Seroatlas · Human Serome Atlas

CYB5R3

NADH-cytochrome b5 reductase 3

Also known as: DIA1, NB5R3_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P00387
Gene
CYB5R3
Ensembl
ENSG00000100243
Chromosome
22
Canonical length
301 aa
Protein class
Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Endoplasmic reticulum,Perinuclear theca,Calyx,Connecting piece,Mid piece,Principal piece

OverviewNCBI Gene

This gene encodes cytochrome b5 reductase, which includes a membrane-bound form in somatic cells (anchored in the endoplasmic reticulum, mitochondrial and other membranes) and a soluble form in erythrocytes. The membrane-bound form exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. The membrane-bound form has both membrane-binding and catalytic domains, while the soluble form has only the catalytic domain. Alternate splicing results in multiple transcript variants. Mutations in this gene cause methemoglobinemias. [provided by RefSeq, Jan 2010]

Canonical amino-acid sequenceUniProt

301 residues, UniProt reviewed canonical sequence.

>P00387|CYB5R3
     1  MGAQLSTLGH MVLFPVWFLY SLLMKLFQRS TPAITLESPD IKYPLRLIDR EIISHDTRRF
    61  RFALPSPQHI LGLPVGQHIY LSARIDGNLV VRPYTPISSD DDKGFVDLVI KVYFKDTHPK
   121  FPAGGKMSQY LESMQIGDTI EFRGPSGLLV YQGKGKFAIR PDKKSNPIIR TVKSVGMIAG
   181  GTGITPMLQV IRAIMKDPDD HTVCHLLFAN QTEKDILLRP ELEELRNKHS ARFKLWYTLD
   241  RAPEAWDYGQ GFVNEEMIRD HLPPPEEEPL VLMCGPPPMI QYACLPNLDH VGHPTERCFV
   301  F

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYB5R3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Other membrane
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.29
Highest tissue expression
544 nTPM

Expression across tissuesHPA

Tissue

  • blood vessel: 544 nTPM
  • adipose tissue: 283 nTPM
  • heart muscle: 248 nTPM
  • breast: 193 nTPM
  • endometrium: 185 nTPM
  • seminal vesicle: 183 nTPM

Single-cell type

  • endometrial secretory cells: 109 nCPM
  • ocular epithelial cells: 99 nCPM
  • conjunctival goblet cells: 91 nCPM
  • respiratory secretory cells: 86 nCPM
  • epididymal basal cells: 79 nCPM
  • respiratory basal cells: 76 nCPM

Immune cell

  • eosinophil: 296 nTPM
  • non-classical monocyte: 175 nTPM
  • myeloid DC: 143 nTPM
  • plasmacytoid DC: 141 nTPM
  • intermediate monocyte: 133 nTPM
  • basophil: 117 nTPM

Brain region

  • medulla oblongata: 237 nTPM
  • midbrain: 217 nTPM
  • pons: 208 nTPM
  • hypothalamus: 185 nTPM
  • thalamus: 182 nTPM
  • white matter: 178 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYB5R3.

Disease | AllUniProt

Conditions CYB5R3 is implicated in, by any mechanism.

  • Methemoglobinemia CYB5R3-related (METHB-CYB5R3) MIM:250800

Disease | GeneticClinVar

37 pathogenic / likely-pathogenic of 299 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Deficiency of cytochrome-b5 reductase
  • METHEMOGLOBINEMIA, TYPE II
  • METHEMOGLOBINEMIA, TYPE I
  • CYB5R3-related disorder
  • Hereditary methemoglobinemia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.85
gnomAD pLI
0
gnomAD missense Z
-0.42
DepMap mean gene effect
-0.01
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CYB5R3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CYB5R3 as an antibody target. Whether an autoantibody or antibody against CYB5R3 could matter depends on whether native CYB5R3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CYB5R3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label CYB5R3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/CYB5R3. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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