UniProtKB/Swiss-Prot Q92851: Variant p.Ile406Leu

Caspase-10
Gene: CASP10
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Variant information Variant position:

406 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 Isoleucine (I) to Leucine (L) at position 406 (I406L, p.Ile406Leu). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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:

The mutant protein has defective apoptosis and exerts a dominant-negative effect when cotransfected with the wild-type protein. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs80358239 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

CPRLAEKPKLFFIQACQGEE I QPSVSIEADALNPEQAPTSL 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                         CPRLAEKPKLFFIQACQGEEIQPSVSIEADALNPEQAPTSL

Zebrafish                     CPALRDKPKVILIQACRGGEHGRVWASDGEPDEPIEIED--

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	220 – 415	Caspase-10 subunit p23/17
Active site	401 – 401
Alternative sequence	248 – 521	Missing. In isoform 7.
Alternative sequence	274 – 521	Missing. In isoform C.
Mutagenesis	401 – 401	C -> A. Abolishes proteolytic activity.

Literature citations
Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome.
Zhu S.; Hsu A.P.; Vacek M.M.; Zheng L.; Schaeffer A.A.; Dale J.K.; Davis J.; Fischer R.E.; Straus S.E.; Boruchov D.; Saulsbury F.T.; Lenardo M.J.; Puck J.M.;
Hum. Genet. 119:284-294(2006)
Cited for: VARIANTS LEU-406; ILE-410 AND CYS-446; CHARACTERIZATION OF VARIANTS LEU-406; ILE-410 AND CYS-446; Atypical presentation of autoimmune lymphoproliferative syndrome due to CASP10 mutation.
Tripodi S.I.; Mazza C.; Moratto D.; Ramenghi U.; Caorsi R.; Gattorno M.; Badolato R.;
Immunol. Lett. 177:22-24(2016)
Cited for: VARIANT LEU-406; Analysis of protein-coding genetic variation in 60,706 humans.
Lek M.; Karczewski K.J.; Minikel E.V.; Samocha K.E.; Banks E.; Fennell T.; O'Donnell-Luria A.H.; Ware J.S.; Hill A.J.; Cummings B.B.; Tukiainen T.; Birnbaum D.P.; Kosmicki J.A.; Duncan L.E.; Estrada K.; Zhao F.; Zou J.; Pierce-Hoffman E.; Berghout J.; Cooper D.N.; Deflaux N.; DePristo M.; Do R.; Flannick J.; Fromer M.; Gauthier L.; Goldstein J.; Gupta N.; Howrigan D.; Kiezun A.; Kurki M.I.; Moonshine A.L.; Natarajan P.; Orozco L.; Peloso G.M.; Poplin R.; Rivas M.A.; Ruano-Rubio V.; Rose S.A.; Ruderfer D.M.; Shakir K.; Stenson P.D.; Stevens C.; Thomas B.P.; Tiao G.; Tusie-Luna M.T.; Weisburd B.; Won H.H.; Yu D.; Altshuler D.M.; Ardissino D.; Boehnke M.; Danesh J.; Donnelly S.; Elosua R.; Florez J.C.; Gabriel S.B.; Getz G.; Glatt S.J.; Hultman C.M.; Kathiresan S.; Laakso M.; McCarroll S.; McCarthy M.I.; McGovern D.; McPherson R.; Neale B.M.; Palotie A.; Purcell S.M.; Saleheen D.; Scharf J.M.; Sklar P.; Sullivan P.F.; Tuomilehto J.; Tsuang M.T.; Watkins H.C.; Wilson J.G.; Daly M.J.; MacArthur D.G.;
Nature 536:285-291(2016)
Cited for: VARIANT LEU-406;

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.