UQCRB

Chr 8AR

ubiquinol-cytochrome c reductase binding protein

Also known as: MC3DN3, QCR7, QP-C, QPC, UQBC, UQBP, UQCR6, UQPC

NCBI Gene: 7381 ENSG00000156467 UniProt: P14927 OMIM: 191330

The protein is a subunit of mitochondrial respiratory complex III (ubiquinol-cytochrome c oxidoreductase) that binds ubiquinone and transfers electrons during cellular respiration. Mutations cause mitochondrial complex III deficiency, nuclear type 3, inherited in an autosomal recessive pattern. The pathogenic mechanism appears to be dominant negative, where mutant proteins disrupt normal complex III function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. This protein plays an important role in hypoxia-induced angiogenesis through mitochondrial reactive oxygen species-mediated signaling. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.081 OMIM phenotype

Clinical Summary— UQCRB

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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 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 32 VUS of 98 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?

1.08LOEUF

pLI 0.016

Z-score 1.43

OE 0.47 (0.23–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.19Z-score

OE missense 0.94 (0.77–1.15)

69 obs / 73.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.23–1.08)

0≤0.351.4

Missense OE?0.94 (0.77–1.15)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 4 / 8.5Missense obs/exp: 69 / 73.5Syn Z: 0.15

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongUQCRB-related mitochondrial respiratory chain complex III deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.75top 25%

GOF

0.5856th %ile

LOF

0.2580th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS32

Likely Benign34

Benign10

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	1	2	0	0	3
VUS	2	26	4	0	32
Likely Benign	0	3	26	5	34
Benign	0	0	8	2	10
Conflicting	—				4
Total	4	31	38	7	84

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap UQCRB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →