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UniProtKB/Swiss-Prot O15269: Variant p.Val144Asp

Serine palmitoyltransferase 1
Gene: SPTLC1
Variant information

Variant position:  144
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 Valine (V) to Aspartate (D) at position 144 (V144D, p.Val144Asp).
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 hydrophobic (V) to medium size and acidic (D)
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 HSAN1A; present with both painful and painles phenotypes; reduced activity; does not interfere with SPT complex formation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  144
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  473
The length of the canonical sequence.

Location on the sequence:   SLKKYGVGTCGPRGFYGTFD  V HLDLEDRLAKFMKTEEAIIY
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                         SLKKYGVGTCGPRGFYGTFDVHLDLEDRLAKFMKTEEAIIY

Mouse                         SLKKYGVGTCGPRGFYGTFDVHLDLEERLAKFMKTEEAIIY

Rat                           SLKKYGVGTCGPRGFYGTFDVHLDLEERLAKFMKTEEAIIY

Bovine                        SLKKYGVGTCGPRGFYGTFDVHLDLEDRLAKFMKTEEAIIY

Caenorhabditis elegans        TIFKYGVGSCGPRGFYGTVDVHLDLEKELAKFMGCEEAVLY

Slime mold                    AIRKYGVGSCGPRGFYGTIDVHLDLEKKTASFMKTPEAVLY

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 – 473 Serine palmitoyltransferase 1
Topological domain 37 – 473 Cytoplasmic
Modified residue 164 – 164 Phosphotyrosine; by ABL
Alternative sequence 143 – 143 D -> E. In isoform 2.
Alternative sequence 144 – 473 Missing. In isoform 2.
Mutagenesis 164 – 164 Y -> F. Increased serine palmitoyltransferase activity and sphingolipid content.


Literature citations

Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I.
Dawkins J.L.; Hulme D.J.; Brahmbhatt S.B.; Auer-Grumbach M.; Nicholson G.A.;
Nat. Genet. 27:309-312(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); VARIANTS HSAN1A TRP-133; TYR-133 AND ASP-144;

A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.
Hornemann T.; Penno A.; Richard S.; Nicholson G.; van Dijk F.S.; Rotthier A.; Timmerman V.; von Eckardstein A.;
Neurogenetics 10:135-143(2009)
Cited for: CHARACTERIZATION OF VARIANTS HSAN1A TYR-133; TRP-133 AND ASP-144; CHARACTERIZATION OF VARIANT ALA-387; LACK OF ASSOCIATION OF VARIANT ALA-387 WITH HSAN1A;

V144D Mutation of SPTLC1 Can Present with Both Painful and Painless Phenotypes in Hereditary Sensory and Autonomic Neuropathies Type I.
Ho K.W.D.; Jerath N.U.;
Case Rep. Genet. 2018:1898151-1898151(2018)
Cited for: VARIANT HSAN1A ASP-144;

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.