SLC4A10

Chr 2AR

solute carrier family 4 member 10

Also known as: NBCn2, NCBE

This sodium/bicarbonate cotransporter regulates intracellular pH in neurons, contributes to cerebrospinal fluid secretion, and modulates GABA release and synaptic plasticity. Biallelic mutations cause a neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, inherited in an autosomal recessive pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.375), reflecting its critical role in neuronal pH regulation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.381 OMIM phenotype
Clinical SummarySLC4A10
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ARStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
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ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 118 VUS of 182 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.38LOEUF
pLI 0.134
Z-score 5.38
OE 0.24 (0.160.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.84Z-score
OE missense 0.55 (0.500.60)
312 obs / 569.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.24 (0.160.38)
00.351.4
Missense OE0.55 (0.500.60)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 14 / 58.3Missense obs/exp: 312 / 569.6Syn Z: 0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateSLC4A10-related neurodevelopmental disorder with hypotonia and characteristic brain abnormalitiesLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7035th %ile
GOF
0.7028th %ile
LOF
0.3358th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

182 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic13
VUS118
Likely Benign17
Benign5
25
Pathogenic
13
Likely Pathogenic
118
VUS
17
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
5
19
0
25
Likely Pathogenic
6
1
6
0
13
VUS
4
108
5
1
118
Likely Benign
0
2
1
14
17
Benign
0
1
0
4
5
Total111173119178

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC4A10 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC