SLC12A3

Chr 16

solute carrier family 12 member 3

Also known as: NCC, NCCT, TSC

This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGitelman syndrome
1
Active trials
62
Pubs (1 yr)
P/LP submissions
P/LP missense
1.20
LOEUF
Multiple*
Mechanism· predicted
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GeneReview available — SLC12A3
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.20LOEUF
pLI 0.000
Z-score 0.36
OE 0.95 (0.751.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.94Z-score
OE missense 1.11 (1.041.18)
682 obs / 616.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.95 (0.751.20)
00.351.4
Missense OE?1.11 (1.041.18)
00.61.4
Synonymous OE?1.09
01.21.6
LoF obs/exp: 50 / 52.8Missense obs/exp: 682 / 616.6Syn Z: -1.08

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC12A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.