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FLASH GENE

Symbol

HFE

contributors: mct - updated : 24-10-2011

HGNC name	hemochromatosis
HGNC id	4886

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HFE hemochromatosis VGP porphyria variegata
Location	6p21.3      Physical location : 26.087.508 - 26.095.469
Synonym symbol(s)	HLA-H, HH, HFE1

DNA

TYPE	functioning gene
SPECIAL FEATURE	gene in gene, antisens
text	HFE antisense RNA partially covers HFE mRNA
STRUCTURE	7.96 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	likely several other transcripts

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000410 6 splicing 2222 variant 1 40.11 348 - 2001 11532995 containing exon 2a (longer than 2b) containing exon 3a (longer than 3b) containing exon 4a (longer than 4b & 4c) containing exon 6a (longer than 6b) laking exon 7 encoding for the longest product variant 2 4 splicing 878 variant 2 18.52 161 - 2001 11532995 containing exon 2a (longer than 2b) containing exon 3b (shorter than 3a) containing exon 7b (shorter than 7a) laking exons 4, 5 & 6 NM_139003 5 splicing 1904 variant 3 27.58 242 - 2001 11532995 containing exon 2a (longer than 2b) containing exon 4b containing exon 6a (longer than 6b) laking exons 3 & 7 NM_139004 5 splicing 1946 variant 4 29.06 256 - 2001 11532995 containing exon 2a (longer than 2b) containing exon 4a (longer than 4b & 4c) containing exon 6a (longer than 6b) laking exons 3 & 7 variant 5 5 splicing 1417 variant 5 32.05 276 - 2001 11532995 containing exon 2a (longer than 2b) containing exon 3a (longer than 3b) containing exon 4c (shorter than 4a & 4b) containing exon 7a (longer than 7b) laking exons 5 & 6 NM_139006 6 splicing 2180 variant 6 38.49 334 - 2001 11532995 containing exon 2a (longer than 2b) containing exon 3a (longer than 3b) containing exon 4b containing exon 6b (shorter than 6a) laking exon 7 NM_139007 5 splicing 1958 variant 7 29.5 260 - 2001 11532995 containing exon 3a (longer than 3b) containing exon 4a (longer than 4b & 4c) containing exon 6a (longer than 6b) laking exons 2 & 7 NM_139008 5 splicing 1916 variant 8 28.02 246 - 2001 11532995 a 5 exons variant containing exon 3a (longer than 3b) containing exon 4b containing exon 6a (longer than 6b) laking exons 2 & 7 NM_139009 6 splicing 2153 variant 9 37.38 325 - 2001 11532995 containing exon 2b (shorter than 2a) containing exon 3a (longer than 3b) containing exon 4a (longer than 4b & 4c) containing exon 6a (longer than 6b) laking exon 7 NM_139010 4 splicing 1682 variant 10 18.6 168 - 2001 11532995 a 4 exons variant containing exon 4a (longer than 4b & 4c) containing exon 6a (longer than 6b) laking exons 2, 3 & 7 NM_139011 3 splicing 1406 variant 11 8.08 76 - 2001 11532995 containing exon 6a (longer than 6b) laking exons 2, 3, 4, & 7 encoding for the shortest product

EXPRESSION

Type

widely

constitutive of

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine duodenum   moderately Endocrine adrenal gland       highly Lymphoid/Immune spleen       predominantly Nervous brain       moderately Reproductive female system breast mammary gland   highly   female system uterus cervix   moderately   male system prostate     highly   male system testis     lowly Respiratory lung       moderately Skin/Tegument skin       lowly Urinary bladder       highly   kidney       highly Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic       highly Connective       moderately Epithelial barrier lining retinal pigment epithelium (RPE)   moderately

cells

System Cell Pubmed Species Stage Rna symbol Digestive enterocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an immunoglobulin-like C1-type domain
	a class I histocompatibility antigen domain

HOMOLOGY

interspecies	homolog to murine Hfe (69.36 pc)
	homolog to rattus Hfe (69.25 pc)

Homologene

FAMILY

MHC class I family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
text	associated with TFRC in crypt cells

basic FUNCTION	soluble form (regulating cellular iron transport) and a non soluble form (involved in iron deficiency)
	influencing serum transferrin saturation in heterozygotes C282Y or H63D
	influences the functional properties of TFR2, suggesting a model in which the interaction of these proteins might influence signal transduction to hepcidin)
	TFR2/HFE complex is required for transcriptional regulation of hepcidin by holo-TF
	both HFE and TFR2 are necessary for regulation of hepcidin (HAMP) expression
	TFR2 and HFE are involved in holotransferrin-dependent signaling for the regulation of FURIN which involved Erk phosphorylation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

metal

signaling

iron

a component	negative modulator of the uptake of transferrin-bound iron from plasma
	complexing with beta 2 microglobulin and transferrin receptor (TFRC)

INTERACTION

DNA

RNA

small molecule

protein

transferrin receptor (TFRC)

cell & other

REGULATION

inhibited by

HFE protein expression is negatively regulated by the antisense transcript in vitro

ASSOCIATED DISORDERS

corresponding disease(s)

HFE , VGP

Susceptibility

Variant & Polymorphism SNP	HFE C282Y and H63D polymorphism inducing a variation in iron status: serum transferin saturation is more affected than is serum ferritin.

Candidate gene	for amyotrophic lateral sclerosis
Marker
Therapy target

ANIMAL & CELL MODELS

	knock-out Hfe -/- mice
	iron overload due to deletion of Tfr2 in mice is more severe than that due to Hfe, and loss of both molecules results in pronounced iron overload