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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CYB5A
cytochrome b5 type A
Chromosome 18 · 18q22.3
NCBI Gene: 1528Ensembl: ENSG00000166347.20HGNC: HGNC:2570UniProt: A0A384ME44
109PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolenzyme bindingmembraneprotein bindinghereditary methemoglobinemiaAbnormality of the skeletal system46,XY disorder of sex development due to isolated 17,20 lyase deficiencymethemoglobinemia due to deficiency of methemoglobin reductase
✦AI Summary

CYB5A encodes cytochrome b5 type A, a membrane-bound hemoprotein that functions as an electron carrier for various oxygenases. The protein plays crucial roles in steroidogenesis by enhancing CYP17A1's 17,20-lyase activity, which is essential for androgen biosynthesis 1. CYB5A demonstrates functional redundancy with CYB5B in cholesterol biosynthesis, specifically in sterol C4-demethylation, where either protein can compensate for the other's absence 2. In the human adrenal cortex, CYB5A co-localizes with HSD3B2 at the border between zona fasciculata and reticularis, contributing to androstenedione production 3. The protein also exhibits tumor suppressor properties in pancreatic cancer by inducing autophagy-mediated cell death 4. Additionally, CYB5A participates in carcinogen detoxification pathways, with genetic variants potentially influencing breast cancer risk, particularly in African American populations 5. Despite its role in androgen synthesis, CYB5A polymorphisms showed no significant association with polycystic ovary syndrome in South Indian populations 6, and mixed results regarding treatment response in rheumatoid arthritis patients 78.

Sources cited
1
CYB5A stimulates CYP17A1's 17,20-lyase reaction and is required for androgen biosynthesis
PMID: 31509771
2
CYB5A and CYB5B compensate for each other in sterol C4-demethylation during cholesterol biosynthesis
PMID: 39489939
3
CYB5A co-expresses with HSD3B2 in human adrenal cortex cells contributing to androstenedione production
PMID: 21185375
4
CYB5A demonstrates tumor suppressor activity through autophagy induction in pancreatic cancer
PMID: 24448000
5
CYB5A participates in carcinogen detoxification and variants may influence breast cancer risk
PMID: 25225034
6
CYB5A polymorphisms showed no association with PCOS susceptibility
PMID: 41052660
7
CYB5A polymorphism may influence leflunomide treatment response in RA patients
PMID: 37289314
8
No significant association found between CYB5A polymorphism and leflunomide response in RA
PMID: 34160668
Disease Associationsⓘ21
hereditary methemoglobinemiaOpen Targets
0.52Moderate
Abnormality of the skeletal systemOpen Targets
0.41Moderate
46,XY disorder of sex development due to isolated 17,20 lyase deficiencyOpen Targets
0.37Weak
methemoglobinemia due to deficiency of methemoglobin reductaseOpen Targets
0.37Weak
skin woundOpen Targets
0.32Weak
Abnormality of the immune systemOpen Targets
0.31Weak
cholelithiasisOpen Targets
0.29Weak
sinusitisOpen Targets
0.28Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
actinic keratosisOpen Targets
0.06Suggestive
retinal vascular disorderOpen Targets
0.06Suggestive
retinal vascular occlusionOpen Targets
0.06Suggestive
acute myeloid leukemiaOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.03Suggestive
eye injuryOpen Targets
0.02Suggestive
dislocationOpen Targets
0.02Suggestive
obesityOpen Targets
0.02Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.02Suggestive
adenomaOpen Targets
0.02Suggestive
adrenocortical adenomaOpen Targets
0.02Suggestive
Methemoglobinemia and ambiguous genitaliaUniProt
Pathogenic Variants3
NM_148923.4(CYB5A):c.81G>A (p.Trp27Ter)Likely pathogenic
Methemoglobinemia type 4
★☆☆☆2018→ Residue 27
NM_148923.4(CYB5A):c.131A>T (p.His44Leu)Likely pathogenic
Methemoglobinemia type 4
★☆☆☆2018→ Residue 44
NM_148923.4(CYB5A):c.130-2A>GPathogenic
Methemoglobinemia type 4
☆☆☆☆1986
View on ClinVar ↗
Related Genes
MBProtein interaction100%CYB5RLProtein interaction99%CYB5R1Protein interaction99%CYB5R2Protein interaction99%CYCSProtein interaction98%SCDProtein interaction98%
Tissue Expression6 tissues
Liver
100%
Ovary
20%
Lung
17%
Heart
6%
Brain
6%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
CYB5AMBCYB5RLCYB5R1CYB5R2CYCSSCD
PROTEIN STRUCTURE
Preparing viewer…
PDB2I96 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.20LoF Tolerant
pLIⓘ
0.04Tolerant
Observed/Expected LoF0.61 [0.33–1.20]
RankingsWhere CYB5A stands among ~20K protein-coding genes
  • #4,351of 20,598
    Most Researched109 · top quartile
  • #3,980of 5,498
    Most Pathogenic Variants3
  • #12,585of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedCYB5A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Defects in CYB5A and CYB5B impact sterol-C4 oxidation in cholesterol biosynthesis and demonstrate regulatory roles of dimethyl sterols.
PMID: 39489939
Cell Rep · 2024
1.00
2
The association between CYB5A gene rs1790834 polymorphism and clinical improvement after 6 months of leflunomide treatment in women with rheumatoid arthritis.
PMID: 37289314
Clin Rheumatol · 2023
0.90
3
Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with rheumatoid arthritis.
PMID: 34160668
Eur J Clin Pharmacol · 2021
0.80
4
Haplotype-based association of CYB5A gene polymorphisms (rs1790834 and rs1790858) with polycystic ovary syndrome in a south Indian cohort.
PMID: 41052660
Gene · 2025
0.70
5
Effect of mutations in porcine CYB5A and CYP17A1 on the metabolism of pregnenolone.
PMID: 31509771
J Steroid Biochem Mol Biol · 2019
0.60