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…

DNmechanismARLOEUF 0.641 OMIM phenotype

Clinical Summary— CYC1

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 101 VUS of 185 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.139

Z-score 2.53

OE 0.28 (0.14–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.97 (0.86–1.10)

169 obs / 173.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.14–0.64)

0≤0.351.4

Missense OE?0.97 (0.86–1.10)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 4 / 14.3Missense obs/exp: 169 / 173.7Syn Z: -2.33

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCYC1-related mitochondrial complex III deficiency, nuclearOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6840th %ile

GOF

0.4480th %ile

LOF

0.3745th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS101

Likely Benign59

Benign16

Conflicting1

Pathogenic

101

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	3	94	1	3	101
Likely Benign	1	2	25	31	59
Benign	0	1	12	3	16
Conflicting	—				1
Total	4	99	38	37	179

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap CYC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →