UQCRC2

Chr 16AR

ubiquinol-cytochrome c reductase core protein 2

Also known as: MC3DN5, QCR2, UQCR2

NCBI Gene: 7385 ENSG00000140740 UniProt: P22695 OMIM: 191329

The protein is a core subunit of mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase), essential for cellular energy production through oxidative phosphorylation. Biallelic mutations cause mitochondrial complex III deficiency nuclear type 5, inherited in an autosomal recessive pattern. The pathogenic mechanism involves loss of protein function leading to impaired mitochondrial respiration.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is located in the mitochondrion, where it is part of the ubiquinol-cytochrome c reductase complex (also known as complex III). This complex constitutes a part of the mitochondrial respiratory chain. Defects in this gene are a cause of mitochondrial complex III deficiency nuclear type 5. [provided by RefSeq, Jul 2015]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.831 OMIM phenotype

Clinical Summary— UQCRC2

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.19

OE 0.52 (0.34–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.95Z-score

OE missense 0.83 (0.74–0.93)

207 obs / 249.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.34–0.83)

0≤0.351.4

Missense OE?0.83 (0.74–0.93)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 13 / 24.8Missense obs/exp: 207 / 249.3Syn Z: 0.64

This gene — mechanism propensity

0.7228th %ile

GOF

0.4777th %ile

LOF

0.3745th %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.