SLC10A2

protein-coding

solute carrier family 10 member 2, the group of Solute carrier family 10

Gene summary

This gene encodes a sodium/bile acid cotransporter. This transporter is the primary mechanism for uptake of intestinal bile acids by apical cells in the distal ileum. Bile acids are the catabolic product of cholesterol metabolism, so this protein is also critical for cholesterol homeostasis. Mutations in this gene cause primary bile acid malabsorption (PBAM); muatations in this gene may also be associated with other diseases of the liver and intestines, such as familial hypertriglyceridemia (FHTG). [provided by RefSeq, Mar 2010]

Previous symbols:

ASBT
ISBT

MANE transcript

NM_000452.3

Inheritance

AR, AD

ClinVar variants

P:5U:262B:104

Top phenotype

Bile acid malabsorption, primary 1

gnomAD constraint

pLI —, LoF o/e 1.62

Max pathogenic AF

—

Genomic locus

chr13:103,043,998-103,066,417

External References & Databases

Ensembl (ENSG00000125255)

Transcript & Mutation Effects

hg38 • Region Span ~22.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

bile acid malabsorption, primary, 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013214

Submitter: Labcorp Genetics (formerly Invitae)

bile acid malabsorption, primary, 1LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013214

Submitter: PanelApp Australia

bile acid malabsorption, primary, 1LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013214

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Bile acid malabsorption, primary 1AD

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: Individuals may present with manifestations of diarrhea/steatorrhea such as anasarca and nutritional deficiencies due to fecal loss, and dietary and medical interventions (eg, medium chain triglycerides, bile acid sequestrants) may be beneficial

Refs: 1017717; 430290; 7106511; 9109432; 9109422; 19823678; 21649730

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC10A2 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 371

SLC10A2-related disorderTotal: 99

not specifiedTotal: 85

Bile acid malabsorption, primary, 1Total: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000452.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	87 clinvar	2 clinvar	91
missense			223 clinvar	14 clinvar	1 clinvar	238
nonsense		1 clinvar	13 clinvar			14
start loss			2 clinvar			2
frameshift		2 clinvar	12 clinvar			14
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	10 clinvar			12
Total	1	4	262	101	3	371

Highest pathogenic variant AF is 0.0000980498

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000452.3	RefSeq	NP_000443.2	6	MANE Select
ENST00000245312.5	Ensembl	ENSP00000245312.3	6	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bile secretion - Homo sapiens (human)
Metabolism of lipids
Metabolism
Recycling of bile acids and salts
Bile acid and bile salt metabolism

Biological Process

sodium ion transport
response to bacterium
bile acid and bile salt transport
transmembrane transport

Molecular Function

bile acid:sodium symporter activity

Cellular Component

plasma membrane
integral component of plasma membrane
microvillus
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000245312
Coding exons: 6
Length: 22847
Individuals with no LoFs: 125558
Homozygous LoFs: 0
Heterozygous LoFs: 190
Defined: 125748
p: 0.000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.20	292	204	1.43	0.0000116	2266
Missense (PolyPhen)		80	50.473	1.585		550
Synonymous	-0.982	98	86.4	1.13	0.00000623	708
Loss of Function	-2.02	20	12.4	1.62	6.15e-7	137

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00081	0.00081	rare
Ashkenazi Jewish	0.00079	0.00079	rare
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00082	0.00082	rare
South Asian	0.0015	0.0015	notable
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.;
Disease: DISEASE: Primary bile acid malabsorption (PBAM) [MIM:613291]: An intestinal disorder associated with chronic watery diarrhea, excess fecal bile acids, steatorrhea and interruption of the enterohepatic circulation of bile acids. {ECO:0000269|PubMed:9109432}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.320

Intolerance Scores

LoFtool: 0.966
RVIS EVS: -0.11
RVIS percentile EVS: 45.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.767

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium