UQCRH

Chr 1AR

ubiquinol-cytochrome c reductase hinge protein

Also known as: MC3DN11, QCR6, UQCR8

NCBI Gene: 7388 ENSG00000173660 UniProt: P07919 OMIM: 613844

The protein is a component of mitochondrial complex III (ubiquinol-cytochrome c oxidoreductase), which transfers electrons from ubiquinol to cytochrome c as part of the electron transport chain that drives ATP synthesis. Mutations cause mitochondrial complex III deficiency with autosomal recessive inheritance. The gene shows low constraint against loss-of-function variants (pLI 0.002, LOEUF 1.347), suggesting tolerance to heterozygous inactivation consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables ubiquinol-cytochrome-c reductase activity. Predicted to be involved in mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrial inner membrane. Implicated in mitochondrial complex III deficiency. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.351 OMIM phenotype

Clinical Summary— UQCRH

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 13 VUS of 24 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.002

Z-score 0.92

OE 0.64 (0.34–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.17Z-score

OE missense 0.94 (0.74–1.19)

49 obs / 52.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.34–1.35)

0≤0.351.4

Missense OE?0.94 (0.74–1.19)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 5 / 7.8Missense obs/exp: 49 / 52.4Syn Z: -0.30

This gene — mechanism propensity

0.6647th %ile

GOF

0.74top 25%

LOF

0.1299th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

24 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS13

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	1	0	1
Likely Pathogenic	0	0	0
VUS	1	12	13
Likely Benign	0	0	0
Benign	0	0	0
Total	2	12	14

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

View in ClinVar →

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