CYC1

Chr 8AR

cytochrome c1

Also known as: MC3DN6, UQCR4

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.641 OMIM phenotype
Clinical SummaryCYC1
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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
63 unique Pathogenic / Likely Pathogenic· 112 VUS of 257 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.139
Z-score 2.53
OE 0.28 (0.140.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.97 (0.861.10)
169 obs / 173.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.140.64)
00.351.4
Missense OE0.97 (0.861.10)
00.61.4
Synonymous OE1.35
01.21.6
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

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

DN
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

257 submitted variants in ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic5
VUS112
Likely Benign59
Benign16
Conflicting1
58
Pathogenic
5
Likely Pathogenic
112
VUS
59
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
56
0
58
Likely Pathogenic
0
0
5
0
5
VUS
3
94
12
3
112
Likely Benign
1
2
25
31
59
Benign
0
1
12
3
16
Conflicting
1
Total49911037251

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

View in ClinVar →

Protein Context — Lollipop Plot

CYC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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