SLC10A2

Chr 13AR

solute carrier family 10 member 2

Also known as: ASBT, IBAT, ISBT, NTCP2, PBAM, PBAM1

This protein is a sodium/bile acid cotransporter that mediates reabsorption of bile acids in the distal ileum and renal proximal tubules, playing a critical role in enterohepatic circulation and cholesterol homeostasis. Mutations cause primary bile acid malabsorption, an autosomal recessive disorder affecting the gastrointestinal system. The gene shows high tolerance to loss-of-function variants (LOEUF 1.944), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.941 OMIM phenotype
Clinical SummarySLC10A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.94LOEUF
pLI 0.000
Z-score -2.02
OE 1.62 (1.111.94)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.20Z-score
OE missense 1.43 (1.301.58)
292 obs / 203.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.62 (1.111.94)
00.351.4
Missense OE1.43 (1.301.58)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 20 / 12.4Missense obs/exp: 292 / 203.5Syn Z: -0.98
DN
0.74top 25%
GOF
0.79top 25%
LOF
0.2191th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC10A2 · 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.

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Clinical Literature
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