SLC12A5

Chr 20

solute carrier family 12 member 5

Also known as: DEE34, EIEE34, EIG14, KCC2, hKCC2

NCBI Gene: 57468ENSG00000124140UniProt: Q9H2X9

K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 34
UniProtEpilepsy, idiopathic generalized 14

Clinical highlights

Gene-disease validity (ClinGen)
genetic developmental and epileptic encephalopathy · ARLimitednot for standalone diagnostic reporting
Interpreting a novel variant
Loss of function is the established mechanism and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
23
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.14
LOEUF· LoF intol.
LOF
Mechanism· annotated
📖
GeneReview available — SLC12A5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.14LOEUF
pLI 1.000
Z-score 6.58
OE 0.05 (0.02–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.70Z-score
OE missense 0.50 (0.46–0.55)
347 obs / 696.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.05 (0.02–0.14)
0≤0.351.4
Missense OE?0.50 (0.46–0.55)
0≤0.61.4
Synonymous OE?0.92
0≤1.21.6
LoF obs/exp: 3 / 56.3Missense obs/exp: 347 / 696.1Syn Z: 1.01

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SLC12A5 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients