UQCC3

Chr 11AR

ubiquinol-cytochrome c reductase complex assembly factor 3

NCBI Gene: 790955 ENSG00000204922 UniProt: Q6UW78 OMIM: 616097

The UQCC3 protein is required for assembly of mitochondrial respiratory chain complex III, mediating cytochrome b recruitment and stabilization within the complex that transfers electrons from ubiquinol to cytochrome c for ATP production. Mutations cause mitochondrial complex III deficiency, nuclear type 9, which follows autosomal recessive inheritance. The gene shows relatively low constraint to loss-of-function variation, consistent with recessive disease requiring biallelic mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex), mediating cytochrome b recruitment and probably stabilization within the complex. Thereby, plays an important role in ATP production by mitochondria. Cardiolipin-binding protein, it may also control the cardiolipin composition of mitochondria membranes and their morphology

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Mitochondrial complex III deficiency, nuclear type 9MIM #616111

Clinical highlights

Gene–disease validity (ClinGen)

Limited · mitochondrial disease · AR · ClinGen 2024

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.82

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.032

Z-score 0.27

OE 0.82 (0.31–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.97 (0.78–1.22)

53 obs / 54.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.31–1.82)

0≤0.351.4

Missense OE?0.97 (0.78–1.22)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 2 / 2.5Missense obs/exp: 53 / 54.8Syn Z: 0.43

Background carrier burden — how many people carry a rare variant somewhere in UQCC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

146 rare PASS variants

Rare truncating (LoF)

1 in 7,100

22 rare PASS variants

Rare synonymous (reference)

1 in 2,000

63 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UQCC3. 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 480	1 in 9,100
South Asian	~43k	1 in 1,300	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 970	≈ 1 in 30,000
European (Finnish)	~27k	1 in 3,300	none seen
Admixed American	~22k	1 in 260	1 in 1,200
African / African American	~21k	1 in 350	1 in 1,700
East Asian	~20k	1 in 290	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 4,400	none seen
Middle Eastern	~2,884	≈ 1 in 960	≈ 1 in 2,700

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 ↓