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UniProtKB/Swiss-Prot Q8N2K0: Variant p.Thr253Arg

Lysophosphatidylserine lipase ABHD12
Gene: ABHD12
Chromosomal location: 20p11.21
Variant information

Variant position:  253
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 Arginine (R) at position 253 (T253R, p.Thr253Arg).
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 large size and basic (R)
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:  Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) [MIM:612674]: A slowly progressive neurologic disorder with a variable phenotype resembling Refsum disease. Clinical features include sensorineural hearing loss, visual problems related to cataracts, retinitis pigmentosa, pes cavus, ataxic and/or spastic gait disturbances with a progressive sensorimotor peripheral neuropathy. Other features include hyporeflexia, hyperreflexia, extensor plantar responses. {ECO:0000269|PubMed:20797687, ECO:0000269|PubMed:22938382, ECO:0000269|PubMed:24027063, ECO:0000269|PubMed:24697911, ECO:0000269|PubMed:25743180, ECO:0000269|PubMed:27890673, ECO:0000269|PubMed:29571850}. 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 PHARC; abolished monoacyglycerol lipase activity.
Any additional useful information about the variant.



Sequence information

Variant position:  253
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  398
The length of the canonical sequence.

Location on the sequence:   ARSGDNPVYIWGHSLGTGVA  T NLVRRLCERETPPDALILES
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                         ARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILES

Mouse                         ARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILES

Rat                           ARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILES

Bovine                        VRSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILES

Chicken                       ARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPEALILES

Xenopus tropicalis            ARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDSLILES

Zebrafish                     QRIGPKPLYIWGHSLGTGVATNLVRRLCDRGTPPDALILES

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 – 398 Lysophosphatidylserine lipase ABHD12
Topological domain 96 – 398 Extracellular
Active site 246 – 246 Nucleophile
Mutagenesis 246 – 246 S -> A. Loss of lipase activity.


Literature citations

Functional validation of ABHD12 mutations in the neurodegenerative disease PHARC.
Tingaud-Sequeira A.; Raldua D.; Lavie J.; Mathieu G.; Bordier M.; Knoll-Gellida A.; Rambeau P.; Coupry I.; Andre M.; Malm E.; Moeller C.; Andreasson S.; Rendtorff N.D.; Tranebjaerg L.; Koenig M.; Lacombe D.; Goizet C.; Babin P.J.;
Neurobiol. Dis. 98:36-51(2017)
Cited for: VARIANT PHARC ARG-253; CHARACTERIZATION OF VARIANTS PHARC ILE-202; ARG-253 AND 352-ARG--HIS-398 DEL;

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.