• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CYBB (HGNC:2578) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
cytochrome b-245 beta chain
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
CGD
Alias symbols
GP91-PHOX, NOX2, GP91PHOX, p91-PHOX
%HI
10.63(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.19(Read more about gnomAD LOEUF score)
Cytoband
Xp21.1-p11.4
Genomic Coordinates
GRCh37/hg19: chrX:37639312-37672714 NCBI Ensembl UCSC
GRCh38/hg38: chrX:37780059-37813461 NCBI Ensembl UCSC
MANE Select Transcript
NM_000397.4 ENST00000378588.5 (Read more about MANE Select)
Function
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-6894
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
05/27/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • granulomatous disease, chronic, X-linked Monarch
HI Evidence Comments:
Mutations in CYBB are the most common causes of chronic granulomatous disease (CGD). A large number of variants (>600) have been reported for CYBB that cause the X-linked form of CGD. A large-scale review of variation within this gene demonstrates variants ranging from single nucleotide variations to deletions of several megabases (PMID: 20729109). The majority are loss of function variants (e.g. 75% are nonsense, del/dup, splicing variants (PMID: 30716179) and about 12–15% of the mutations in CYBB result from de novo mutations ((PMID: 20729109), thus there are overwhelming case and genetic evidence supporting haploinsufficiency of CYBB. Some female carriers have been shown to manifest a disease phenotype. See GeneReviews for relevant primary literature and review, as well as a discussion of known genotype-phenotype correlations. Of note, intragenic duplications have been identified in patients with CGD, likely due to a loss of function mechanism (PMID:22924696, 22382877).
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Focal whole gene duplications have not been reported in association with CGD or other phenotypes; however, intragenic duplications have been identified in patients with CGD, likely due to a loss of function mechanism.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)