SLC4A10

Chr 2AR

solute carrier family 4 member 10

Also known as: NBCn2, NCBE

NCBI Gene: 57282 ENSG00000144290 UniProt: Q6U841 OMIM: 605556

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.381 OMIM phenotype

Clinical Summary— SLC4A10

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ARStrong

Strong evidence — appropriate for clinical testing

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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

15 unique Pathogenic / Likely Pathogenic· 114 VUS of 156 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

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?

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?

LoF OE?0.24 (0.16–0.38)

0≤0.351.4

Missense OE?0.55 (0.50–0.60)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

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

This gene — mechanism propensity

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

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic8

VUS114

Likely Benign18

Benign5

Pathogenic

Likely Pathogenic

114

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	5	1	0	7
Likely Pathogenic	6	1	1	0	8
VUS	4	108	1	1	114
Likely Benign	0	2	2	14	18
Benign	0	1	0	4	5
Total	11	117	5	19	152

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap SLC4A10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →