UniProtKB/SwissProt variant VAR

Carbonic anhydrase 12
Gene: CA12
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Variant information Variant position:

143
Type of variant:

LP/P [Disclaimer]
Residue change:

From Glutamate (E) to Lysine (K) at position 143 (E143K, p.Glu143Lys).
Physico-chemical properties:

Change from medium size and acidic (E) to large size and basic (K)
BLOSUM score:

1
Variant description:

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.
Other resources:

Variant rs267606694 [ dbSNP | Ensembl ]

Sequence information Variant position:

143
Protein sequence length:

354
Location on the sequence:

GNPNDPHGSEHTVSGQHFAA E LHIVHYNSDLYPDASTASNK
Residue conservation:

Human                         GNPNDPHGSEHTVSGQHFAAELHIVHYNSDLYPDASTASNK

Mouse                         GNRNDPHGSEHTVSGKHFAAELHIVHYNSDLYPDFSTASDK

Rabbit                        GNRNDPYGSEHTVGGKQFAAELHIVHYNSDSYPDISTASNK

Sequence annotation in neighborhood:

Type	Positions	Description
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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43570: Variant p.Glu143Lys