UniProtKB/Swiss-Prot Q14790: Variant p.Asp285His

Caspase-8
Gene: CASP8
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Variant information Variant position:

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

LB/B 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 Aspartate (D) to Histidine (H) at position 285 (D285H, p.Asp285His). 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 acidic (D) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-1 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
Polymorphism:

Genetic variations in CASP8 are associated with reduced risk of lung cancer [MIM:211980] in a population of Han Chinese subjects. Genetic variations are also associated with decreased risk of cancer of various other forms including esophageal, gastric, colorectal, cervical, and breast, acting in an allele dose-dependent manner. Additional information on the polymorphism described.
Variant description:

Associated with protection against breast cancer; also associated with a lower risk of cutaneous melanoma. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1045485 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LDAGALTTTFEELHFEIKPH D DCTVEQIYEILKIYQLMDHS 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                         LDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQLMDHS-

Mouse                         CDKEALSKTFKELHFEIVSYDDCTANEIHEILEGYQSADHK

Rat                           YDEEALSKTFKELHFEIVSFSDCTASQIHEVLVSYQSKDHK

Drosophila                    VDKERLIEVFSSMGYNVEAYDNVDHMGIIERIRS--ACDRS

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	217 – 374	Caspase-8 subunit p18
Alternative sequence	221 – 479	Missing. In isoform 6.
Alternative sequence	236 – 479	Missing. In isoform 5.
Alternative sequence	277 – 479	Missing. In isoform 7 and isoform 8.
Beta strand	280 – 286

Literature citations
In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.
Fernandes-Alnemri T.; Armstrong R.C.; Krebs J.F.; Srinivasula S.M.; Wang L.; Bullrich F.; Fritz L.C.; Trapani J.A.; Tomaselli K.J.; Litwack G.; Alnemri E.S.;
Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4); FUNCTION; VARIANT HIS-285; FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.
Srinivasula S.M.; Ahmad M.; Ottilie S.; Bullrich F.; Banks S.; Wang Y.; Fernandes-Alnemri T.; Croce C.M.; Litwack G.; Tomaselli K.J.; Armstrong R.C.; Alnemri E.S.;
J. Biol. Chem. 272:18542-18545(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); VARIANT HIS-285; Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2.
Hadano S.; Yanagisawa Y.; Skaug J.; Fichter K.; Nasir J.; Martindale D.; Koop B.F.; Scherer S.W.; Nicholson D.W.; Rouleau G.A.; Ikeda J.-E.; Hayden M.R.;
Genomics 71:200-213(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT HIS-285; Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS THR-219 AND HIS-285; Association of a common variant of the CASP8 gene with reduced risk of breast cancer.
MacPherson G.; Healey C.S.; Teare M.D.; Balasubramanian S.P.; Reed M.W.R.; Pharoah P.D.; Ponder B.A.J.; Meuth M.; Bhattacharyya N.P.; Cox A.;
J. Natl. Cancer Inst. 96:1866-1869(2004)
Cited for: VARIANT HIS-285; PROTECTION AGAINST BREAST CANCER; A common coding variant in CASP8 is associated with breast cancer risk.
Cox A.; Dunning A.M.; Garcia-Closas M.; Balasubramanian S.; Reed M.W.R.; Pooley K.A.; Scollen S.; Baynes C.; Ponder B.A.J.; Chanock S.; Lissowska J.; Brinton L.; Peplonska B.; Southey M.C.; Hopper J.L.; McCredie M.R.E.; Giles G.G.; Fletcher O.; Johnson N.; dos Santos Silva I.; Gibson L.; Bojesen S.E.; Nordestgaard B.G.; Axelsson C.K.; Torres D.; Hamann U.; Justenhoven C.; Brauch H.; Chang-Claude J.; Kropp S.; Risch A.; Wang-Gohrke S.; Schuermann P.; Bogdanova N.; Doerk T.; Fagerholm R.; Aaltonen K.; Blomqvist C.; Nevanlinna H.; Seal S.; Renwick A.; Stratton M.R.; Rahman N.; Sangrajrang S.; Hughes D.; Odefrey F.; Brennan P.; Spurdle A.B.; Chenevix-Trench G.; Beesley J.; Mannermaa A.; Hartikainen J.; Kataja V.; Kosma V.M.; Couch F.J.; Olson J.E.; Goode E.L.; Broeks A.; Schmidt M.K.; Hogervorst F.B.L.; Van't Veer L.J.; Kang D.; Yoo K.-Y.; Noh D.-Y.; Ahn S.-H.; Wedren S.; Hall P.; Low Y.-L.; Liu J.; Milne R.L.; Ribas G.; Gonzalez-Neira A.; Benitez J.; Sigurdson A.J.; Stredrick D.L.; Alexander B.H.; Struewing J.P.; Pharoah P.D.P.; Easton D.F.;
Nat. Genet. 39:352-358(2007)
Cited for: VARIANT HIS-285; PROTECTION AGAINST BREAST CANCER; Genetic variants and haplotypes of the caspase-8 and caspase-10 genes contribute to susceptibility to cutaneous melanoma.
Li C.; Zhao H.; Hu Z.; Liu Z.; Wang L.-E.; Gershenwald J.E.; Prieto V.G.; Lee J.E.; Duvic M.; Grimm E.A.; Wei Q.;
Hum. Mutat. 29:1443-1451(2008)
Cited for: VARIANT HIS-285; RISK FACTOR FOR CUTANEOUS MELANOMA;

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.