Home  |  Contact

UniProtKB/Swiss-Prot Q13510: Variant p.Leu182Val

Acid ceramidase
Gene: ASAH1
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 Leucine (L) to Valine (V) at position 182 (L182V, p.Leu182Val).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Farber lipogranulomatosis (FRBRL) [MIM:228000]: An autosomal recessive lysosomal storage disorder characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, and marked accumulation of ceramide in lysosomes. Disease severity is variable. The most severe disease subtype is a rare neonatal form with death occurring before 1 year of age. {ECO:0000269|PubMed:10610716, ECO:0000269|PubMed:10993717, ECO:0000269|PubMed:11241842, ECO:0000269|PubMed:12638942, ECO:0000269|PubMed:16951918, ECO:0000269|PubMed:20609603, ECO:0000269|PubMed:21893389, ECO:0000269|PubMed:21982811, ECO:0000269|PubMed:26945816, ECO:0000269|PubMed:27411168, ECO:0000269|PubMed:8955159}. 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 FRBRL.
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:  395
The length of the canonical sequence.

Location on the sequence:   DFGVFLGWNINNDTWVITEQ  L KPLTVNLDFQRNNKTVFKAS
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                         DFGVFLGWNINNDTWVITEQLKPLTVNLDFQRNNKTVFKAS

Chimpanzee                    DFGVFLGWNINNDTWVITEQLKPLTVNLDFQRNNKTVFKAS

Mouse                         DFGIFLGWNINNNTWVVTEELKPLTVNLDFQRNNKTVFKAT

Rat                           DFGIFLGWNINNNTWVVTEELKPLTVNLDFQRNNKTVFKAT

Bovine                        DFGVFLGWNINNDTWVITEELKPLTVNLDFQRNNKTLFKAT

Caenorhabditis elegans        DFGLFMGWDPVLHDWQISQKLRKMIINVNWLKDGKLLYKSN

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 143 – 395 Acid ceramidase subunit beta
Site 162 – 162 Important for catalytic activity
Glycosylation 173 – 173 N-linked (GlcNAc...) asparagine
Glycosylation 195 – 195 N-linked (GlcNAc...) asparagine
Disulfide bond 31 – 340 Interchain (between alpha and beta subunits)
Mutagenesis 162 – 162 D -> N. Strongly decreased autocatalytic processing. Strongly decreased ceramidase activity.
Mutagenesis 173 – 173 N -> Q. Loss of ceramide catabolic process.
Mutagenesis 176 – 176 W -> Q. Moderately decreased autocatalytic processing, but loss of ceramidase activity, when associated with 169-Q--Q-171.
Mutagenesis 195 – 195 N -> Q. No effect on ceramide catabolic process.
Helix 177 – 182


Literature citations

Farber lipogranulomatosis: clinical and molecular genetic analysis reveals a novel mutation in an Indian family.
Devi A.R.R.; Gopikrishna M.; Ratheesh R.; Savithri G.; Swarnalata G.; Bashyam M.;
J. Hum. Genet. 51:811-814(2006)
Cited for: VARIANT FRBRL VAL-182;

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.