CYC1

Chr 8AR

cytochrome c1

Also known as: MC3DN6, UQCR4

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]

Primary Disease Associations & Inheritance

Mitochondrial complex III deficiency, nuclear type 6MIM #615453
AR
1
Active trials
28
Pubs (1 yr)
65
P/LP submissions
3%
P/LP missense
0.64
LOEUF
DN
Mechanism· predicted
Clinical SummaryCYC1
🧬
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.
📋
ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 112 VUS of 256 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

256 submitted variants in ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic5
VUS112
Likely Benign58
Benign16
Conflicting1
58
Pathogenic
5
Likely Pathogenic
112
VUS
58
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
93
13
3
112
Likely Benign
1
2
24
31
58
Benign
0
1
12
3
16
Conflicting
1
Total49811037250

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.

Clinical Literature
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