UniProtKB/Swiss-Prot Q30201: Variant p.Cys282Tyr

Hereditary hemochromatosis protein
Gene: HFE
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Variant information Variant position:

282 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Cysteine (C) to Tyrosine (Y) at position 282 (C282Y, p.Cys282Tyr). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from medium size and polar (C) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In HFE1; probable risk factor for porphyria cutanea tarda; correlated with increased serum transferrin levels; higher frequency in patients with type 2 diabetes than in controls. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1800562 [ dbSNP | Ensembl ]

Sequence information Variant position:

282 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

348 The length of the canonical sequence.
Location on the sequence:

GTYQGWITLAVPPGEEQRYT C QVEHPGLDQPLIVIWEPSPS The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWEPSPS

Chimpanzee                    GTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWEPSPS

Mouse                         ETYQGWLTLAVAPGDETRFTCQVEHPGLDQPLTASWEPLQS

Rat                           GTYQGWLTLAVAPGEETRFSCQVEHPGLDQPLTATWEPSRS

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	23 – 348	Hereditary hemochromatosis protein
Topological domain	23 – 306	Extracellular
Domain	207 – 298	Ig-like C1-type
Region	206 – 297	Alpha-3
Disulfide bond	225 – 282
Alternative sequence	27 – 298	Missing. In isoform 11.
Alternative sequence	162 – 348	Missing. In isoform 9.
Alternative sequence	277 – 348	Missing. In isoform 8.
Beta strand	280 – 285

Literature citations
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.
Feder J.N.; Gnirke A.; Thomas W.; Tsuchihashi Z.; Ruddy D.A.; Basava A.; Dormishian F.; Domingo R. Jr.; Ellis M.C. Jr.; Fullan A.; Hinton L.M.; Jones N.L.; Kimmel B.E.; Kronmal G.S.; Lauer P.; Lee V.K.; Loeb D.B.; Mapa F.A.; McClelland E.; Meyer N.C.; Mintier G.A.; Moeller N.; Moore T.; Morikang E.; Prass C.E.; Quintana L.; Starnes S.M.; Schatzman R.C.; Brunke K.J.; Drayna D.T.; Risch N.J.; Bacon B.R.; Wolff R.K.;
Nat. Genet. 13:399-409(1996)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT HFE1 TYR-282; VARIANT ASP-63; Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS MET-53; ASP-63; GLN-224 AND TYR-282; Mutation analysis of the HLA-H gene in Italian hemochromatosis patients.
Carella M.; D'Ambrosio L.; Totaro A.; Grifa A.; Valentino M.A.; Piperno A.; Girelli D.; Roetto A.; Franco B.; Gasparini P.; Camaschella C.;
Am. J. Hum. Genet. 60:828-832(1997)
Cited for: VARIANTS HFE1 ASP-63 AND TYR-282; Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic porphyria cutanea tarda.
Roberts A.G.; Whatley S.D.; Morgan R.R.; Worwood M.; Elder G.H.;
Lancet 349:321-323(1997)
Cited for: VARIANT HFE1 TYR-282; ASSOCIATION WITH PORPHYRIA CUTANEA TARDA; Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America.
Bonkovsky H.L.; Poh-Fitzpatrick M.; Pimstone N.; Obando J.; Di Bisceglie A.; Tattrie C.; Tortorelli K.; LeClair P.; Mercurio M.G.; Lambrecht R.W.;
Hepatology 27:1661-1669(1998)
Cited for: VARIANTS HFE1 ASP-63 AND TYR-282; HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis.
Mura C.; Raguenes O.; Ferec C.;
Blood 93:2502-2505(1999)
Cited for: VARIANTS HFE1 ASP-63; CYS-65 AND TYR-282; A retrospective anonymous pilot study in screening newborns for HFE mutations in Scandinavian populations.
Merryweather-Clarke A.T.; Simonsen H.; Shearman J.D.; Pointon J.J.; Norgaard-Pedersen B.; Robson K.J.H.;
Hum. Mutat. 13:154-159(1999)
Cited for: VARIANTS HFE1 ASP-63 AND TYR-282; Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda.
Brady J.J.; Jackson H.A.; Roberts A.G.; Morgan R.R.; Whatley S.D.; Rowlands G.L.; Darby C.; Shudell E.; Watson R.; Paiker J.; Worwood M.W.; Elder G.H.;
J. Invest. Dermatol. 115:868-874(2000)
Cited for: VARIANTS ASP-63 AND TYR-282; Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy.
Moczulski D.K.; Grzeszczak W.; Gawlik B.;
Diabetes Care 24:1187-1191(2001)
Cited for: VARIANTS HFE1 ASP-63 AND TYR-282; ASSOCIATION WITH DIABETIC NEPHROPATHY SUSCEPTIBILITY; Comprehensive hereditary hemochromatosis genotyping.
Jones D.C.; Young N.T.; Pigott C.; Fuggle S.V.; Barnardo M.C.N.M.; Marshall S.E.; Bunce M.;
Tissue Antigens 60:481-488(2002)
Cited for: VARIANTS HFE1 CYS-65; TYR-282 AND ALA-295; Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload.
Biasiotto G.; Belloli S.; Ruggeri G.; Zanella I.; Gerardi G.; Corrado M.; Gobbi E.; Albertini A.; Arosio P.;
Clin. Chem. 49:1981-1988(2003)
Cited for: VARIANTS HFE1 CYS-65; CYS-66; GLY-224 AND TYR-282; An unusual case of hemochromatosis due to a new compound heterozygosity in HFE (p.[Gly43Asp;His63Asp]+[Cys282Tyr]): structural implications with respect to binding with transferrin receptor 1.
Dupradeau F.-Y.; Pissard S.; Coulhon M.-P.; Cadet E.; Foulon K.; Fourcade C.; Goossens M.; Case D.A.; Rochette J.;
Hum. Mutat. 29:206-206(2008)
Cited for: VARIANTS HFE1 ASP-43; ASP-63 AND TYR-282;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.