CYBC1
Chr 17ARcytochrome b-245 chaperone 1
Also known as: C17orf62, CGD5, Eros
Involved in innate immune response and respiratory burst after phagocytosis. Located in endoplasmic reticulum. Implicated in autosomal recessive chronic granulomatous disease 5. [provided by Alliance of Genome Resources, Jul 2025]
Primary Disease Associations & Inheritance
Chronic granulomatous disease 5, autosomal recessiveMIM #618935
AR
Clinical Summary— CYBC1
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
27 Pathogenic / Likely Pathogenic· 73 VUS of 217 total submissions
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Open GeneReview ↗GeneReview available — CYBC1
Authoritative clinical overview · Recommended first read
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.31LOEUF
pLI 0.001
Z-score 0.93
OE 0.67 (0.36–1.31)
Highly tolerant — LoF variants common in population
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.47Z-score
OE missense 0.87 (0.74–1.04)
96 obs / 109.8 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.67 (0.36–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.74–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 6 / 9.0Missense obs/exp: 96 / 109.8Syn Z: -0.63
ClinVar Variant Classifications
217 submitted variants in ClinVar
Classification Summary
Pathogenic22
Likely Pathogenic5
VUS73
Likely Benign94
Benign22
Conflicting1
22
Pathogenic
5
Likely Pathogenic
73
VUS
94
Likely Benign
22
Benign
1
Conflicting
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 21 | 0 | 22 |
Likely Pathogenic | 2 | 0 | 3 | 0 | 5 |
VUS | 4 | 50 | 18 | 1 | 73 |
Likely Benign | 0 | 2 | 49 | 43 | 94 |
Benign | 0 | 2 | 17 | 3 | 22 |
Conflicting | — | 1 | |||
| Total | 7 | 54 | 108 | 47 | 217 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CYBC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
CYTOCHROME b(-254) CHAPERONE 1; CYBC1
MIM #618334 · *
Autosomal recessive
External Resources
Links to major genomics databases and tools
📖
Open GeneReview ↗GeneReview available — CYBC1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
Characterization of AR-CGD female patient with a novel homozygous deletion in CYBC1 gene presenting with unusual clinical phenotype.
Chiriaco M et al.·Clin Immunol
2023Case report
First Report on Chronic Granulomatous Disease from Nepal and a Review of CYBC1 Deficiency.
Bhattarai D et al.·J Clin Immunol
2024Review
HSCT in two brothers with CGD arising from mutations in CYBC1 corrects the defect in neutrophil function.
Perez-Heras I et al.·Clin Immunol
2021Case report
De Novo Somatic Mosaicism of CYBB Caused by Intronic LINE-1 Element Insertion Resulting in Chronic Granulomatous Disease.
Yu L et al.·J Clin Immunol
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
CYBC1 Drives Glioblastoma Progression via Reactive Oxygen Species and NF-κB Pathways.
Kim HJ et al.·Cancer Res Treat
2025Open Access
A novel mutation in EROS (CYBC1) causes chronic granulomatous disease.
Mortimer PM et al.·Clin Immunol
2023
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Constructing a prognostic model for hepatocellular carcinoma based on bioinformatics analysis of inflammation-related genes
Li Y et al.·Front Med (Lausanne)
2024Functional
Single-Cell RNA Sequencing Integrated with Bulk-RNA Sequencing Analysis Reveals Prognostic Signatures Based on PANoptosis in Hepatocellular Carcinoma
Wang J et al.·J Hepatocell Carcinoma
2025
Hematologically important mutations: The autosomal forms of chronic granulomatous disease (third update).
Roos D et al.·Blood Cells Mol Dis
2021
Optimizing the diagnosis of chronic granulomatous disease using dihydrorhodamine-123 assay: Lessons from a large monocentric cohort.
Oiuna L et al.·Cytometry B Clin Cytom
2026Cohort
Haematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease
Slatter MA et al.·J Clin Med
2023
Top 5 full-text resultsSearch PubTator3 ↗
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools