k	1 in 220	≈ 1 in 13,000
Admixed American	~22k	1 in 68	1 in 3,800
African / African American	~21k	1 in 87	1 in 600
East Asian	~20k	1 in 160	1 in 2,800
Ashkenazi Jewish	~13k	1 in 820	none seen
Middle Eastern	~2,884	1 in 88	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓