CYBC1

protein-coding

cytochrome b-245 chaperone 1

Gene summary

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]

Previous symbols:

C17orf62

MANE transcript

NM_001033046.4

Inheritance

ClinVar variants

P:6U:57B:51

Top phenotype

Granulomatous disease, chronic, autosomal recessive, 5

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr17:82,440,912-82,450,829

External References & Databases

Ensembl (ENSG00000178927)

Transcript & Mutation Effects

hg38 • Region Span ~9.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

chronic granulomatous diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018305

Submitter: Orphanet

granulomatous disease, chronic, autosomal recessive, 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030066

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Granulomatous disease, chronic, autosomal recessive, 5AR

Manifestation: Allergy/Immunology/Infectious; Musculoskeletal

Intervention: Allergy/Immunology/Infectious

Rationale: Surveillance for infections and infectious complications is indicated, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation

Refs: 28600779; 30312704; 30361506

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYBC1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 169

not specifiedTotal: 19

Granulomatous disease, chronic, autosomal recessive, 5Total: 5

CYBC1-related conditionTotal: 1

CYBC1-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001033046.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	46 clinvar		47
missense			51 clinvar	4 clinvar	1 clinvar	56
nonsense	2 clinvar					2
start loss			1 clinvar			1
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)		3 clinvar	2 clinvar			5
Total	3	3	57	50	1	114

Highest pathogenic variant AF is 0.000011160645

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 131 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001033046.4	RefSeq	NP_001028218.1	6	MANE Select
ENST00000306645.10	Ensembl	ENSP00000307765.5	6	MANE Select
NM_001100407.3	RefSeq	NP_001093877.1	6	Standard
NM_001100408.3	RefSeq	NP_001093878.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

innate immune response
respiratory burst after phagocytosis

Molecular Function

protein binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000437807
Coding exons: 6
Length: 8241
Individuals with no LoFs: 125694
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125707
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.469	96	110	0.874	0.00000666	1203
Missense (PolyPhen)		33	42.836	0.77037		474
Synonymous	-0.631	53	47.5	1.12	0.00000312	371
Loss of Function	0.926	6	9.00	0.667	3.82e-7	109

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000070	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 hetrodimer. Controls the phagocyte respiratory burst and is essential for innate immunity. {ECO:0000250|UniProtKB:Q3TYS2}.;

Intolerance Scores

RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (gene trap): N