SLC4A10

Chr 2AR

solute carrier family 4 member 10

Also known as: NBCn2, NCBE

NCBI Gene: 57282ENSG00000144290UniProt: Q6U841

This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia and characteristic brain abnormalitiesMIM #620746
AR
183
ClinVar variants
0
Pathogenic / LP
0.13
pLI score
0
Active trials
Clinical Summary— SLC4A10
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
183 total variants — no pathogenic classifications of 183 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
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.
0.38LOEUF
pLI 0.134
Z-score 5.38
OE 0.24 (0.16–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
3.84Z-score
OE missense 0.55 (0.50–0.60)
312 obs / 569.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.24 (0.16–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.50–0.60)
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.0.99
0≤1.21.6
LoF obs/exp: 14 / 58.3Missense obs/exp: 312 / 569.6Syn Z: 0.16

ClinVar Variant Classifications

183 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

SLC4A10 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC4A10-related neurodevelopmental disorder with hypotonia and characteristic brain abnormalities

moderate
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantsplice donor variantframeshift variantmissense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities

MIM #620746

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission.
Fasham J et al.·Brain
2023
Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder.
Maroofian R et al.·Genet Med
2024
NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality.
Böger CA et al.·J Am Soc Nephrol
2017
Poor Collateralization in T2DM: Role of SLC4A10+ MAIT Cells.
Chen S et al.·Arterioscler Thromb Vasc Biol
2025
Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women.
Tam CH et al.·Diabetes Metab J
2025Meta-analysis
Distribution of NBCn2 (SLC4A10) splice variants in mouse brain.
Liu Y et al.·Neuroscience
2010Functional
Bioinformatics identification and validation of maternal blood biomarkers and immune cell infiltration in preeclampsia: An observational study.
Wang H et al.·Medicine (Baltimore)
2024
2q24 deletion in a 9-month old girl with anal atresia, hearing impairment, and hypotonia.
Zhao P et al.·Int J Pediatr Otorhinolaryngol
2018Review
Investigation of the Genetic Etiology in Idiopathic Generalized Epileptic Disorders by Targeted Next-generation Sequencing Technique.
Atlı E et al.·Balkan Med J
2023
Genetic influences on response to mood stabilizers in bipolar disorder: current status of knowledge.
Rybakowski JK·CNS Drugs
2013Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SLC4A10 impedes atherosclerosis by diminishing IFN-γ/GZMB levels of CD8+ T cells via the MAPK pathway.
Chen B et al.·Front Immunol
2025🔓 Open Access
K+-Driven Cl-/HCO3- Exchange Mediated by Slc4a8 and Slc4a10.
Peña-Münzenmayer G et al.·Int J Mol Sci
2024🔓 Open Access
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