UniProtKB/Swiss-Prot P31645: Variant p.Gly56Ala

Sodium-dependent serotonin transporter
Gene: SLC6A4
Feedback?

Variant information Variant position:

56 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 Alanine (A) at position 56 (G56A, p.Gly56Ala). 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 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
Polymorphism:

A polymorphism in the promoter region (5-HTT gene-linked polymorphic region, 5-HTTLPR) is located approximately 1 kb upstream of the transcription initiation site and is composed of 16 repeat elements. The polymorphism consists of a 44-bp insertion or deletion involving repeat elements 6 to 8. The short allele is associated with lower transcriptional efficiency of the promoter compared with the long allele. Over half of the Caucasian population has a short allele. Individuals with one or two copies of the short allele exhibit more depressive symptoms, diagnosable depression and suicidality in relation to stressful life events than individuals homozygous for the long allele.The 5-HTTLPR polymorphism may influence susceptibility to anxiety [MIM:607834]. - The polymorphism Val-425 seems to be linked to a susceptibility to obsessive-compulsive disorder (OCD) [MIM:164230]. - Genetic variations in SLC6A4 determine the genetic susceptibility to alcoholism [MIM:103780]. - Polymorphisms that alter SLC6A4 expression or function may increase the susceptibility to autism. - Additional information on the polymorphism described.
Variant description:

Found in 15 autistic individuals, decreased expression at the cell surface; increased affinity for serotonin; increased serotonin transport capacity; loss of regulation through cGMP and MAP kinases pathways; hypoplasia of the enteric nervous system and decreased gastrointestinal peristaltic reflexes shown by a mouse knockin model of the mutation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs6355 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

DKVESGQISNGYSAVPSPGA G DDTRHSIPATTTTLVAELHQ 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                         DKVESGQISNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQ

Rhesus macaque                DKVESGQISNGYSAVPSPGAGDDTRHSIPAATTTLVAELHQ

Mouse                         DKAGPGQISNGYSAVPSTSAGDEAPHSTPAATTTLVAEIHQ

Rat                           DRAEPSQISNGYSAVPSTSAGDEASHSIPAATTTLVAEIRQ

Bovine                        DKAESGQISNGYSAVPNPGAGDDTQHSIPAATTALVAEVHP

Drosophila                    NEDDSNE-DDGDHTTPAK-VTDPLAPKLANNERILVVSVTE

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 – 630	Sodium-dependent serotonin transporter
Topological domain	1 – 87	Cytoplasmic
Region	1 – 59	Disordered
Modified residue	47 – 47	Phosphotyrosine

Literature citations
Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS ALA-56 AND ASN-605; Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors.
Sutcliffe J.S.; Delahanty R.J.; Prasad H.C.; McCauley J.L.; Han Q.; Jiang L.; Li C.; Folstein S.E.; Blakely R.D.;
Am. J. Hum. Genet. 77:265-279(2005)
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO AUTISM; VARIANTS ALA-56; LEU-425; LEU-465 AND VAL-550; CHARACTERIZATION OF VARIANT ALA-56; Enhanced activity of human serotonin transporter variants associated with autism.
Prasad H.C.; Steiner J.A.; Sutcliffe J.S.; Blakely R.D.;
Philos. Trans. R. Soc. Lond., B, Biol. Sci. 364:163-173(2009)
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO AUTISM; CHARACTERIZATION OF VARIANTS ALA-56; LEU-425; LEU-465 AND VAL-550; POLYMORPHISM; FUNCTION; TRANSPORTER ACTIVITY; Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function.
Margolis K.G.; Li Z.; Stevanovic K.; Saurman V.; Israelyan N.; Anderson G.M.; Snyder I.; Veenstra-VanderWeele J.; Blakely R.D.; Gershon M.D.;
J. Clin. Invest. 126:2221-2235(2016)
Cited for: CHARACTERIZATION OF VARIANT ALA-56;

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.