UQCC4

Chr 16

ubiquinol-cytochrome c reductase complex assembly factor 4

Also known as: C16orf91, CCSMST1, URLC5, gs103

NCBI Gene: 283951 ENSG00000174109 UniProt: Q4G0I0 OMIM: 620578

The UQCC4 protein is required for assembly and stability of mitochondrial respiratory chain complex III, a key component of the electron transport chain that drives oxidative phosphorylation. Mutations cause mitochondrial complex III deficiency, which presents with variable combinations of neurological, cardiac, and multi-organ dysfunction. The gene shows autosomal recessive inheritance and is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in mitochondrial respiratory chain complex III assembly. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.83

Clinical Summary— UQCC4

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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

2 total variants — no pathogenic classifications of 2 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?

1.83LOEUF

pLI 0.000

Z-score -0.93

OE 1.28 (0.86–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.38Z-score

OE missense 1.07 (0.96–1.20)

227 obs / 211.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.28 (0.86–1.83)

0≤0.351.4

Missense OE?1.07 (0.96–1.20)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 16 / 12.5Missense obs/exp: 227 / 211.6Syn Z: -1.50

This gene — mechanism propensity

0.6357th %ile

GOF

0.6931th %ile

LOF

0.2874th %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

2 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

46 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap UQCC4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →