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HFE
'Hereditary Hemochromatosis Gene'
Gene ID: 3077; Protein ID: Q30201
M.Tevfik DORAK, MD PhD
rs1800562 (C282Y) risk associations with cancer:
Childhood leukemia: Dorak, 1999 & Davis & Dorak, 2010
Breast cancer: Kallianpur, 2004 & Osborne, 2010
Colorectal cancer: Shaheen, 2003 & Osborne, 2010
Various cancers: Beckman, 1999
rs1800562 (C282Y) risk associations in GWAS:
Total & LDL cholesterol (decrease): Teslovich, 2010 (see Fig 1)
Cardiovascular disease risk factors (decrease in LDL, increase in ferritin): Middelberg, 2011 (see Table S4)
Glycated hemoglobin (HbA1c) levels (increase): Soranzo, 2010
Various iron status parameters:
Benyamin, 2008; Benyamin, 2009; Ganesh, 2009; Kullo, 2010; Soranzo, 2011; McLaren, 2011; Kutalik, 2011; Traglia, 2011
Curious associations of intron 1 SNP rs9366637 allele T:
High birth weight (Dorak, 2009; suppl info); protection from coronary heart disease (Shi, 2011)
Chromosome 6p21.3 location 26,195,427 - 26,205,046
Entrez Gene OMIM NCBI BookShelf
NCBI Map Viewer (HFE) NCBI Map Viewer (HFE & Histon Clusters)
dbSNP (all SNPs) dbSNP (cSNPs only) Map Viewer Variation View (all SNPs)
Investigating the genetic basis of iron overload: Flash Tutorial on HFE Variation (click RUN)
Ensembl (isoform 16348) Vega Ensembl Map GeneAtlas UCSC Browser
SNP@Ethnos: HFE Diseasome: HFE MutDB: HFE
Atlas of Genetics & Cytogenetics in Oncology & Hematology: HFE TFRC
Genetic Association Database: Gene View & Disease View
Human Genetic Mutations Database
Reference Sequences: Genomic mRNA Protein
GeneCards GeneNote UniGene GDB iHOP T1D T2D Dept of Energy EC Gene
UniProt / SwissProt Structure 1 Structure 2 HomoloGene HPRD AceView
Expression Profiles: HFE TFRC HAMP SLC11A2 SLC40A1
PubMed Search Google Search Medline Plus
Hereditary Hemochromatosis:
Genes and Disease Gene Reviews CDC NHGRI Iron Disorders Institute Wellcome Trust
Comparative Toxicogenomic Database: Iron
Comparative Toxicogenomic Database: HFE; TFRC; HAMP; DMT1
NIH Genetic Association Database Search: HFE HAMP TFRC
NIH Genetic Association Database HFE Gene Expert: ID 710
Functional Analysis of SNPs:
ABI TaqMan Assays for HFE Region SNPs
Affymetrix 500K GeneChip Array Coverage of the HFE Gene:
rs16891264 (15kb upstream of HFE) rs1800562 (C282Y) rs707889 (IVS6) rs2071303 (IVS2)*
* This IVS2 SNP is in LD with H63D in the British population (Dorak et al. unpublished data)
Other Iron-related Genes
HFE2 (HFE2A, HJV)
TFR2 (TFR2)
HFE4 (SLC40A1, Ferroportin, IREG1)
TFRC (TFR1, CD71)
HAMP (Hepcidin, HFE2B)
DMT1 (NRAMP2, SLC11A2), NRAMP1 (SLC11A1)
HEPH (Hephaestin)
CYBRD1 (DCYTB)
SLC39A14 (ZIP14)
Literature
Feder et al. Discovery of HFE. Nature Genet 1996
Hanson et al. Hereditary Hemochromatosis (HuGE Review). AJE 2001
Dorak et al. HFE and Childhood Leukaemia (HuGE Review). Genet Med 2005
Toomajian & Martin Kreitman. HFE Haplotype Structure. Genetics 2002
Swinkels et al. Hereditary Hemochromatosis, Clin Chem 2006
Coding Region SNPs within the human HFE Gene (NCBI dbSNP Build 127)
|
Region |
Contig |
mRNA |
dbSNP rs# |
Hetero- |
Function |
dbSNP |
Protein |
Codon |
Amino acid |
|
exon_2 |
16949347 |
264 |
N.D. |
nonsynonymous |
C |
Thr [T] |
2 |
35 |
|
|
|
|
|
|
N.D. |
contig reference |
T |
Met [M] |
2 |
35 |
|
|
16949430 |
347 |
0.127 |
nonsynonymous |
G |
Asp [D] |
1 |
63 |
|
|
|
|
|
|
0.127 |
contig reference |
C |
His [H] |
1 |
63 |
|
|
16949436 |
353 |
N.D. |
nonsynonymous |
T |
Cys [C] |
1 |
65 |
|
|
|
|
|
|
N.D. |
contig reference |
A |
Ser [S] |
1 |
65 |
|
|
16949520 |
437 |
N.D. |
nonsynonymous |
C |
Arg [R] |
1 |
93 |
|
|
|
|
|
|
N.D. |
contig reference |
G |
Gly [G] |
1 |
93 |
|
|
16949557 |
474 |
N.D. |
nonsynonymous |
C |
Thr [T] |
2 |
105 |
|
|
|
|
|
|
N.D. |
contig reference |
T |
Ile [I] |
2 |
105 |
|
exon_3 |
16949833 |
541 |
N.D. |
nonsynonymous |
C |
His [H] |
3 |
127 |
|
|
|
|
|
|
N.D. |
contig reference |
A |
Gln [Q] |
3 |
127 |
|
exon_4 |
16951197 |
810 |
N.D. |
nonsynonymous |
T |
Ile [I] |
2 |
217 |
|
|
|
|
|
|
N.D. |
contig reference |
C |
Thr [T] |
2 |
217 |
|
|
16951392 |
1005 |
0.024 |
nonsynonymous |
A |
Tyr [Y] |
2 |
282 |
|
|
|
|
|
|
0.024 |
contig reference |
G |
Cys [C] |
2 |
282 |
|
exon_6 |
16952684 |
1186 |
0.053 |
synonymous |
T |
Tyr [Y] |
3 |
342 |
|
|
|
|
|
|
0.053 |
contig reference |
C |
Tyr [Y] |
3 |
342 |
All SNPs within the human HFE Gene (NCBI dbSNP Build 127)
|
Region |
Contig |
mRNA |
dbSNP rs# |
Hetero- |
Function |
dbSNP |
Protein |
Codon |
Amino acid |
|
exon_1 |
16945872 |
113 |
N.D. |
untranslated |
C/G |
|
|
|
|
|
intron_1 |
16946107 |
|
N.D. |
intron |
A/T |
|
|
|
|
|
|
16946540 |
|
0.062 |
intron |
A/T |
|
|
|
|
|
|
16946658 |
|
0.138 |
intron |
A/G |
|
|
|
|
|
|
16947141 |
|
0.495 |
intron |
A/C |
|
|
|
|
|
|
16947349 |
|
0.463 |
intron |
C/T |
|
|
|
|
|
|
16947587 |
|
N.D. |
intron |
A/C |
|
|
|
|
|
|
16948521 |
|
N.D. |
intron |
G/T |
|
|
|
|
|
|
16948644 |
|
N.D. |
intron |
A/T |
|
|
|
|
|
|
16948703 |
|
N.D. |
intron |
C/T |
|
|
|
|
|
|
16949254 |
|
0.474 |
intron |
C/T |
|
|
|
|
|
exon_2 |
16949347 |
264 |
N.D. |
nonsynonymous |
C |
Thr [T] |
2 |
35 |
|
|
|
|
|
|
N.D. |
contig reference |
T |
Met [M] |
2 |
35 |
|
|
16949430 |
347 |
0.127 |
nonsynonymous |
G |
Asp [D] |
1 |
63 |
|
|
|
|
|
|
0.127 |
contig reference |
C |
His [H] |
1 |
63 |
|
|
16949436 |
353 |
N.D. |
nonsynonymous |
T |
Cys [C] |
1 |
65 |
|
|
|
|
|
|
N.D. |
contig reference |
A |
Ser [S] |
1 |
65 |
|
|
16949520 |
437 |
N.D. |
nonsynonymous |
C |
Arg [R] |
1 |
93 |
|
|
|
|
|
|
N.D. |
contig reference |
G |
Gly [G] |
1 |
93 |
|
|
16949557 |
474 |
N.D. |
nonsynonymous |
C |
Thr [T] |
2 |
105 |
|
|
|
|
|
|
N.D. |
contig reference |
T |
Ile [I] |
2 |
105 |
|
intron_2 |
16949587 |
|
0.500 |
intron |
A/G |
|
|
|
|
|
exon_3 |
16949833 |
541 |
N.D. |
nonsynonymous |
C |
His [H] |
3 |
127 |
|
|
|
|
|
|
N.D. |
contig reference |
A |
Gln [Q] |
3 |
127 |
|
intron_3 |
16950099 |
|
0.284 |
intron |
C/T |
|
|
|
|
|
|
16950398 |
|
N.D. |
intron |
A/G |
|
|
|
|
|
|
16950421 |
|
N.D. |
intron |
A/C |
|
|
|
|
|
|
16950675 |
|
N.D. |
intron |
-/A |
|
|
|
|
|
|
16951116 |
|
0.242 |
intron |
C/G |
|
|
|
|
|
exon_4 |
16951197 |
810 |
N.D. |
nonsynonymous |
T |
Ile [I] |
2 |
217 |
|
|
|
|
|
|
N.D. |
contig reference |
C |
Thr [T] |
2 |
217 |
|
|
16951392 |
1005 |
0.024 |
nonsynonymous |
A |
Tyr [Y] |
2 |
282 |
|
|
|
|
|
|
0.024 |
contig reference |
G |
Cys [C] |
2 |
282 |
|
intron_4 |
16951487 |
|
0.027 |
intron |
A/G |
|
|
|
|
|
|
16951548 |
|
N.D. |
intron |
C/T |
|
|
|
|
|
|
16951554 |
|
0.443 |
intron |
C/T |
|
|
|
|
|
intron_5 |
16952277 |
|
0.236 |
intron |
G/T |
|
|
|
|
|
|
16952381 |
|
N.D. |
intron |
A/G |
|
|
|
|
|
|
16952618 |
|
0.357 |
intron |
A/G |
|
|
|
|
|
exon_6 |
16952684 |
1186 |
0.053 |
synonymous |
T |
Tyr [Y] |
3 |
342 |
|
|
|
|
|
|
0.053 |
contig reference |
C |
Tyr [Y] |
3 |
342 |
|
|
16953220 |
1722 |
N.D. |
untranslated |
C/T |
|
|
|
|
|
|
16953279 |
1781 |
0.020 |
untranslated |
A/G |
|
|
|
Other SNPs within the flanking regions of human HFE Gene
(NCBI dbSNP Build 127)
|
Contig |
Contig |
Contig |
dbSNP rs# |
Hetero- |
|
reference |
16944028 (5’) |
N.D. |
||
|
reference |
16944058 (5’) |
N.D. |
||
|
reference |
16944060 (5’) |
N.D. |
||
|
reference |
16944268 (5’) |
0.496 |
||
|
reference |
16944666 (5’) |
N.D. |
||
|
reference |
16944714 (5’) |
0.500 |
||
|
reference |
16944950 (5’) |
N.D. |
||
|
reference |
16945453 (5’) |
N.D. |
||
|
reference |
16955445 (3’) |
0.097 |
||
|
reference |
16955635 (3’) |
0.476 |
M.Tevfik DORAK, MD PhD
Last updated on 9 June 2012
Genetics Clinical Genetics Genetic Epidemiology Population Genetics Evolution HLA MHC Glossary Homepage