UniProtKB/SwissProt variant VAR

Variant information

Variant position:

138

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 Glutamate (E) to Valine (V) at position 138 (E138V, p.Glu138Val).

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 acidic (E) to medium size and hydrophobic (V)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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; loss of ceramidase activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137853594 [ dbSNP | Ensembl ]

Sequence information

Variant position:

138

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:

GIAAVTDIPLGEIISFNIFY E LFTICTSIVAEDKKGHLIHG

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                         GIAAVTDIPLGEIISFNIFYELFTICTSIVAEDKKGHLIHG

Chimpanzee                    GIAAVTDIPLGEIISFNIFYELFTICTSIVAEDKKGHLIHG

Mouse                         GIADVTGIPLGEIISFNIFYELFTMCTSIITEDEKGHLLHG

Rat                           GIADVTGIPLGEIISFNIFYELFTMCTSIITEDGKGHLLHG

Bovine                        GIAAVTEIPLGEIILFNIFYEFFTICTSIITEDKEGHLLHG

Caenorhabditis elegans        SIANATGIPLGQITMYNIFYEIFTVCTSVIAQDKDGHVFHA

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.

Type	Positions	Description
Chain	22 – 142	Acid ceramidase subunit alpha
Active site	143 – 143	Nucleophile
Disulfide bond	31 – 340	Interchain (between alpha and beta subunits)
Mutagenesis	141 – 141	T -> A. Decreased rate of autocatalytic processing.
Mutagenesis	143 – 143	C -> A. Loss of autocatalytic processing. Loss of ceramidase activity.
Helix	136 – 139

Literature citations

Human acid ceramidase gene: novel mutations in Farber disease.
Zhang Z.; Mandal A.K.; Mital A.; Popescu N.; Zimonjic D.; Moser A.; Moser H.; Mukherjee A.B.;
Mol. Genet. Metab. 70:301-309(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS FRBRL HIS-22; ASP-23; VAL-138; LYS-222 AND ASP-320; VARIANTS MET-72; VAL-93 AND ALA-246;

The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression.
Li C.M.; Park J.H.; He X.; Levy B.; Chen F.; Arai K.; Adler D.A.; Disteche C.M.; Koch J.; Sandhoff K.; Schuchman E.H.;
Genomics 62:223-231(1999)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; VARIANTS FRBRL VAL-138; GLY-254 AND ARG-362; CHARACTERIZATION OF VARIANTS FRBRL VAL-138; GLY-254 AND ARG-362; TISSUE SPECIFICITY;

UniProtKB/Swiss-Prot Q13510: Variant p.Glu138Val