CYB5R4
protein-codingcytochrome b5 reductase 4
Gene summary
NCB5OR is a flavohemoprotein that contains functional domains found in both cytochrome b5 (CYB5A; MIM 613218) and CYB5 reductase (CYB5R3; MIM 613213) (Zhu et al., 1999 [PubMed 10611283]).[supplied by OMIM, Jan 2010]
- NCB5OR
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~107.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CYB5R4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016230.4. 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 | 1 | ||||
| missense | 81 | 3 | 1 | 85 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 89 | 3 | 1 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057314.2 | 16 | MANE Select | |
| Ensembl | ENSP00000358695.3 | 16 | MANE Select | |
| Ensembl | ENSP00000358693.4 | 4 | Standard | |
| Ensembl | ENSP00000536335.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amino sugar and nucleotide sugar metabolism - Homo sapiens (human)
- Oxidation by Cytochrome P450
- O2/CO2 exchange in erythrocytes
- Transport of small molecules
- Erythrocytes take up carbon dioxide and release oxygen
Biological Process
- detection of oxygen
- generation of precursor metabolites and energy
- superoxide metabolic process
- bicarbonate transport
- insulin secretion
Molecular Function
- cytochrome-b5 reductase activity, acting on NAD(P)H
- NAD(P)H oxidase activity
- oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor
- heme binding
- metal ion binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369681
- Coding exons
- 16
- Length
- 107782
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125744
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.739 | 224 | 257 | 0.870 | 0.0000120 | 3428 |
| Missense (PolyPhen) | 73 | 97.489 | 0.7488 | 1276 | ||
| Synonymous | -0.0420 | 87 | 86.5 | 1.01 | 0.00000403 | 930 |
| Loss of Function | 1.80 | 18 | 28.4 | 0.635 | 0.00000127 | 394 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00018 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS). Reduces a variety of substrates in vitro, such as cytochrome c, feericyanide and methemoglobin.;
Intolerance Scores
- LoFtool
- 0.335
- RVIS EVS
- 0.28
- RVIS percentile EVS
- 71.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.700
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |