UQCRQ

Chr 5AR

ubiquinol-cytochrome c reductase complex III subunit VII

Also known as: MC3DN4, QCR8, QP-C, QPC, UQCR7

NCBI Gene: 27089 ENSG00000164405 UniProt: O14949 OMIM: 612080

The protein is a ubiquinone-binding subunit of mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase), functioning in cellular energy production. Autosomal recessive mutations cause mitochondrial complex III deficiency, nuclear type 4. The pathogenic mechanism involves dominant-negative effects disrupting complex III assembly or function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a ubiquinone-binding protein of low molecular mass. This protein is a small core-associated protein and a subunit of ubiquinol-cytochrome c reductase complex III, which is part of the mitochondrial respiratory chain. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex III deficiency, nuclear type 4MIM #615159

Clinical highlights

Gene–disease validity (ClinGen)

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.69

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.048

Z-score 0.63

OE 0.62 (0.25–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.42Z-score

OE missense 0.83 (0.65–1.08)

42 obs / 50.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.25–1.69)

0≤0.351.4

Missense OE?0.83 (0.65–1.08)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 2 / 3.2Missense obs/exp: 42 / 50.3Syn Z: -0.43

Background carrier burden — how many people carry a rare variant somewhere in UQCRQ?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 630

122 rare PASS variants

Rare truncating (LoF)

1 in 14,000

23 rare PASS variants

Rare synonymous (reference)

1 in 290

54 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UQCRQ. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 860	1 in 13,000
South Asian	~43k	1 in 870	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 570	≈ 1 in 15,000
European (Finnish)	~27k	≈ 1 in 8,900	≈ 1 in 27,000
Admixed American	~22k	1 in 530	≈ 1 in 22,000
African / African American	~21k	1 in 400	≈ 1 in 17,000
East Asian	~20k	1 in 1,500	none seen
Ashkenazi Jewish	~13k	1 in 1,500	none seen
Middle Eastern	~2,884	1 in 480	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓