UniProtKB/Swiss-Prot O43464: Variant p.Gly399Ser

Serine protease HTRA2, mitochondrial
Gene: HTRA2
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Variant information Variant position:

399 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 Glycine (G) to Serine (S) at position 399 (G399S, p.Gly399Ser). 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 glycine (G) to small size and polar (S) 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:

May be a risk factor for Parkinson disease; reduced protease activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs72470545 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LREPSFPDVQHGVLIHKVIL G SPAHRAGLRPGDVILAIGEQ 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                         LREPSFP-DVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQ

Mouse                         LREPSFP-DVQHGVLIHKVILGSPAHRAGLRPGDVILAIGE

Bovine                        LREPSFP-DVQHGVLIHKVILDSPAHRAGLRPGDVILAIGE

Drosophila                    SRSQNMPSNLTHGVLVWKVIVGSPAHSGGLQPGDIVTHINK

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	134 – 458	Serine protease HTRA2, mitochondrial
Domain	364 – 445	PDZ
Alternative sequence	314 – 458	DGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRRYIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQMVQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE -> VSETSFLPRIPAPGQCGKGRFPLIQGCLVKFLSSSLLAISQYPTRSPQHLLVLLFGCPHPLLFV. In isoform 4.
Alternative sequence	372 – 403	Missing. In isoform 2 and isoform 3.

Literature citations
Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease.
Strauss K.M.; Martins L.M.; Plun-Favreau H.; Marx F.P.; Kautzmann S.; Berg D.; Gasser T.; Wszolek Z.; Mueller T.; Bornemann A.; Wolburg H.; Downward J.; Riess O.; Schulz J.B.; Krueger R.;
Hum. Mol. Genet. 14:2099-2111(2005)
Cited for: INVOLVEMENT IN PARK13; VARIANTS SER-141 AND SER-399; CHARACTERIZATION OF VARIANTS SER-141 AND SER-399; Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic mutations in neurologically normal controls.
Simon-Sanchez J.; Singleton A.B.;
Hum. Mol. Genet. 17:1988-1993(2008)
Cited for: VARIANTS CYS-12; LEU-128; SER-141; SER-227 AND SER-399; Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease.
Unal Gulsuner H.; Gulsuner S.; Mercan F.N.; Onat O.E.; Walsh T.; Shahin H.; Lee M.K.; Dogu O.; Kansu T.; Topaloglu H.; Elibol B.; Akbostanci C.; King M.C.; Ozcelik T.; Tekinay A.B.;
Proc. Natl. Acad. Sci. U.S.A. 111:18285-18290(2014)
Cited for: VARIANT SER-399; 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 SER-399;

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.