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UniProtKB/Swiss-Prot Q13510: Variant p.Trp169Arg

Acid ceramidase
Gene: ASAH1
Variant information

Variant position:  169
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  US
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 Tryptophan (W) to Arginine (R) at position 169 (W169R, p.Trp169Arg).
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 large size and aromatic (W) to large size and basic (R)
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 FRBRL; unknown pathological significance.
Any additional useful information about the variant.

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

Sequence information

Variant position:  169
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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.







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.

Chain 143 – 395 Acid ceramidase subunit beta
Site 162 – 162 Important for catalytic activity
Glycosylation 173 – 173 N-linked (GlcNAc...) asparagine
Disulfide bond 31 – 340 Interchain (between alpha and beta subunits)
Mutagenesis 159 – 159 R -> Q. Strongly decreased autocatalytic processing. Moderately decreased ceramidase activity.
Mutagenesis 162 – 162 D -> N. Strongly decreased autocatalytic processing. Strongly decreased ceramidase activity.
Mutagenesis 169 – 171 WNI -> QNQ. Moderately decreased autocatalytic processing, but loss of ceramidase activity, when associated with Q-176.
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.

Literature citations

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease.
Bonafe L.; Kariminejad A.; Li J.; Royer-Bertrand B.; Garcia V.; Mahdavi S.; Bozorgmehr B.; Lachman R.L.; Mittaz-Crettol L.; Campos-Xavier B.; Nampoothiri S.; Unger S.; Rivolta C.; Levade T.; Superti-Furga A.;
Arthritis Rheum. 68:2323-2327(2016)
Cited for: VARIANTS FRBRL ARG-169 AND GLY-254;

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.