UniProtKB/Swiss-Prot Q8IV08: Variant p.Val232Met

5'-3' exonuclease PLD3
Gene: PLD3
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Variant information Variant position:

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

US 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 Valine (V) to Methionine (M) at position 232 (V232M, p.Val232Met). 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:

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
Variant description:

Found in patients with Alzheimer disease; uncertain significance; does not reduce either amyloid-beta levels or APP expression. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs145999145 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

FYLGSANMDWRSLTQVKELG V VMYNCSCLARDLTKIFEAYW 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                         FYLGSANMDWRSLTQVKELGVVMYNCSCLARDLTKIFEAYW

Mouse                         FYLGSANMDWRSLTQVKELGVVMYNCSCLARDLTKIFEAYW

Rat                           FYLGSANMDWRSLTQVKELGVVMYNCSCLARDLTKIFEAYW

Bovine                        FYLGSANMDWRSLTQVKELGVVMYNCSCLARDLTKIFEAYW

Xenopus laevis                FYIGSANMDWRSLTQVKELGATIYNCSCLAQDLKKIFEAYW

Xenopus tropicalis            FYIGSANMDWRSLTQVKELGATIYNCSCLAEDLKKIFEAYW

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 – 490	5'-3' exonuclease PLD3
Topological domain	60 – 490	Lumenal

Literature citations
Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.
Cruchaga C.; Karch C.M.; Jin S.C.; Benitez B.A.; Cai Y.; Guerreiro R.; Harari O.; Norton J.; Budde J.; Bertelsen S.; Jeng A.T.; Cooper B.; Skorupa T.; Carrell D.; Levitch D.; Hsu S.; Choi J.; Ryten M.; Hardy J.; Ryten M.; Trabzuni D.; Weale M.E.; Ramasamy A.; Smith C.; Sassi C.; Bras J.; Gibbs J.R.; Hernandez D.G.; Lupton M.K.; Powell J.; Forabosco P.; Ridge P.G.; Corcoran C.D.; Tschanz J.T.; Norton M.C.; Munger R.G.; Schmutz C.; Leary M.; Demirci F.Y.; Bamne M.N.; Wang X.; Lopez O.L.; Ganguli M.; Medway C.; Turton J.; Lord J.; Braae A.; Barber I.; Brown K.; Passmore P.; Craig D.; Johnston J.; McGuinness B.; Todd S.; Heun R.; Kolsch H.; Kehoe P.G.; Hooper N.M.; Vardy E.R.; Mann D.M.; Pickering-Brown S.; Brown K.; Kalsheker N.; Lowe J.; Morgan K.; David Smith A.; Wilcock G.; Warden D.; Holmes C.; Pastor P.; Lorenzo-Betancor O.; Brkanac Z.; Scott E.; Topol E.; Morgan K.; Rogaeva E.; Singleton A.B.; Hardy J.; Kamboh M.I.; St George-Hyslop P.; Cairns N.; Morris J.C.; Kauwe J.S.; Goate A.M.;
Nature 505:550-554(2014)
Cited for: FUNCTION; POSSIBLE INVOLVEMENT IN ALZHEIMER DISEASE; VARIANT MET-232; TISSUE SPECIFICITY; INTERACTION WITH APP; Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a European consortium cohort.
Cacace R.; Van den Bossche T.; Engelborghs S.; Geerts N.; Laureys A.; Dillen L.; Graff C.; Thonberg H.; Chiang H.H.; Pastor P.; Ortega-Cubero S.; Pastor M.A.; Diehl-Schmid J.; Alexopoulos P.; Benussi L.; Ghidoni R.; Binetti G.; Nacmias B.; Sorbi S.; Sanchez-Valle R.; Llado A.; Gelpi E.; Almeida M.R.; Santana I.; Tsolaki M.; Koutroumani M.; Clarimon J.; Lleo A.; Fortea J.; de Mendonca A.; Martins M.; Borroni B.; Padovani A.; Matej R.; Rohan Z.; Vandenbulcke M.; Vandenberghe R.; De Deyn P.P.; Cras P.; van der Zee J.; Sleegers K.; Van Broeckhoven C.;
Hum. Mutat. 36:1226-1235(2015)
Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE; VARIANTS SER-63; ALA-76; MET-159; CYS-162; SER-173; GLY-175; CYS-188; HIS-222; MET-232; GLN-242; GLY-249; CYS-272; SER-284; VAL-293; LEU-297; TYR-300; PRO-308; ILE-358; ALA-426 AND ARG-429; PLD3 and sporadic Alzheimer's disease risk.
Lambert J.C.; Grenier-Boley B.; Bellenguez C.; Pasquier F.; Campion D.; Dartigues J.F.; Berr C.; Tzourio C.; Amouyel P.;
Nature 520:E1-E1(2015)
Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE; VARIANT MET-232; PLD3 variants in population studies.
van der Lee S.J.; Holstege H.; Wong T.H.; Jakobsdottir J.; Bis J.C.; Chouraki V.; van Rooij J.G.; Grove M.L.; Smith A.V.; Amin N.; Choi S.H.; Beiser A.S.; Garcia M.E.; van Ijcken W.F.; Pijnenburg Y.A.; Louwersheimer E.; Brouwer R.W.; van den Hout M.C.; Oole E.; Eirkisdottir G.; Levy D.; Rotter J.I.; Emilsson V.; O'Donnell C.J.; Aspelund T.; Uitterlinden A.G.; Launer L.J.; Hofman A.; Boerwinkle E.; Psaty B.M.; DeStefano A.L.; Scheltens P.; Seshadri S.; van Swieten J.C.; Gudnason V.; van der Flier W.M.; Ikram M.A.; van Duijn C.M.;
Nature 520:E2-E3(2015)
Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE; VARIANT MET-232; PLD3 in non-familial Alzheimer's disease.
Heilmann S.; Drichel D.; Clarimon J.; Fernandez V.; Lacour A.; Wagner H.; Thelen M.; Hernandez I.; Fortea J.; Alegret M.; Blesa R.; Mauleon A.; Roca M.R.; Kornhuber J.; Peters O.; Heun R.; Froelich L.; Huell M.; Heneka M.T.; Ruether E.; Riedel-Heller S.; Scherer M.; Wiltfang J.; Jessen F.; Becker T.; Tarraga L.; Boada M.; Maier W.; Lleo A.; Ruiz A.; Noethen M.M.; Ramirez A.;
Nature 520:E3-E5(2015)
Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE; VARIANT MET-232; PLD3 gene variants and Alzheimer's disease.
Hooli B.V.; Lill C.M.; Mullin K.; Qiao D.; Lange C.; Bertram L.; Tanzi R.E.;
Nature 520:E7-E8(2015)
Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE; VARIANT MET-232; Cruchaga & Goate reply.
Cruchaga C.; Goate A.M.;
Nature 520:E10-E10(2015)
Cited for: POSSIBLE INVOLVEMENT IN ALZHEIMER DISEASE; VARIANT MET-232; PLD3 gene and processing of APP.
Fazzari P.; Horre K.; Arranz A.M.; Frigerio C.S.; Saito T.; Saido T.C.; De Strooper B.;
Nature 541:E1-E2(2017)
Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS MET-232; FUNCTION; MUTAGENESIS OF LYS-418;

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.