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UniProtKB/Swiss-Prot O15270: Variant p.Ala182Pro

Serine palmitoyltransferase 2
Gene: SPTLC2
Variant information

Variant position:  182
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Proline (P) at position 182 (A182P, p.Ala182Pro).
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 small size and hydrophobic (A) to medium size and hydrophobic (P)
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

Involvement in disease:  Neuropathy, hereditary sensory and autonomic, 1C (HSAN1C) [MIM:613640]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1C symptoms include loss of touch and vibration in the feet, dysesthesia and severe panmodal sensory loss in the upper and lower limbs, distal lower limb sensory loss with ulceration and osteomyelitis, and distal muscle weakness. {ECO:0000269|PubMed:20920666, ECO:0000269|PubMed:23658386, ECO:0000269|PubMed:26573920}. Note=The disease is caused by mutations affecting the gene represented in this entry. SPTLC2 disease mutations cause a shift in the substrate specificity of SPT resulting in the alternative use of L-alanine and L-glycine over its canonical substrate L-serine. This leads to the production of 1-deoxysphingolipids that cannot be correctly metabolized (PubMed:23658386). {ECO:0000269|PubMed:23658386, ECO:0000269|PubMed:26573920}.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HSAN1C; reduced activity with L-serine as substrate; increased activity toward L-alanine resulting in the accumulation of 1-deoxy-sphinganine.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  182
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  562
The length of the canonical sequence.

Location on the sequence:   YTGNIIKGVINMGSYNYLGF  A RNTGSCQEAAAKVLEEYGAG
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                         YTGNIIKGVINMGSYNYLGFARNTGSCQEAAAKVLEEYGAG

Mouse                         YTGNIIKGVINMGSYNYLGFARNTGSCQEAAAEVLKEYGAG

Rat                           YTGNIIKGVINMGSYNYLGFARNTGSCQEAAAEVLKTYGAG

Caenorhabditis elegans        YPGTRT-NVINVGSYNYLGFAQSAGPCAEQSASSIDREGLS

Slime mold                    LTGGKTIKCLNLGSYNYLGFAQNEGPVADKVIDSIYKYGVY

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.

TypePositionsDescription
Chain 1 – 562 Serine palmitoyltransferase 2


Literature citations

Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2.
Murphy S.M.; Ernst D.; Wei Y.; Laura M.; Liu Y.T.; Polke J.; Blake J.; Winer J.; Houlden H.; Hornemann T.; Reilly M.M.;
Neurology 80:2106-2111(2013)
Cited for: VARIANT HSAN1C PRO-182; CHARACTERIZATION OF VARIANT HSAN1C PRO-182; PATHOLOGICAL MECHANISM;

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.