• Gene id: 3077

Gene Summary

• Gene Symbol: HFE   Gene   UCSC   Ensembl
• Aliases: HFE1, HH, HLA-H, MVCD7, TFQTL2
• Gene name: homeostatic iron regulator
• Alternate names: hereditary hemochromatosis protein, MHC class I-like protein HFE, hereditary hemochromatosis protein HLA-H, high Fe,
• Gene location: 6p22.2 (67756085: 67737374)     Exons: 3     NC_000004.12
• Gene summary(Entrez): 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 th
• OMIM: 613609

Protein Summary

• Protein general information: Q30201  
  • Name: Hereditary hemochromatosis protein (HLA H)
  • Length: 348  
  • Mass: 40,108
• Sequence:

  MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWV
  SSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCP
  DTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRC
  RALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWEPS
  PSGTLVIGVISGIAVFVVILFIGILFIILRKRQGSRGAMGHYVLAERE

• Structural information:
  • Protein Domains: Ig-like (207-298)
  • Interpro: IPR031092  IPR007110  IPR036179  IPR013783  IPR003006   IPR003597  IPR011161  IPR037055  IPR011162  IPR001039  
  • Prosite: PS50835 PS00290
  • PDB: 1A6Z 1C42 1DE4
  • PDBsum: 1A6Z 1C42 1DE4
  • DIP: 2737
  • STRING: ENSP00000417404
• Other Databases: GeneCards:  HFE  Malacards:  HFE

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0002626	negative regulation of T cell antigen processing and presentation	IEA	biological process
GO:0002725	negative regulation of T cell cytokine production	IGI	biological process
GO:0003823	antigen binding	IBA	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005615	extracellular space	IDA	cellular component
GO:0005769	early endosome	IDA	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005887	integral component of plasma membrane	TAS	cellular component
GO:0006461	protein complex assembly	TAS	biological process
GO:0006879	cellular iron ion homeostasis	IEA	biological process
GO:0006953	acute-phase response	IEA	biological process
GO:0006955	immune response	IEA	biological process
GO:0007565	female pregnancy	IEA	biological process
GO:0009897	external side of plasma membrane	IDA	cellular component
GO:0010039	response to iron ion	IMP	biological process
GO:0010106	cellular response to iron ion starvation	IEA	biological process
GO:0010628	positive regulation of gene expression	ISS	biological process
GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation	IDA	biological process
GO:0030509	BMP signaling pathway	IDA	biological process
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0031410	cytoplasmic vesicle	IDA	cellular component
GO:0031410	cytoplasmic vesicle	IDA	cellular component
GO:0032092	positive regulation of protein binding	IGI	biological process
GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IC	biological process
GO:0039706	co-receptor binding	IPI	molecular function
GO:0039706	co-receptor binding	IPI	molecular function
GO:0042446	hormone biosynthetic process	IEA	biological process
GO:0045177	apical part of cell	IDA	cellular component
GO:0045178	basal part of cell	IDA	cellular component
GO:0048260	positive regulation of receptor-mediated endocytosis	IGI	biological process
GO:0048471	perinuclear region of cytoplasm	IDA	cellular component
GO:0048471	perinuclear region of cytoplasm	IDA	cellular component
GO:0055037	recycling endosome	IDA	cellular component
GO:0055072	iron ion homeostasis	IC	biological process
GO:0055072	iron ion homeostasis	IMP	biological process
GO:0060586	multicellular organismal iron ion homeostasis	IEA	biological process
GO:0071281	cellular response to iron ion	IGI	biological process
GO:0090277	positive regulation of peptide hormone secretion	IMP	biological process
GO:0097421	liver regeneration	IEA	biological process
GO:0097459	iron ion import into cell	IDA	biological process
GO:1900121	negative regulation of receptor binding	IDA	biological process
GO:1900122	positive regulation of receptor binding	IGI	biological process
GO:1903991	positive regulation of ferrous iron import into cell	IGI	biological process
GO:1903991	positive regulation of ferrous iron import into cell	IGI	biological process
GO:1904283	negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I	IGI	biological process
GO:1904434	positive regulation of ferrous iron binding	IGI	biological process
GO:1904437	positive regulation of transferrin receptor binding	IGI	biological process
GO:1990357	terminal web	IEA	cellular component
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990641	response to iron ion starvation	IEA	biological process
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:2000008	regulation of protein localization to cell surface	IMP	biological process
GO:2000059	negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process	IDA	biological process
GO:2000272	negative regulation of receptor activity	IDA	biological process
GO:2000273	positive regulation of receptor activity	IGI	biological process
GO:2001186	negative regulation of CD8-positive, alpha-beta T cell activation	IGI	biological process
GO:0002474	antigen processing and presentation of peptide antigen via MHC class I	IKR	biological process
GO:0019882	antigen processing and presentation	IC	biological process
GO:0042605	peptide antigen binding	IKR	molecular function
GO:0042605	peptide antigen binding	IDA	molecular function
GO:0042612	MHC class I protein complex	IKR	cellular component
GO:0042612	MHC class I protein complex	IDA	cellular component
GO:0002626	negative regulation of T cell antigen processing and presentation	IEA	biological process
GO:0002725	negative regulation of T cell cytokine production	IGI	biological process
GO:0003823	antigen binding	IBA	molecular function
GO:0005102	receptor binding	IEA	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005615	extracellular space	IDA	cellular component
GO:0005769	early endosome	IDA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005887	integral component of plasma membrane	TAS	cellular component
GO:0006461	protein complex assembly	TAS	biological process
GO:0006810	transport	IEA	biological process
GO:0006811	ion transport	IEA	biological process
GO:0006879	cellular iron ion homeostasis	IEA	biological process
GO:0006879	cellular iron ion homeostasis	TAS	biological process
GO:0006953	acute-phase response	IEA	biological process
GO:0006955	immune response	IEA	biological process
GO:0007565	female pregnancy	IEA	biological process
GO:0009897	external side of plasma membrane	IDA	cellular component
GO:0010039	response to iron ion	IMP	biological process
GO:0010106	cellular response to iron ion starvation	IEA	biological process
GO:0010628	positive regulation of gene expression	IEA	biological process
GO:0010628	positive regulation of gene expression	ISS	biological process
GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation	IDA	biological process
GO:0016020	membrane	IEA	cellular component
GO:0016021	integral component of membrane	IEA	cellular component
GO:0030509	BMP signaling pathway	IDA	biological process
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0031410	cytoplasmic vesicle	IDA	cellular component
GO:0031410	cytoplasmic vesicle	IDA	cellular component
GO:0032092	positive regulation of protein binding	IGI	biological process
GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IC	biological process
GO:0039706	co-receptor binding	IPI	molecular function
GO:0039706	co-receptor binding	IPI	molecular function
GO:0042446	hormone biosynthetic process	IEA	biological process
GO:0045177	apical part of cell	IEA	cellular component
GO:0045177	apical part of cell	IDA	cellular component
GO:0045178	basal part of cell	IDA	cellular component
GO:0048260	positive regulation of receptor-mediated endocytosis	IGI	biological process
GO:0048471	perinuclear region of cytoplasm	IDA	cellular component
GO:0048471	perinuclear region of cytoplasm	IDA	cellular component
GO:0055037	recycling endosome	IDA	cellular component
GO:0055072	iron ion homeostasis	IEA	biological process
GO:0055072	iron ion homeostasis	IEA	biological process
GO:0055072	iron ion homeostasis	IC	biological process
GO:0055072	iron ion homeostasis	IMP	biological process
GO:0060586	multicellular organismal iron ion homeostasis	IEA	biological process
GO:0071281	cellular response to iron ion	IGI	biological process
GO:0090277	positive regulation of peptide hormone secretion	IMP	biological process
GO:0097421	liver regeneration	IEA	biological process
GO:0097459	iron ion import into cell	IEA	biological process
GO:0097459	iron ion import into cell	IEA	biological process
GO:0097459	iron ion import into cell	IDA	biological process
GO:1900121	negative regulation of receptor binding	IDA	biological process
GO:1900122	positive regulation of receptor binding	IGI	biological process
GO:1903991	positive regulation of ferrous iron import into cell	IGI	biological process
GO:1903991	positive regulation of ferrous iron import into cell	IGI	biological process
GO:1904283	negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I	IGI	biological process
GO:1904434	positive regulation of ferrous iron binding	IGI	biological process
GO:1904437	positive regulation of transferrin receptor binding	IGI	biological process
GO:1990357	terminal web	IEA	cellular component
GO:1990459	transferrin receptor binding	IEA	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990641	response to iron ion starvation	IEA	biological process
GO:1990712	HFE-transferrin receptor complex	IEA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:2000008	regulation of protein localization to cell surface	IMP	biological process
GO:2000059	negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process	IDA	biological process
GO:2000272	negative regulation of receptor activity	IDA	biological process
GO:2000273	positive regulation of receptor activity	IGI	biological process
GO:2001186	negative regulation of CD8-positive, alpha-beta T cell activation	IGI	biological process
GO:0002474	antigen processing and presentation of peptide antigen via MHC class I	IKR	biological process
GO:0019882	antigen processing and presentation	IC	biological process
GO:0042605	peptide antigen binding	IKR	molecular function
GO:0042605	peptide antigen binding	IDA	molecular function
GO:0042612	MHC class I protein complex	IKR	cellular component
GO:0042612	MHC class I protein complex	IDA	cellular component
GO:0002725	negative regulation of T cell cytokine production	IGI	biological process
GO:0003823	antigen binding	IBA	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005615	extracellular space	IDA	cellular component
GO:0005769	early endosome	IDA	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005887	integral component of plasma membrane	TAS	cellular component
GO:0006461	protein complex assembly	TAS	biological process
GO:0006879	cellular iron ion homeostasis	TAS	biological process
GO:0009897	external side of plasma membrane	IDA	cellular component
GO:0010039	response to iron ion	IMP	biological process
GO:0010628	positive regulation of gene expression	ISS	biological process
GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation	IDA	biological process
GO:0030509	BMP signaling pathway	IDA	biological process
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0030881	beta-2-microglobulin binding	IPI	molecular function
GO:0031410	cytoplasmic vesicle	IDA	cellular component
GO:0031410	cytoplasmic vesicle	IDA	cellular component
GO:0032092	positive regulation of protein binding	IGI	biological process
GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IC	biological process
GO:0039706	co-receptor binding	IPI	molecular function
GO:0039706	co-receptor binding	IPI	molecular function
GO:0045177	apical part of cell	IDA	cellular component
GO:0045178	basal part of cell	IDA	cellular component
GO:0048260	positive regulation of receptor-mediated endocytosis	IGI	biological process
GO:0048471	perinuclear region of cytoplasm	IDA	cellular component
GO:0048471	perinuclear region of cytoplasm	IDA	cellular component
GO:0055037	recycling endosome	IDA	cellular component
GO:0055072	iron ion homeostasis	IC	biological process
GO:0055072	iron ion homeostasis	IMP	biological process
GO:0071281	cellular response to iron ion	IGI	biological process
GO:0090277	positive regulation of peptide hormone secretion	IMP	biological process
GO:0097459	iron ion import into cell	IDA	biological process
GO:1900121	negative regulation of receptor binding	IDA	biological process
GO:1900122	positive regulation of receptor binding	IGI	biological process
GO:1903991	positive regulation of ferrous iron import into cell	IGI	biological process
GO:1903991	positive regulation of ferrous iron import into cell	IGI	biological process
GO:1904283	negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I	IGI	biological process
GO:1904434	positive regulation of ferrous iron binding	IGI	biological process
GO:1904437	positive regulation of transferrin receptor binding	IGI	biological process
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990459	transferrin receptor binding	IPI	molecular function
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:1990712	HFE-transferrin receptor complex	IDA	cellular component
GO:2000008	regulation of protein localization to cell surface	IMP	biological process
GO:2000059	negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process	IDA	biological process
GO:2000272	negative regulation of receptor activity	IDA	biological process
GO:2000273	positive regulation of receptor activity	IGI	biological process
GO:2001186	negative regulation of CD8-positive, alpha-beta T cell activation	IGI	biological process
GO:0002474	antigen processing and presentation of peptide antigen via MHC class I	IKR	biological process
GO:0019882	antigen processing and presentation	IC	biological process
GO:0042605	peptide antigen binding	IKR	molecular function
GO:0042605	peptide antigen binding	IDA	molecular function
GO:0042612	MHC class I protein complex	IKR	cellular component
GO:0042612	MHC class I protein complex	IDA	cellular component

Diseases

Associated diseases	References
Cancer	GAD: 16216474
Cancer (Adenocarcinoma)	GAD: 18470614
Cancer (Adenoma)	GAD: 15956653
Cancer (Hepatocellular)	GAD: 11096344
Cancer (bladder)	GAD: 19692168
Cancer (cervical)	GAD: 16414021
Cancer (colon)	GAD: 12529348
Cancer (colorectal)	GAD: 12433710
Cancer (leukemia)	GAD: 19806355
Cancer (liver)	GAD: 16174459
Cancer (lung)	GAD: 18676680
Cancer (myeloma)	GAD: 17001480
Cancer (non-melanoma skin cancer)	GAD: 15914210
Cancer (prostate)	GAD: 16003728
Colon cancer	GAD: 12529348
Cancer (breast)	GAD: 15894659
Apoplexy	GAD: 12364722
Atherosclerosis	GAD: 9753040
Hypertension	GAD: 19862010
Cardiovascular disease	GAD: 12514663
Cardiovascular disease	GAD: 12514663
Peripheral vascular disease	GAD: 20927387
Thromboembolism	GAD: 10520044
Venous thromboembolism	GAD: 10233369
Juvenile hemochromatosis	GAD: 12064925
Hemochromatosis	OMIM: 613609
Gaucher disease	GAD: 20575041
Cystic fibrosis	GAD: 10464603
Gastrointestinal hemorrhage	GAD: 18460494
Liver disease	GAD: 18820912
Liver disease	GAD: 14675248
Hyperthyroidism	GAD: 18651828
Macular degeneration	GAD: 19852572
Alpha-thalassemia	GAD: 17160266
Anemia	GAD: 18657084
Beta-thalassemia	GAD: 11869934
Aplastic anemia	GAD: 19731820
Hematologic diseases	GAD: 11836162
Thrombophilia	GAD: 14706682
Arthritis	GAD: 11981324
Rheumatoid arthritis	GAD: 15785438
Multiple sclerosis	GAD: 18675463
Celiac disease	GAD: 12145797
Fatty liver	GAD: 20216079
Porphyria	GAD: 17137171
Hypertriglyceridemia	GAD: 19820015
Obesity	GAD: 19884647
Porphyria	OMIM: 613609
Porphyria	OMIM: 613609
Diabetic retinopathy	GAD: 14618419
Diabetes	GAD: 12601293
Insulin resistance	GAD: 14752836
Osteoarthritis	GAD: 19264516
Degenerative arthropathy	GAD: 16583477
Neurodegenerative diseases	GAD: 20164577
Amyotrophic lateral sclerosis (ALS)	GAD: 18689356
Parkinson disease	GAD: 12902032
Alzheimer's disease	OMIM: 613609
Cirrhosis	GAD: 16157826
Decreased libido	MIK: 11153416
Chronic renal failure	GAD: 16138214
Kidney diseases	GAD: 18025780
Abortion	GAD: 20587610
Recurrent pregnancy loss (RPL)	GAD: 15304010
Polycystic ovary syndrome (PCOS)	INFBASE: 21701160
Abnormal sperm motility	MIK: 18846434
Male factor infertility	MIK: 22504868
Male factor infertility	MIK: 18395717
Male factor infertility	MIK: 18395717
Erectile dysfunction	MIK: 11153416
Hypogonadotropic hypogonadism	MIK: 16988327
Chronic obstructive pulmonary disease (COPD)	GAD: 19625176
Varicose ulcer	GAD: 19958990
Alpha 1-antitrypsin deficiency	GAD: 20208481
Arthralgia	GAD: 18403938
Calcinosis	GAD: 12117686
Hepatic iron and fibrosis	GAD: 12085358
Microvascular complications of diabetes	OMIM: 613609
Genital diseases	GAD: 19799358
Abnormal sperm motility	MIK: 18846434
Decreased libido, erectile dysfunction	MIK: 11153416
Hypogonadism	MIK: 16988327
Male infertility	MIK: 17067586

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
22504868	Idiopathic male infertility	HFE (C282Y, H63D and S65C)	Chinese Han	867 (444 infertile men (including 169 with idiopathic azoospermia), 423 controls with proven fertility)	Male infertility, Female infertility
18846434	Abnormal sperm motility			148 infertile men	Male infertility
18395717	Male infertility			315 (127 infertile men (including 97 with idiopathic infertility), 188 controls)	Male infertility	HFE TF
16988327	Hypogonadism, reduced bone mineral density, hemochromatosis				Male infertility, Female infertility
17067586	Male infertility	C282Y, H63D		462 (262 infertile men, 200 fertile men)	Male infertility, Female infertility
11153416	Decreased libido, erectile dysfunction				Male infertility