HFE hemochromatosis [Homo sapiens] - Gene

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Summary

Official Symbol: HFEprovided by HGNC
Official Full Name: hemochromatosisprovided by HGNC
Primary source: HGNC:4886
See related: Ensembl:ENSG00000010704; HPRD:01993; MIM:613609; Vega:OTTHUMG00000016348
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HH; HFE1; HLA-H; MVCD7; TFQTL2; MGC103790; MGC:150812; dJ221C16.10.1; IMAGE:40125754
Summary: 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. At least nine alternatively spliced variants have been described for this gene. Additional variants have been found but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 6p21.3

Sequence :: Chromosome: 6; NC_000006.11 (26087509..26095469)

See HFE in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Mutant His63Asp HFE increases tau phosphorylation via glycogen synthase kinase (GSK)-3beta activity and iron-mediated oxidative stress.
Title: Expression of the HFE allelic variant H63D in SH-SY5Y cells affects tau phosphorylation at serine residues.
Results describe the prevalence of C282Y (c.845 G>A), H63D (c.187 C>G), and S65C (c.193A>T) alleles of HFE gene in the Lithuanian population.
Title: Prevalence of C282Y, H63D, and S65C mutations in hereditary HFE-hemochromatosis gene in Lithuanian population.
in cardiac asymptomatic subjects with HH with C282Y homozygosity, known to be the most common HFE gene mutation to cause HH.
Title: Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.
No significant differences are found in genotype and allele frequencies between Parkinson's disease patients and controls for the HFE polymorphisms studied.
Title: Association study between four polymorphisms in the HFE, TF and TFR genes and Parkinson's disease in southern Italy.
Contrary to previous reports of HFE gene polymorphisms in Wilson disease patients, in our cohort the allele frequencies were in line with frequencies obtained for general population.
Title: Iron metabolism and the role of HFE gene polymorphisms in Wilson disease.
genetic variations in the HFE gene, but not plasma ferritin may have a role in coronary heart disease in Chinese
Title: Plasma ferritin levels, genetic variations in HFE gene, and coronary heart disease in Chinese: a case-control study.
The HFE H63D mutation carrier frequency in healthy Lebanese is comparable to other populations in the region, and it does not result in significant biochemical iron overload.
Title: Should we screen for hereditary hemochromatosis in healthy Lebanese: a pilot study.
HFE rs1800562 C282Y variant exerts a direct pleiotropic effect on the iron parameters, in part independent of hepcidin.
Title: Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations.
Our systematic review does not support an association between the HFE genetic variants (C282Y and H63D)and the presence of nonalcoholic fatty liver disease.
Title: Hemochromatosis gene and nonalcoholic fatty liver disease: a systematic review and meta-analysis.
Although HFE mutations produce initially elevated haemoglobin & iron stores, there is no effect on their rate of decline when individuals are subjected to haemoglobin & iron loss with repeated blood donation.
Title: The impact of HFE mutations on haemoglobin and iron status in individuals experiencing repeated iron loss through blood donation*.

Submit: New GeneRIF Correction See all (339)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

A genome-wide association study of red blood cell traits using the electronic medical record.

A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.

Alzheimer disease, susceptibility to

MIM: 104300

Common variants at 10 genomic loci influence hemoglobin A ??(C) levels via glycemic and nonglycemic pathways.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume.

Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.

Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.

Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.

Microvascular complications of diabetes 7

MIM: 612635

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.

Porphyria cutanea tarda, susceptibility to

MIM: 176100

Porphyria variegata, susceptibility to

MIM: 176200

Sequence variants in three loci influence monocyte counts and erythrocyte volume.

Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels.

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Myristoylation of HIV-1 Nef at position 2 and the PxxP proline-rich motif of Nef at positions 62-65 are required for Nef-induced downregulation of HFE; amino acid residue Y282 in HFE is involved in the downregulation by Nef	PubMed
	nef	HIV-1 Nef downregulates the macrophage-expressed MHC 1b protein HFE by rerouting HFE to a perinuclear structure that overlaps the trans-Golgi network, causing a 90% reduction of surface HFE	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
Q30201	P61769	B2M	HPRD	PubMed
Q30201	Q9UP52	TFR2	HPRD	PubMed
Q30201	P02786	TFRC	HPRD	PubMed
BioGRID:109325	BioGRID:124085	SYVN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109325	BioGRID:112894	TFR2	BioGRID	PubMed	Co-crystal Structure
BioGRID:109325	BioGRID:112895	TFRC	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:109325	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
antigen processing and presentation	IEA Inferred from Electronic Annotation more info
antigen processing and presentation of peptide antigen via MHC class I	IEA Inferred from Electronic Annotation more info
cellular iron ion homeostasis	TAS Traceable Author Statement more info	PubMed
cellular response to iron ion starvation	IEA Inferred from Electronic Annotation more info
female pregnancy	IEA Inferred from Electronic Annotation more info
hormone biosynthetic process	IEA Inferred from Electronic Annotation more info
immune response	IEA Inferred from Electronic Annotation more info
ion transport	IEA Inferred from Electronic Annotation more info
iron ion transport	TAS Traceable Author Statement more info	PubMed
multicellular organismal iron ion homeostasis	IEA Inferred from Electronic Annotation more info
protein complex assembly	TAS Traceable Author Statement more info	PubMed
receptor-mediated endocytosis	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
MHC class I protein complex	IEA Inferred from Electronic Annotation more info
apical part of cell	IDA Inferred from Direct Assay more info	PubMed
basal part of cell	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	TAS Traceable Author Statement more info	PubMed
cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
early endosome	IDA Inferred from Direct Assay more info	PubMed
integral to membrane	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info	PubMed
recycling endosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: hereditary hemochromatosis protein

Names: hereditary hemochromatosis protein; high Fe; MHC class I-like protein HFE; hereditary hemochromatosis protein HLA-H

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008720.1 RefSeqGene

Range

5001..12961

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000410.3 → NP_000401.1 hereditary hemochromatosis protein isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform.

Source sequence(s)

AF115265, AJ249337, U91328

Consensus CDS

CCDS4578.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000417404, OTTHUMP00000215786, ENST00000357618, OTTHUMT00000356133

Conserved Domains (2) summary

cd07698
Location:223 – 298
Blast Score: 265

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00129
Location:27 – 202
Blast Score: 333

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_139003.2 → NP_620572.1 hereditary hemochromatosis protein isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 3).

Source sequence(s)

AF149804, AJ249335, U91328

Consensus CDS

CCDS47386.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000337819, OTTHUMP00000215793, ENST00000336625, OTTHUMT00000356143

Conserved Domains (2) summary

cd07698
Location:110 – 192
Blast Score: 273

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00129
Location:27 – 113
Blast Score: 131

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_139004.2 → NP_620573.1 hereditary hemochromatosis protein isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an internal in-frame segment of the coding region, compared to variant 1, resulting in a shorter protein (isoform 4).

Source sequence(s)

AJ249337, U91328

Consensus CDS

CCDS4579.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000313776, OTTHUMP00000215790, ENST00000317896, OTTHUMT00000356137

Conserved Domains (2) summary

cd07698
Location:131 – 206
Blast Score: 266

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00129
Location:27 – 113
Blast Score: 131

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_139006.2 → NP_620575.1 hereditary hemochromatosis protein isoform 6 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 6).

Source sequence(s)

AF079407, AJ249335, U91328

Consensus CDS

CCDS54974.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000420802, OTTHUMP00000215816, ENST00000461397, OTTHUMT00000356202

Conserved Domains (2) summary

cd07698
Location:207 – 284
Blast Score: 271

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00129
Location:27 – 202
Blast Score: 332

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_139007.2 → NP_620576.1 hereditary hemochromatosis protein isoform 7 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (7) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein isoform (7).

Source sequence(s)

AJ249336, U91328

Consensus CDS

CCDS4580.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000259699, OTTHUMP00000215788, ENST00000349999, OTTHUMT00000356135

Conserved Domains (2) summary

cd07698
Location:135 – 210
Blast Score: 266

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00129
Location:27 – 114
Blast Score: 218

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_139008.2 → NP_620577.1 hereditary hemochromatosis protein isoform 8 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (8) lacks two internal in-frame segments of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 8).

Source sequence(s)

AF079409, AJ249335, U91328

Consensus CDS

CCDS54975.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000420559, OTTHUMP00000215817, ENST00000488199, OTTHUMT00000356203

Conserved Domains (2) summary

cd07698
Location:119 – 196
Blast Score: 272

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00129
Location:27 – 114
Blast Score: 217

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_139009.2 → NP_620578.1 hereditary hemochromatosis protein isoform 9 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (9) lacks an internal in-frame segment of the coding region through the use of an alternate splice acceptor site, as compared to variant 1, resulting in a shorter protein (isoform 9).

Source sequence(s)

AJ249335, U91328

Consensus CDS

CCDS47387.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000380217, OTTHUMP00000215789, ENST00000397022, OTTHUMT00000356136

Conserved Domains (2) summary

cd07698
Location:200 – 275
Blast Score: 263

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00129
Location:23 – 179
Blast Score: 296

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_139010.2 → NP_620579.1 hereditary hemochromatosis protein isoform 10 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (10) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 10).

Source sequence(s)

AJ250635, U91328

Consensus CDS

CCDS4581.1

UniProtKB/Swiss-Prot

Q30201

Related

ENSP00000312342, OTTHUMP00000215791, ENST00000353147, OTTHUMT00000356138

Conserved Domains (1) summary

cd07698
Location:43 – 118
Blast Score: 269

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
NM_139011.2 → NP_620580.1 hereditary hemochromatosis protein isoform 11 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (11) lacks a large internal part of the coding region but the reading frame is maintained, as compared to variant 1. The protein encoded is the shortest isoform (11).

Source sequence(s)

AJ249338, U91328

Consensus CDS

CCDS4582.1

Related

ENSP00000315936, OTTHUMP00000215787, ENST00000352392, OTTHUMT00000356134

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p5 Primary Assembly

Range

26087509..26095469

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

26030572..26038529

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_139002.2: Suppressed sequence

Description

NM_139002.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NM_139005.2: Suppressed sequence

Description

NM_139005.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF184234.1	AAF01222.1
genomic	AF204869.1	None
genomic	AF331065.1	AAK16502.1
genomic	AF525359.1	AAM82608.1
genomic	AF525499.1	AAM91950.1
genomic	CH471087.1	EAW55516.1
		EAW55517.1
		EAW55518.1
		EAW55519.1
		EAW55520.1
		EAW55521.1
		EAW55522.1
		EAW55523.1
		EAW55524.1
		EAW55525.1
		EAW55526.1
		EAW55527.1
genomic	CS187189.1	CAJ42862.1
genomic	EU523119.1	ACB21042.1
genomic	U80914.1	AAD00449.1
genomic	U91328.1	AAB82083.1
genomic	Y09801.1	CAA70934.1
genomic	Z92910.1	CAB07442.1
mRNA	AF079407.1	AAC62646.1
mRNA	AF079408.1	AAC62647.1
mRNA	AF079409.1	AAC62648.1
mRNA	AF109385.1	AAD52104.1
mRNA	AF115264.1	AAG29571.1
mRNA	AF115265.1	AAG29572.1
mRNA	AF144238.1	AAG29573.1
mRNA	AF144239.1	AAG29574.1
mRNA	AF144240.1	AAG29575.1
mRNA	AF144241.1	AAG29576.1
mRNA	AF144242.1	AAG29577.1
mRNA	AF144243.1	AAG29578.1
mRNA	AF144244.1	AAG29579.1
mRNA	AF144245.1	AAG29580.1
mRNA	AF147392.1	None
mRNA	AF149804.1	AAG29342.1
mRNA	AF150664.1	AAG29343.1
mRNA	AJ249335.1	CAC67792.1
mRNA	AJ249336.1	CAC67793.1
mRNA	AJ249337.1	CAC67794.1
mRNA	AJ249338.1	CAC67795.1
mRNA	AJ250635.1	CAC80805.1
mRNA	AJ298839.1	None
mRNA	AJ298840.1	None
mRNA	AJ404378.1	None
mRNA	AK293393.1	BAG56902.1
mRNA	AK300933.1	BAG62562.1
mRNA	AK316502.1	BAH14873.1
mRNA	AY205604.1	AAO47091.1
mRNA	BC074721.2	AAH74721.1
mRNA	BC117201.1	AAI17202.1
mRNA	BC117203.1	AAI17204.1
mRNA	BC143887.1	None
mRNA	JN375752.1	AEO50365.1
mRNA	JN375753.1	AEO50366.1
mRNA	JN375754.1	AEO50367.1
mRNA	JN375755.1	AEO50368.1
mRNA	JN375756.1	AEO50369.1
mRNA	JN375757.1	AEO50370.1
mRNA	JN375758.1	AEO50371.1
mRNA	JN375759.1	AEO50372.1
mRNA	U60319.1	AAC51823.1
other-genetic	HQ258197.1	ADR82951.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q30201.1	GenPept	UniProtKB/Swiss-Prot:Q30201
Q6B0J5	GenPept	UniProtKB/TrEMBL:Q6B0J5
Q86WL1	GenPept	UniProtKB/TrEMBL:Q86WL1
Q8MH46	GenPept	UniProtKB/TrEMBL:Q8MH46
Q9BXI5	GenPept	UniProtKB/TrEMBL:Q9BXI5
Q9HC63	GenPept	UniProtKB/TrEMBL:Q9HC63
Q9HC65	GenPept	UniProtKB/TrEMBL:Q9HC65
Q9HC66	GenPept	UniProtKB/TrEMBL:Q9HC66
Q9HC67	GenPept	UniProtKB/TrEMBL:Q9HC67
Q9HC69	GenPept	UniProtKB/TrEMBL:Q9HC69
Q9HC71	GenPept	UniProtKB/TrEMBL:Q9HC71
Q9HC72	GenPept	UniProtKB/TrEMBL:Q9HC72
Q9TQ79	GenPept	UniProtKB/TrEMBL:Q9TQ79
Q9UK37	GenPept	UniProtKB/TrEMBL:Q9UK37
Q9UM46	GenPept	UniProtKB/TrEMBL:Q9UM46