UniProtKB/Swiss-Prot Q676U5: Variant p.Thr300Ala

Autophagy-related protein 16-1
Gene: ATG16L1
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Variant information Variant position:

300 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 Threonine (T) to Alanine (A) at position 300 (T300A, p.Thr300Ala). 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 (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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:

Risk factor for IBD10; has no effect on the stability of the protein under normal conditions; enhances the cleavage and the degradation mediated by activated CASP3; results in reduced autophagy and defective clearance of intestinal pathogens; impairs interaction with TMEM59; slows TMEM59 intracellular trafficking; increases production of type I IFNs. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2241880 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

TNIFGRRSVSSFPVPQDNVD T HPGSGKEVRVPATALCVFDA 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                         TNIFGRRSVSSFPVPQDNVDTHPGSGKEVRVPATALCVFDA

Mouse                         TNIFGRRSVSSIPVPQDIMDTHPASGKDVRVPTTASYVFDA

Caenorhabditis elegans        -------------MPDTNSNGDLLLGDS--VPSRAEFVLEC

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	1 – 607	Autophagy-related protein 16-1
Modified residue	287 – 287	Phosphoserine
Mutagenesis	299 – 299	D -> E. Prevents cleavage by activated CASP3.

Literature citations
Cloning and analysis of human Apg16L.
Zheng H.; Ji C.; Li J.; Jiang H.; Ren M.; Lu Q.; Gu S.; Mao Y.; Xie Y.;
DNA Seq. 15:303-305(2004)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT ALA-300; A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1.
Hampe J.; Franke A.; Rosenstiel P.; Till A.; Teuber M.; Huse K.; Albrecht M.; Mayr G.; De La Vega F.M.; Briggs J.; Guenther S.; Prescott N.J.; Onnie C.M.; Haesler R.; Sipos B.; Foelsch U.R.; Lengauer T.; Platzer M.; Mathew C.G.; Krawczak M.; Schreiber S.;
Nat. Genet. 39:207-211(2007)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 5); INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; VARIANT ALA-300; A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5.
Prescott N.J.; Fisher S.A.; Franke A.; Hampe J.; Onnie C.M.; Soars D.; Bagnall R.; Mirza M.M.; Sanderson J.; Forbes A.; Mansfield J.C.; Lewis C.M.; Schreiber S.; Mathew C.G.;
Gastroenterology 132:1665-1671(2007)
Cited for: VARIANT ALA-300; INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis.
Rioux J.D.; Xavier R.J.; Taylor K.D.; Silverberg M.S.; Goyette P.; Huett A.; Green T.; Kuballa P.; Barmada M.M.; Datta L.W.; Shugart Y.Y.; Griffiths A.M.; Targan S.R.; Ippoliti A.F.; Bernard E.-J.; Mei L.; Nicolae D.L.; Regueiro M.; Schumm L.P.; Steinhart A.H.; Rotter J.I.; Duerr R.H.; Cho J.H.; Daly M.J.; Brant S.R.;
Nat. Genet. 39:596-604(2007)
Cited for: VARIANT ALA-300; INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; ATG16L1 and IL23R are associated with inflammatory bowel diseases but not with celiac disease in the Netherlands.
Weersma R.K.; Zhernakova A.; Nolte I.M.; Lefebvre C.; Rioux J.D.; Mulder F.; van Dullemen H.M.; Kleibeuker J.H.; Wijmenga C.; Dijkstra G.;
Am. J. Gastroenterol. 103:621-627(2008)
Cited for: VARIANT ALA-300; INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; ATG16L1 and IL23 receptor (IL23R) genes are associated with disease susceptibility in Hungarian CD patients.
Lakatos P.L.; Szamosi T.; Szilvasi A.; Molnar E.; Lakatos L.; Kovacs A.; Molnar T.; Altorjay I.; Papp M.; Tulassay Z.; Miheller P.; Papp J.; Tordai A.; Andrikovics H.;
Dig. Liver Dis. 40:867-873(2008)
Cited for: VARIANT ALA-300; INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; Autophagy 16-like 1 rs2241880 G allele is associated with Crohn's disease in German children.
Lacher M.; Schroepf S.; Ballauff A.; Lohse P.; von Schweinitz D.; Kappler R.; Koletzko S.;
Acta Paediatr. 98:1835-1840(2009)
Cited for: VARIANT ALA-300; INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; Autophagy gene ATG16L1 but not IRGM is associated with Crohn's disease in Canadian children.
Amre D.K.; Mack D.R.; Morgan K.; Krupoves A.; Costea I.; Lambrette P.; Grimard G.; Dong J.; Feguery H.; Bucionis V.; Deslandres C.; Levy E.; Seidman E.G.;
Inflamm. Bowel Dis. 15:501-507(2009)
Cited for: VARIANT ALA-300; INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; Autophagy genes variants and paediatric Crohn's disease phenotype: a single-centre experience.
Strisciuglio C.; Auricchio R.; Martinelli M.; Staiano A.; Giugliano F.P.; Andreozzi M.; De Rosa M.; Giannetti E.; Gianfrani C.; Izzo P.; Troncone R.; Miele E.;
Dig. Liver Dis. 46:512-517(2014)
Cited for: VARIANT ALA-300; INVOLVEMENT IN SUSCEPTIBILITY TO IBD10; A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3.
Murthy A.; Li Y.; Peng I.; Reichelt M.; Katakam A.K.; Noubade R.; Roose-Girma M.; Devoss J.; Diehl L.; Graham R.R.; van Lookeren Campagne M.;
Nature 506:456-462(2014)
Cited for: CHARACTERIZATION OF VARIANT ALA-300; FUNCTION IN AUTOPHAGY; CLEAVAGE BY CASP3; MUTAGENESIS OF ASP-299; The Thr300Ala variant in ATG16L1 is associated with improved survival in human colorectal cancer and enhanced production of type I interferon.
Grimm W.A.; Messer J.S.; Murphy S.F.; Nero T.; Lodolce J.P.; Weber C.R.; Logsdon M.F.; Bartulis S.; Sylvester B.E.; Springer A.; Dougherty U.; Niewold T.B.; Kupfer S.S.; Ellis N.; Huo D.; Bissonnette M.; Boone D.L.;
Gut 65:456-464(2016)
Cited for: CHARACTERIZATION OF VARIANT ALA-300; FUNCTION; The T300A Crohn's disease risk polymorphism impairs function of the WD40 domain of ATG16L1.
Boada-Romero E.; Serramito-Gomez I.; Sacristan M.P.; Boone D.L.; Xavier R.J.; Pimentel-Muinos F.X.;
Nat. Commun. 7:11821-11821(2016)
Cited for: CHARACTERIZATION OF VARIANT ALA-300; FUNCTION; INTERACTION WITH TMEM59;

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.