UQCRC2

Chr 16AR

ubiquinol-cytochrome c reductase core protein 2

Also known as: MC3DN5, QCR2, UQCR2

NCBI Gene: 7385ENSG00000140740UniProt: P22695

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]

Primary Disease Associations & Inheritance

Mitochondrial complex III deficiency, nuclear type 5MIM #615160
AR
312
ClinVar variants
78
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UQCRC2
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
78 Pathogenic / Likely Pathogenic· 135 VUS of 312 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.19
OE 0.52 (0.34–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.95Z-score
OE missense 0.83 (0.74–0.93)
207 obs / 249.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.34–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.74–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 13 / 24.8Missense obs/exp: 207 / 249.3Syn Z: 0.64

ClinVar Variant Classifications

312 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic20
VUS135
Likely Benign74
Benign18
Conflicting7
58
Pathogenic
20
Likely Pathogenic
135
VUS
74
Likely Benign
18
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
56
0
58
Likely Pathogenic
4
1
15
0
20
VUS
4
80
51
0
135
Likely Benign
0
3
46
25
74
Benign
0
3
14
1
18
Conflicting
—7
Total88918226312

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

View in ClinVar →

Protein Context — Lollipop Plot

UQCRC2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex III deficiency, nuclear type 5

MIM #615160

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — UQCRC2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
Tostes K et al.·Autophagy
2022
Alternative mitochondrial quality control mediated by extracellular release.
Choong CJ et al.·Autophagy
2021
Novel pathogenic UQCRC2 variants in a female with normal neurodevelopment.
Abou Haidar L et al.·Cold Spring Harb Mol Case Stud
2024
3D culture inhibits replicative senescence of SCAPs via UQCRC2-mediated mitochondrial oxidative phosphorylation.
Shi Y et al.·J Transl Med
2024
Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress.
Le Bacquer O et al.·Am J Physiol Cell Physiol
2024
Proteomic Analysis Reveals Oxidative Phosphorylation and JAK-STAT Pathways Mediated Pathogenesis of Pemphigus Vulgaris.
Cheng Y et al.·Exp Dermatol
2024
Baicalin triggers ferroptosis to suppress colorectal cancer via SLC25A28-UQCRC2-regulated electron transport chain disruption.
Yao X et al.·Free Radic Biol Med
2026
UQCRC2-related mitochondrial complex III deficiency, about 7 patients.
Bansept C et al.·Mitochondrion
2023Cohort
Increased male fertility using fertility-related biomarkers.
Kwon WS et al.·Sci Rep
2015
Preadipocytes of obese humans display gender-specific bioenergetic responses to glucose and insulin.
Keuper M et al.·Mol Metab
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools