SLC12A9

Chr 7

solute carrier family 12 member 9

Also known as: CCC6, CIP1, WO3.3, hCCC6

NCBI Gene: 56996ENSG00000146828UniProt: Q9BXP2

Predicted to enable potassium:chloride symporter activity. Predicted to be involved in several processes, including chloride ion homeostasis; chloride transmembrane transport; and potassium ion homeostasis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

209
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC12A9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 151 VUS of 209 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 0.85
OE 0.84 (0.61–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.44Z-score
OE missense 0.71 (0.66–0.78)
413 obs / 578.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.84 (0.61–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.66–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 26 / 31.1Missense obs/exp: 413 / 578.1Syn Z: -0.35

ClinVar Variant Classifications

209 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic4
VUS151
Likely Benign22
Benign8
Conflicting1
23
Pathogenic
4
Likely Pathogenic
151
VUS
22
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
19
0
23
Likely Pathogenic
2
0
2
0
4
VUS
0
146
5
0
151
Likely Benign
0
7
9
6
22
Benign
0
0
7
1
8
Conflicting
—1
Total6153427209

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC12A9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC12A9-related syndromic neurodevelopmental disorder with lysosome defects

moderate
ARLoss Of FunctionAltered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
frameshift variantmissense variantstop gained NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biallelic loss-of-function variants of SLC12A9 cause lysosome dysfunction and a syndromic neurodevelopmental disorder.
Accogli A et al.·Genet Med
2024
Clinical value of SLC12A9 for diagnosis and prognosis in colorectal cancer.
Du W et al.·Aging (Albany NY)
2023
Upregulation of SLC12A3 and SLC12A9 Mediated by the HCP5/miR-140-5p Axis Confers Aggressiveness and Unfavorable Prognosis in Uveal Melanoma.
Yan C et al.·Lab Invest
2023
HIST3H2A is a potential biomarker for pancreatic cancer: A study based on TCGA data.
Zhao M et al.·Medicine (Baltimore)
2021
Interactome-transcriptome analysis discovers signatures complementary to GWAS Loci of Type 2 Diabetes.
Li JW et al.·Sci Rep
2016Meta-analysis
Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.
Kong SH et al.·Endocrinol Metab (Seoul)
2024Functional
Genome-wide association analysis identifies multiple loci related to resting heart rate.
Eijgelsheim M et al.·Hum Mol Genet
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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