UQCRC1

Chr 3

ubiquinol-cytochrome c reductase core protein 1

Also known as: D3S3191, PKNPY, QCR1, UQCR1

NCBI Gene: 7384 ENSG00000010256 UniProt: P31930

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 ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by Alliance of Genome Resources, Apr 2025]

GeneReviews ResearchGenerating clinical summary…

DNmechanismLOEUF 0.55

Clinical Summary— UQCRC1

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ADDisputed

Disputed — evidence questions this relationship

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 84 VUS of 111 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — UQCRC1

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

This gene — mechanism propensity

0.7230th %ile

GOF

0.5169th %ile

LOF

0.2775th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic2

VUS84

Likely Benign4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	1	2	0	3
Likely Pathogenic	0	2	0	2
VUS	0	84	0	84
Likely Benign	0	3	1	4
Benign	0	0	0	0
Total	1	91	1	93

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap UQCRC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →