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UniProtKB/Swiss-Prot Q96JX3: Variant p.Ser498Thr

Protein SERAC1
Gene: SERAC1
Variant information

Variant position:  498
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 Serine (S) to Threonine (T) at position 498 (S498T, p.Ser498Thr).
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 polar (S) to medium size and polar (T)
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:  3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL) [MIM:614739]: An autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome. Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells. {ECO:0000269|PubMed:22683713, ECO:0000269|PubMed:23707711, ECO:0000269|PubMed:28778788}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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 MEGDEL.
Any additional useful information about the variant.

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



Sequence information

Variant position:  498
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  654
The length of the canonical sequence.

Location on the sequence:   LLRKLRAAGVGDRPVVWISH  S MGGLLVKKMLLEASTKPEMS
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                         LLRKLRAAGVGDRPVVWISHSMGGLLVKKMLLEASTKPEMS

Mouse                         LLSKLRAAGVGDRPMIWISHSMGGLLVKKMLLEASKKPELN

Bovine                        LLRKLRAAGVGDRPVVWVSHSMGGLLVKKMLLEASKRPEMN

Zebrafish                     LLRKLKDAGVGERPVIWVAHSMGGLLVKKMLLDAAKDPDLS

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 – 654 Protein SERAC1
Alternative sequence 168 – 654 Missing. In isoform 3.
Alternative sequence 469 – 531 KSIAFRSNELLRKLRAAGVGDRPVVWISHSMGGLLVKKMLLEASTKPEMSTVINNTRGIIFYS -> RSLLSISSGIVEGLESPLHSEATNFLGSSELLVLGIGQWFGYHIAWEVFLSKRCCWKPLRSQK. In isoform 2.


Literature citations

Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.
Wortmann S.B.; Vaz F.M.; Gardeitchik T.; Vissers L.E.; Renkema G.H.; Schuurs-Hoeijmakers J.H.; Kulik W.; Lammens M.; Christin C.; Kluijtmans L.A.; Rodenburg R.J.; Nijtmans L.G.; Grunewald A.; Klein C.; Gerhold J.M.; Kozicz T.; van Hasselt P.M.; Harakalova M.; Kloosterman W.; Baric I.; Pronicka E.; Ucar S.K.; Naess K.; Singhal K.K.; Krumina Z.; Gilissen C.; van Bokhoven H.; Veltman J.A.; Smeitink J.A.; Lefeber D.J.; Spelbrink J.N.; Wevers R.A.; Morava E.; de Brouwer A.P.;
Nat. Genet. 44:797-802(2012)
Cited for: VARIANTS MEGDEL ASP-401; GLU-404; LEU-479 DEL AND THR-498; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

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.