UniProtKB/Swiss-Prot P55017: Variant p.Gly741Arg

Solute carrier family 12 member 3
Gene: SLC12A3
Chromosomal location: 16q13
Variant information

Variant position:  741
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 741 (G741R, p.Gly741Arg).
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:  Gitelman syndrome (GTLMNS) [MIM:263800]: An autosomal recessive disorder characterized by hypokalemic alkalosis in combination with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. Patients are often asymptomatic or present transient periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. The phenotype is highly heterogeneous in terms of age at onset and severity. Cardinal features such as hypocalciuria and hypomagnesemia might also change during the life cycle of a given patient. It has overlapping features with Bartter syndrome. {ECO:0000269|PubMed:10616841, ECO:0000269|PubMed:10988270, ECO:0000269|PubMed:11168953, ECO:0000269|PubMed:11940055, ECO:0000269|PubMed:12008755, ECO:0000269|PubMed:12112667, ECO:0000269|PubMed:15069170, ECO:0000269|PubMed:15687331, ECO:0000269|PubMed:16429844, ECO:0000269|PubMed:17654016, ECO:0000269|PubMed:17873326, ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:26099046, ECO:0000269|PubMed:8528245, ECO:0000269|PubMed:8900229, ECO:0000269|PubMed:8954067, ECO:0000269|PubMed:9734597}. 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 GTLMNS.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  741
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1021
The length of the canonical sequence.

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.




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.

Chain 1 – 1021 Solute carrier family 12 member 3
Topological domain 682 – 1021 Cytoplasmic

Literature citations

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.
Simon D.B.; Nelson-Williams C.; Bia M.J.; Ellison D.; Karet F.E.; Molina A.M.; Vaara I.; Iwata F.; Cushner H.M.; Koolen M.; Gainza F.J.; Gitelman H.J.; Lifton R.P.;
Nat. Genet. 12:24-30(1996)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); VARIANTS GTLMNS TRP-209; GLY-264; LEU-349; ARG-421; ASN-486; CYS-496; SER-561 DEL; VAL-588; VAL-630; HIS-655; LEU-655; ARG-741; PRO-850 AND GLN-955; VARIANT THR-728; FUNCTION;

Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain.
Lemmink H.H.; Knoers N.V.A.M.; Karolyi L.; van Dijk H.; Niaudet P.; Antignac C.; Guay-Woodford L.M.; Goodyer P.R.; Carel J.-C.; Hermes A.; Seyberth H.W.; Monnens L.A.H.; van den Heuvel L.P.W.J.;
Kidney Int. 54:720-730(1998)
Cited for: VARIANTS GTLMNS TRP-209; PRO-215; THR-226; HIS-261; HIS-560; SER-613; HIS-642; ARG-649; CYS-655; ARG-738; ARG-741; PRO-850 AND CYS-852; VARIANTS GLN-904 AND CYS-919;

Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension.
Melander O.; Orho-Melander M.; Bengtsson K.; Lindblad U.; Rastam L.; Groop L.; Hulthen U.L.;
Hypertension 36:389-394(2000)
Cited for: VARIANTS GTLMNS PRO-304; SER-439; ARG-731 AND ARG-741; VARIANT GLN-904;

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome.
Glaudemans B.; Yntema H.G.; San-Cristobal P.; Schoots J.; Pfundt R.; Kamsteeg E.J.; Bindels R.J.; Knoers N.V.; Hoenderop J.G.; Hoefsloot L.H.;
Eur. J. Hum. Genet. 20:263-270(2012)
Cited for: VARIANTS GTLMNS MET-60; HIS-62; GLN-83; TRP-83; ASP-121; CYS-135; CYS-145; MET-150; MET-153; PRO-157; LEU-158; MET-163; VAL-166; ARG-172; LEU-178; THR-192; ILE-194; GLN-209; ARG-235; ASN-259; PRO-272; MET-304; PRO-304; VAL-313; TRP-321; TRP-334; GLU-374; MET-382; ILE-392; CYS-399; 433-GLN--CYS-436 DELINS LEU; SER-439; SER-442; ARG-463; THR-464; CYS-475; HIS-489; CYS-507; THR-523; SER-534; LEU-536; GLY-546; LEU-555; ARG-560; ASN-566 DEL; LEU-615; CYS-642; CYS-642; GLY-642; HIS-642; LEU-643; MET-647; HIS-655; LYS-ALA-PHE-TYR-SER-ASP-VAL-ILE-713 INS; VAL-729; ARG-735; ARG-741; LEU-751; THR-824; ASN-839; PHE-849; PRO-850; CYS-852; CYS-862; THR-872; GLN-887; TRP-934; TRP-935; GLN-955; GLY-958; ARG-980; TYR-985; GLN-1009 AND ARG-1021; CHARACTERIZATION OF VARIANT GTLMNS ASP-121; ILE-392; SER-442; CYS-475; HIS-489; LEU-751 AND ARG-1021; FUNCTION; SUBCELLULAR LOCATION;

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.