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UniProtKB/Swiss-Prot Q13510: Variant p.Thr42Met

Acid ceramidase
Gene: ASAH1
Variant information

Variant position:  42
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 Threonine (T) to Methionine (M) at position 42 (T42M, p.Thr42Met).
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

Involvement in disease:  Spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME) [MIM:159950]: An autosomal recessive neuromuscular disorder characterized by childhood onset of motor deficits and progressive myoclonic seizures, after normal developmental milestones. Proximal muscle weakness and generalized muscular atrophy are due to degeneration of spinal motor neurons. Myoclonic epilepsy is generally resistant to conventional therapy. The disease course is progressive and leads to respiratory muscle involvement and severe handicap or early death from respiratory insufficiency. {ECO:0000269|PubMed:22703880, ECO:0000269|PubMed:24164096, ECO:0000269|PubMed:27026573}. 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 SMAPME; results in reduced activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  42
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  395
The length of the canonical sequence.

Location on the sequence:   QHAPPWTEDCRKSTYPPSGP  T YRGAVPWYTINLDLPPYKRW
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                         QHAPPWTEDC----RKSTYPPSGPTYRGAVPWYTINLDLPPYKRW

Chimpanzee                    QHAPPWTEDC----RKSTYPPSGPTYRGPVPWYTINLDLPP

Mouse                         QDVPPWTEDC----RKSTYPPSGPTYRGPVPWHTINLDLPP

Rat                           QQVPPWTEDC----RKSTYPPSGPTYRGPVPWYTINLDLPP

Bovine                        QQVPPWTEDC----RKSTYPPSGPTYRGPVPWYTINLDLPP

Caenorhabditis elegans        ELPAPFKDHCILDDKQNLYDPSKQF---DIKWYDVNLDLPP

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 22 – 142 Acid ceramidase subunit alpha
Disulfide bond 31 – 340 Interchain (between alpha and beta subunits)
Alternative sequence 42 – 42 T -> TVFPAVIR. In isoform 3.


Literature citations

Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1.
Zhou J.; Tawk M.; Tiziano F.D.; Veillet J.; Bayes M.; Nolent F.; Garcia V.; Servidei S.; Bertini E.; Castro-Giner F.; Renda Y.; Carpentier S.; Andrieu-Abadie N.; Gut I.; Levade T.; Topaloglu H.; Melki J.;
Am. J. Hum. Genet. 91:5-14(2012)
Cited for: VARIANT SMAPME MET-42; CHARACTERIZATION OF VARIANT SMAPME MET-42; CATALYTIC ACTIVITY;

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.