CYC1

Chr 8AR

cytochrome c1

Also known as: MC3DN6, UQCR4

NCBI Gene: 1537 ENSG00000179091 UniProt: P08574 OMIM: 123980

The CYC1 protein is a catalytic core subunit of mitochondrial respiratory chain complex III (cytochrome bc1 complex) that transfers electrons from the Rieske iron-sulfur protein to cytochrome c during oxidative phosphorylation. Autosomal recessive mutations cause mitochondrial complex III deficiency, nuclear type 6, a disorder affecting cellular energy production. The gene shows moderate constraint to loss-of-function variants (LOEUF 0.639), consistent with its essential role in mitochondrial respiration.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of the cytochrome bc1 complex, which plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c. Mutations in this gene may cause mitochondrial complex III deficiency, nuclear type 6. [provided by RefSeq, Dec 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex III deficiency, nuclear type 6MIM #615453

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · mitochondrial disease · AR · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in CYC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

496 rare PASS variants

Rare truncating (LoF)

1 in 4,300

49 rare PASS variants

Rare synonymous (reference)

1 in 260

235 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CYC1. 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 190	1 in 4,700
South Asian	~43k	1 in 130	none seen
Remaining (unassigned)	~30k	1 in 150	≈ 1 in 15,000
European (Finnish)	~27k	1 in 440	1 in 720
Admixed American	~22k	1 in 130	≈ 1 in 5,600
African / African American	~21k	1 in 120	≈ 1 in 9,300
East Asian	~20k	1 in 140	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 770	none seen
Middle Eastern	~2,884	1 in 98	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): 6 of 7 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 7.? see exons ↓