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UniProtKB/Swiss-Prot P00918: Variant p.Gly144Arg

Carbonic anhydrase 2
Gene: CA2
Chromosomal location: 8q22
Variant information

Variant position:  144
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 Glycine (G) to Arginine (R) at position 144 (G144R, p.Gly144Arg).
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 glycine (G) to large size and basic (R)
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:  Osteopetrosis, autosomal recessive 3 (OPTB3) [MIM:259730]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation. {ECO:0000269|PubMed:15300855, ECO:0000269|PubMed:1542674, ECO:0000269|PubMed:1928091, ECO:0000269|PubMed:8834238, ECO:0000269|PubMed:9143915}. 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 OPTB3; complete loss of activity.
Any additional useful information about the variant.



Sequence information

Variant position:  144
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  260
The length of the canonical sequence.

Location on the sequence:   NTKYGDFGKAVQQPDGLAVL  G IFLKVGSAKPGLQKVVDVLD
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                         NTK-YGDFGKAVQQPDGLAVLGIFLKVGSAKP-GLQKVVDVLD

Mouse                         NTK-YGDFGKAVQQPDGLAVLGIFLKIGPASQ-GLQKVLEA

Rat                           NTK-YGDFGKAVQHPDGLAVLGIFLKIGPASQ-GLQKITEA

Bovine                        NTK-YGDFGTAAQQPDGLAVVGVFLKVGDANP-ALQKVLDA

Rabbit                        NTK-YGDFGKAVKHPDGLAVLGIFLKIGSATP-GLQKVVDT

Sheep                         NTK-YGDFGTAAQQPDGLAVVGVFLKVGDANP-ALQKVLDV

Chicken                       NVK-YGKFAEALKHPDGLAVVGIFMKVGNAKP-EIQKVVDA

Caenorhabditis elegans        NSALYPNFSVAMTSPRGLLAVSVIVDIGKTTSVELRRLTVA

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 2 – 260 Carbonic anhydrase 2
Domain 3 – 259 Alpha-carbonic anhydrase
Active site 127 – 127
Mutagenesis 142 – 142 V -> FY. Strongly impaired activity.
Mutagenesis 142 – 142 V -> G. Weakly impaired activity.
Mutagenesis 142 – 142 V -> H. Impaired activity.
Beta strand 139 – 151


Literature citations

Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation.
Shah G.N.; Bonapace G.; Hu P.Y.; Strisciuglio P.; Sly W.S.;
Hum. Mutat. 24:272-272(2004)
Cited for: VARIANTS OPTB3 PRO-92; TYR-94; TYR-107 AND ARG-144; CHARACTERIZATION OF VARIANTS TYR-94 AND ARG-144;

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.