UniProtKB/SwissProt variant VAR

Variant information

Variant position:

172

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

LP/P [Disclaimer]

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 Methionine (M) at position 172 (T172M, p.Thr172Met).

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 medium size and hydrophobic (M)

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:

In NEDMISBA; no effect on cell membrane localization; loss of LPC transport activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1057517688 [ dbSNP | Ensembl ]

Sequence information

Variant position:

172

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

543

The length of the canonical sequence.

Location on the sequence:

FPHGQTYWYLLFYCLFETMV T CFHVPYSALTMFISTEQTER

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                         FPHGQT-----YWYLLFYCLFETMVTCFHVPYSALTMFISTEQTER

Mouse                         FPSGTESSHGFLWYLLFYCLFETLVTCFHVPYSALTMFIST

Xenopus tropicalis            FSGVSM----VIWYLVFYCLFQTLVTCFHVPYSALTMFISK

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 – 543	Sodium-dependent lysophosphatidylcholine symporter 1
Transmembrane	158 – 182	Helical
Alternative sequence	1 – 186	MAKGEGAESGSAAGLLPTSILQSTERPAQVKKEPKKKKQQLSVCNKLCYALGGAPYQVTGCALGFFLQIYLLDVAQKDEEVVFCFSSFQVGPFSASIILFVGRAWDAITDPLVGLCISKSPWTCLGRLMPWIIFSTPLAVIAYFLIWFVPDFPHGQTYWYLLFYCLFETMVTCFHVPYSALTMFIS -> MWLRWALSLPPSSCLWAEPGMPSQTPWWASASANPPGPAWVALCPGSSSPRPWPSLPTSSSGSCPTSHTARPIGTCFSIASLKQWSRVSMFPTRLSPCSSA. In isoform 3.
Mutagenesis	177 – 177	P -> T. Reduced expression; no effect on cell membrane localization; decreased LPC transport activity.

Literature citations

Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.
Guemez-Gamboa A.; Nguyen L.N.; Yang H.; Zaki M.S.; Kara M.; Ben-Omran T.; Akizu N.; Rosti R.O.; Rosti B.; Scott E.; Schroth J.; Copeland B.; Vaux K.K.; Cazenave-Gassiot A.; Quek D.Q.; Wong B.H.; Tan B.C.; Wenk M.R.; Gunel M.; Gabriel S.; Chi N.C.; Silver D.L.; Gleeson J.G.;
Nat. Genet. 47:809-813(2015)
Cited for: INVOLVEMENT IN NEDMISBA; VARIANTS NEDMISBA MET-172 AND LEU-179; CHARACTERIZATION OF VARIANTS NEDMISBA MET-172 AND LEU-179; FUNCTION; SUBCELLULAR LOCATION;

Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features.
Scala M.; Chua G.L.; Chin C.F.; Alsaif H.S.; Borovikov A.; Riazuddin S.; Riazuddin S.; Chiara Manzini M.; Severino M.; Kuk A.; Fan H.; Jamshidi Y.; Toosi M.B.; Doosti M.; Karimiani E.G.; Salpietro V.; Dadali E.; Baydakova G.; Konovalov F.; Lozier E.; O'Connor E.; Sabr Y.; Alfaifi A.; Ashrafzadeh F.; Striano P.; Zara F.; Alkuraya F.S.; Houlden H.; Maroofian R.; Silver D.L.;
Eur. J. Hum. Genet. 28:1509-1519(2020)
Cited for: VARIANTS NEDMISBA MET-172; MET-211; PHE-263; HIS-339 AND LEU-506; CHARACTERIZATION OF VARIANTS MET-211; PHE-263; HIS-339 AND LEU-506; MUTAGENESIS OF PRO-177; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8NA29: Variant p.Thr172Met