UQCRC1

Chr 3AD

ubiquinol-cytochrome c reductase core protein 1

Also known as: D3S3191, PKNPY, QCR1, UQCR1

NCBI Gene: 7384ENSG00000010256UniProt: P31930OMIM: 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).

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.551 OMIM phenotype
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
14 unique Pathogenic / Likely Pathogenic· 86 VUS of 122 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
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 OE0.30 (0.18–0.55)
0≤0.351.4
Missense OE0.91 (0.82–1.01)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 8 / 26.4Missense obs/exp: 275 / 302.2Syn Z: -1.07
DN
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

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS86
Likely Benign4
11
Pathogenic
3
Likely Pathogenic
86
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
8
0
11
Likely Pathogenic
0
2
1
0
3
VUS
0
84
2
0
86
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total191120104

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

View in ClinVar →

Protein Context — Lollipop Plot

UQCRC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients