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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

NCBI Global Search

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   

HapMap (isoform 1

 SNP@Ethnos: HFE      Diseasome: HFE      MutDB: HFE

Atlas of Genetics & Cytogenetics in Oncology & HematologyHFE   TFRC 

 Genetic Association Database: Gene View   &   Disease View 

HugeNet Navigator: HFE  TFRC

 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

Mouse Hfe

Expression Profiles: HFE   TFRC   HAMP   SLC11A2   SLC40A1

DOE Genomics

PubMed Search    Google Search    Medline Plus  

Hereditary Hemochromatosis:

Genes and Disease    Gene Reviews    CDC    NHGRI    Iron Disorders Institute    Wellcome Trust 

NHANES III Genetic Data: HFE

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:

SNPSeek: HFE   HAMP   TFRC

SNPs3D: HFE   TFRC

SiPEP: HFE   HAMP   TFRC

FastSNP: HFE   HAMP  TFRC

 

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)

TF   LTF   MFI2  

HAMP (Hepcidin, HFE2B)

DMT1 (NRAMP2, SLC11A2), NRAMP1 (SLC11A1)

HEPH (Hephaestin)

CYBRD1 (DCYTB)

RRM1   RRM2   RRM2B

TMPRSS6

BMP6

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

Davis & Dorak. An extensive analysis of the hereditary hemochromatosis gene HFE and neighboring histone genes. Ann Hematol 2010

Toomajian & Martin Kreitman. HFE Haplotype Structure. Genetics 2002

Swinkels et al. Hereditary Hemochromatosis, Clin Chem 2006

Mouse Hfe Literature

 

 

Coding Region SNPs within the human HFE Gene (NCBI dbSNP Build 127)

 

Region

Contig
position

mRNA
pos

dbSNP rs#
cluster id

Hetero-
zygosity

Function

dbSNP
allele

Protein
residue

Codon
pos

Amino acid
pos

exon_2

16949347

264

rs2242956

N.D.

nonsynonymous

C

Thr [T]

2

35

 

 

 

 

N.D.

contig reference

T

Met [M]

2

35

 

16949430

347

rs1799945

0.127

nonsynonymous

G

Asp [D]

1

63

 

 

 

 

0.127

contig reference

C

His [H]

1

63

 

16949436

353

rs1800730

N.D.

nonsynonymous

T

Cys [C]

1

65

 

 

 

 

N.D.

contig reference

A

Ser [S]

1

65

 

16949520

437

rs28934597

N.D.

nonsynonymous

C

Arg [R]

1

93

 

 

 

 

N.D.

contig reference

G

Gly [G]

1

93

 

16949557

474

rs28934596

N.D.

nonsynonymous

C

Thr [T]

2

105

 

 

 

 

N.D.

contig reference

T

Ile [I]

2

105

exon_3

16949833

541

rs28934595

N.D.

nonsynonymous

C

His [H]

3

127

 

 

 

 

N.D.

contig reference

A

Gln [Q]

3

127

exon_4

16951197

810

rs4986950

N.D.

nonsynonymous

T

Ile [I]

2

217

 

 

 

 

N.D.

contig reference

C

Thr [T]

2

217

 

16951392

1005

rs1800562

0.024

nonsynonymous

A

Tyr [Y]

2

282

 

 

 

 

0.024

contig reference

G

Cys [C]

2

282

exon_6

16952684

1186

rs35201683

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
position

mRNA
pos

dbSNP rs#
cluster id

Hetero-
zygosity

Function

dbSNP
allele

Protein
residue

Codon
pos

Amino acid
pos

exon_1

16945872

113

rs41266793

N.D.

untranslated

C/G

 

 

 

intron_1

16946107

 

rs2858993

N.D.

intron

A/T

 

 

 

 

16946540

 

rs807206

0.062

intron

A/T

 

 

 

 

16946658

 

rs3799374

0.138

intron

A/G

 

 

 

 

16947141

 

rs2794719

0.495

intron

A/C

 

 

 

 

16947349

 

rs9366637

0.463

intron

C/T

 

 

 

 

16947587

 

rs807207

N.D.

intron

A/C

 

 

 

 

16948521

 

rs34555420

N.D.

intron

G/T

 

 

 

 

16948644

 

rs2858994

N.D.

intron

A/T

 

 

 

 

16948703

 

rs13196986

N.D.

intron

C/T

 

 

 

 

16949254

 

rs2227837

0.474

intron

C/T

 

 

 

exon_2

16949347

264

rs2242956

N.D.

nonsynonymous

C

Thr [T]

2

35

 

 

 

 

N.D.

contig reference

T

Met [M]

2

35

 

16949430

347

rs1799945

0.127

nonsynonymous

G

Asp [D]

1

63

 

 

 

 

0.127

contig reference

C

His [H]

1

63

 

16949436

353

rs1800730

N.D.

nonsynonymous

T

Cys [C]

1

65

 

 

 

 

N.D.

contig reference

A

Ser [S]

1

65

 

16949520

437

rs28934597

N.D.

nonsynonymous

C

Arg [R]

1

93

 

 

 

 

N.D.

contig reference

G

Gly [G]

1

93

 

16949557

474

rs28934596

N.D.

nonsynonymous

C

Thr [T]

2

105

 

 

 

 

N.D.

contig reference

T

Ile [I]

2

105

intron_2

16949587

 

rs2071303

0.500

intron

A/G

 

 

 

exon_3

16949833

541

rs28934595

N.D.

nonsynonymous

C

His [H]

3

127

 

 

 

 

N.D.

contig reference

A

Gln [Q]

3

127

intron_3

16950099

 

rs2227838

0.284

intron

C/T

 

 

 

 

16950398

 

rs807208

N.D.

intron

A/G

 

 

 

 

16950421

 

rs2032451

N.D.

intron

A/C

 

 

 

 

16950675

 

rs34225963

N.D.

intron

-/A

 

 

 

 

16951116

 

rs807209

0.242

intron

C/G

 

 

 

exon_4

16951197

810

rs4986950

N.D.

nonsynonymous

T

Ile [I]

2

217

 

 

 

 

N.D.

contig reference

C

Thr [T]

2

217

 

16951392

1005

rs1800562

0.024

nonsynonymous

A

Tyr [Y]

2

282

 

 

 

 

0.024

contig reference

G

Cys [C]

2

282

intron_4

16951487

 

rs1800758

0.027

intron

A/G

 

 

 

 

16951548

 

rs2794717

N.D.

intron

C/T

 

 

 

 

16951554

 

rs1800708

0.443

intron

C/T

 

 

 

intron_5

16952277

 

rs2858996

0.236

intron

G/T

 

 

 

 

16952381

 

rs2071302

N.D.

intron

A/G

 

 

 

 

16952618

 

rs1572982

0.357

intron

A/G

 

 

 

exon_6

16952684

1186

rs35201683

0.053

synonymous

T

Tyr [Y]

3

342

 

 

 

 

0.053

contig reference

C

Tyr [Y]

3

342

 

16953220

1722

rs3177318

N.D.

untranslated

C/T

 

 

 

 

16953279

1781

rs1045533

0.020

untranslated

A/G

 

 

 

 

 

Other SNPs within the flanking regions of human HFE Gene

(NCBI dbSNP Build 127)

 

Contig
Label

Contig
Accession

Contig
position

dbSNP rs#
cluster id

Hetero-
zygosity

reference

NT_007592

16944028 (5)

rs1971509

N.D.

reference

NT_007592

16944058 (5)

rs1971508

N.D.

reference

NT_007592

16944060 (5)

rs7741769

N.D.

reference

NT_007592

16944268 (5)

rs2006736

0.496

reference

NT_007592

16944666 (5)

rs35646118

N.D.

reference

NT_007592

16944714 (5)

rs1800702

0.500

reference

NT_007592

16944950 (5)

rs1061482

N.D.

reference

NT_007592

16945453 (5)

rs2794720

N.D.

reference

NT_007592

16955445 (3)

rs17596719

0.097

reference

NT_007592

16955635 (3)

rs6918586

0.476

 

 

 

M.Tevfik DORAK, MD PhD

 

Last updated on 9 June 2012

 

http://www.dorak.info

 

 

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