HFE

Protein identityUniProt · HPA

UniProt accession

Q30201

Gene

HFE

Ensembl

ENSG00000010704

Chromosome

6

Canonical length

348 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins

Subcellular location

Nucleoplasm,Plasma membrane

OverviewNCBI Gene

The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene. [provided by RefSeq, May 2022]

Canonical amino-acid sequenceUniProt

348 residues, UniProt reviewed canonical sequence.

>Q30201|HFE
     1  MGPRARPALL LLMLLQTAVL QGRLLRSHSL HYLFMGASEQ DLGLSLFEAL GYVDDQLFVF
    61  YDHESRRVEP RTPWVSSRIS SQMWLQLSQS LKGWDHMFTV DFWTIMENHN HSKESHTLQV
   121  ILGCEMQEDN STEGYWKYGY DGQDHLEFCP DTLDWRAAEP RAWPTKLEWE RHKIRARQNR
   181  AYLERDCPAQ LQQLLELGRG VLDQQVPPLV KVTHHVTSSV TTLRCRALNY YPQNITMKWL
   241  KDKQPMDAKE FEPKDVLPNG DGTYQGWITL AVPPGEEQRY TCQVEHPGLD QPLIVIWEPS
   301  PSGTLVIGVI SGIAVFVVIL FIGILFIILR KRQGSRGAMG HYVLAERE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HFE 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

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

15 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HFE.

Disease | AllUniProt

Conditions HFE is implicated in, by any mechanism.

• Hemochromatosis 1 (HFE1) MIM:235200

Disease | GeneticClinVar

44 pathogenic / likely-pathogenic of 334 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary hemochromatosis
• Hemochromatosis type 1
• 6 conditions
• Juvenile hemochromatosis
• Hereditary cancer-predisposing syndrome

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)

1.19

gnomAD pLI

0

gnomAD missense Z

0.63

DepMap mean gene effect

0.09

DepMap dependency class

none

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

• BMP signaling pathway
• cell surface receptor signaling pathway
• cellular response to iron ion
• gene expression
• hormone biosynthetic process
• intracellular iron ion homeostasis
• multicellular organismal-level iron ion homeostasis
• negative regulation of CD8-positive, alpha-beta T cell activation
• negative regulation of proteasomal ubiquitin-dependent protein catabolic process
• negative regulation of T cell cytokine production
• negative regulation of ubiquitin-dependent protein catabolic process
• positive regulation of gene expression
• positive regulation of peptide hormone secretion
• positive regulation of receptor-mediated endocytosis
• positive regulation of SMAD protein signal transduction
• protein-containing complex assembly
• receptor-mediated endocytosis
• regulation of iron ion transport
• regulation of protein localization to cell surface
• response to iron ion
• response to iron ion starvation
• transferrin transport
• urate metabolic process
• negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I

Molecular functions

• beta-2-microglobulin binding
• co-receptor binding
• signaling receptor binding
• transferrin receptor binding
• transporter activator activity

Cellular components

• apical part of cell
• basal part of cell
• cytoplasmic vesicle
• early endosome
• external side of plasma membrane
• extracellular space
• HFE-transferrin receptor complex
• nucleoplasm
• perinuclear region of cytoplasm
• plasma membrane
• recycling endosome

Protein domainsUniProt · Pfam · InterPro

• MHC class I alpha chain, alpha1 alpha2 domains
• Immunoglobulin/major histocompatibility complex, conserved site
• Immunoglobulin C1-set
• Immunoglobulin-like domain
• MHC class I-like antigen recognition-like
• MHC classes I/II-like antigen recognition protein
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• MHC class I-like antigen recognition-like superfamily
• Antigen-presenting and immune regulatory MHC class I-related
• Class I Histocompatibility antigen, domains alpha 1 and 2
• Immunoglobulin C1-set domain

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Ion transport
• Iron
• Iron transport
• Membrane
• Signal
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

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

• B2M
• TFRC