Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43570: Variant p.Glu143Lys

Carbonic anhydrase 12
Gene: CA12
Feedback?
Variant information Variant position: help 143 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Glutamate (E) to Lysine (K) at position 143 (E143K, p.Glu143Lys). 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: help Change from medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In HYCHL; severe decrease of activity in the presence of physiological NaCl concentrations; mutant enzyme is highly inhibited by acetazolamide and shows higher sensitivity to inhibition by anions compared to wild-type; the mutation affects the chloride-mediated negative feedback regulation of the enzyme leading to excessive chloride secretion in sweat; no effect on localization to cell membrane. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 143 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 354 The length of the canonical sequence.
Location on the sequence: help GNPNDPHGSEHTVSGQHFAA E LHIVHYNSDLYPDASTASNK 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         GNPNDPHGSEHTVSGQHFAAELHIVHYNSDLYPDASTASNK

Mouse                         GNRNDPHGSEHTVSGKHFAAELHIVHYNSDLYPDFSTASDK

Rabbit                        GNRNDPYGSEHTVGGKQFAAELHIVHYNSDSYPDISTASNK
Sequence annotation in neighborhood: help 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 25 – 354 Carbonic anhydrase 12
Topological domain 25 – 301 Extracellular
Domain 30 – 289 Alpha-carbonic anhydrase
Binding site 145 – 145
Glycosylation 162 – 162 N-linked (GlcNAc...) asparagine
Disulfide bond 50 – 230
Beta strand 141 – 150



Literature citations
Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.
Lee M.; Vecchio-Pagan B.; Sharma N.; Waheed A.; Li X.; Raraigh K.S.; Robbins S.; Han S.T.; Franca A.L.; Pellicore M.J.; Evans T.A.; Arcara K.M.; Nguyen H.; Luan S.; Belchis D.; Hertecant J.; Zabner J.; Sly W.S.; Cutting G.R.;
Hum. Mol. Genet. 25:1923-1933(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; TISSUE SPECIFICITY; SUBCELLULAR LOCATION; VARIANT HYCHL GLN-121; CHARACTERIZATION OF VARIANTS HYCHL GLN-121 AND LYS-143; Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII.
Feldshtein M.; Elkrinawi S.; Yerushalmi B.; Marcus B.; Vullo D.; Romi H.; Ofir R.; Landau D.; Sivan S.; Supuran C.T.; Birk O.S.;
Am. J. Hum. Genet. 87:713-720(2010)
Cited for: VARIANT HYCHL LYS-143; INVOLVEMENT IN HYCHL; BIOPHYSICOCHEMICAL PROPERTIES; Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of carbonic cnhydrase 12.
Muhammad E.; Leventhal N.; Parvari G.; Hanukoglu A.; Hanukoglu I.; Chalifa-Caspi V.; Feinstein Y.; Weinbrand J.; Jacoby H.; Manor E.; Nagar T.; Beck J.C.; Sheffield V.C.; Hershkovitz E.; Parvari R.;
Hum. Genet. 129:397-405(2011)
Cited for: VARIANT HYCHL LYS-143;
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.