UniProtKB/Swiss-Prot Q8IV08: Variant p.Leu308Pro

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

308 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 Leucine (L) to Proline (P) at position 308 (L308P, p.Leu308Pro). 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:

-3 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:

In SCA46; uncertain significance; reduced lysosomal localization; induces retention in the ER; reduction of proteolityc cleavage; loss of exonuclease activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs537053537 [ dbSNP | Ensembl ]

Sequence information Variant position:

308 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:

ALAYLASAPPPLCPSGRTPD L KALLNVVDNARSFIYVAVMN 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                         ALAYLASAPPPLCPSGRTPDLKALLNVVDNARSFIYVAVMN

Mouse                         ALAYLASAPPPLCPSGRTPDLKALLNVVDSARSFIYIAVMN

Rat                           ALAYLASAPPPLCPGGRTPDLKALLSVVDNARSFIYIAVMN

Bovine                        ALAYLASAPPPLCPSGRTPDLKALLNVVDNARSFIYIAVMN

Xenopus laevis                SQVYLSSSPPPLSATGRTDDLQSIMNIIDDAKKFVYISVMD

Xenopus tropicalis            SQVYISSSPPPLSATGRTDDLQSIINIIDDAKKFVYISVMD

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 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; Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.
Nibbeling E.A.R.; Duarri A.; Verschuuren-Bemelmans C.C.; Fokkens M.R.; Karjalainen J.M.; Smeets C.J.L.M.; de Boer-Bergsma J.J.; van der Vries G.; Dooijes D.; Bampi G.B.; van Diemen C.; Brunt E.; Ippel E.; Kremer B.; Vlak M.; Adir N.; Wijmenga C.; van de Warrenburg B.P.C.; Franke L.; Sinke R.J.; Verbeek D.S.;
Brain 140:2860-2878(2017)
Cited for: INVOLVEMENT IN SCA46; VARIANT SCA46 PRO-308; GLYCOSYLATION; CHARACTERIZATION OF VARIANT SCA46 PRO-308; POSSIBLE; PLD3 and spinocerebellar ataxia.
Gonzalez A.C.; Stroobants S.; Reisdorf P.; Gavin A.L.; Nemazee D.; Schwudke D.; D'Hooge R.; Saftig P.; Damme M.;
Brain 141:E78-E78(2018)
Cited for: CHARACTERIZATION OF VARIANT SCA46 PRO-308; FUNCTION; SUBCELLULAR LOCATION; CATALYTIC ACTIVITY;

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.