UQCC4

Chr 16

ubiquinol-cytochrome c reductase complex assembly factor 4

Also known as: C16orf91, CCSMST1, URLC5, gs103

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.83
Clinical SummaryUQCC4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.83LOEUF
pLI 0.000
Z-score -0.93
OE 1.28 (0.861.83)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.38Z-score
OE missense 1.07 (0.961.20)
227 obs / 211.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.28 (0.861.83)
00.351.4
Missense OE1.07 (0.961.20)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 16 / 12.5Missense obs/exp: 227 / 211.6Syn Z: -1.50
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

UQCC4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found