SLC10A1

protein-coding

solute carrier family 10 member 1, the group of Solute carrier family 10

Gene summary

The protein encoded by this gene belongs to the sodium/bile acid cotransporter family, which are integral membrane glycoproteins that participate in the enterohepatic circulation of bile acids. Two homologous transporters are involved in the reabsorption of bile acids; the ileal sodium/bile acid cotransporter with an apical cell localization that absorbs bile acids from the intestinal lumen, bile duct and kidney, and the liver-specific sodium/bile acid cotransporter, represented by this protein, that is found in the basolateral membranes of hepatocytes. Bile acids are the catabolic product of cholesterol metabolism, hence this protein is important for cholesterol homeostasis. [provided by RefSeq, Oct 2011]

MANE transcript

NM_003049.4

Inheritance

ClinVar variants

P:30U:131B:32

Top phenotype

hypercholanemia, familial, 2

gnomAD constraint

pLI —, LoF o/e 2.04

Max pathogenic AF

—

Genomic locus

chr14:69,775,416-69,797,241

External References & Databases

Ensembl (ENSG00000100652)

Transcript & Mutation Effects

hg38 • Region Span ~21.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypercholanemia, familial, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0031003

Submitter: PanelApp Australia

hypercholanemia, familial, 2LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0031003

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC10A1 variants in ClinVar

5 Conditions Cataloged

SLC10A1-related disorderTotal: 108

not providedTotal: 82

not specifiedTotal: 64

Hypercholanemia, familial, 2Total: 19

Hepatitis B virus, resistance toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003049.4. 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			10 clinvar	18 clinvar	3 clinvar	31
missense	1 clinvar	2 clinvar	117 clinvar	10 clinvar	1 clinvar	131
nonsense		5 clinvar				5
start loss						0
frameshift	2 clinvar	17 clinvar	3 clinvar			22
splice donor/acceptor (+/-2bp)		3 clinvar	1 clinvar			4
Total	3	27	131	28	4	193

Highest pathogenic variant AF is 0.00022487126

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003049.4	RefSeq	NP_003040.1	5	MANE Select
ENST00000216540.5	Ensembl	ENSP00000216540.4	5	MANE Select
ENST00000871514.1	Ensembl	ENSP00000541573.1	3	Standard
ENST00000871514.2	Ensembl	ENSP00000541573.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bile secretion - Homo sapiens (human)
Drug Induction of Bile Acid Pathway
Farnesoid X Receptor Pathway
Nuclear Receptors Meta-Pathway
Metabolism of lipids

Biological Process

sodium ion transport
bile acid and bile salt transport
viral entry into host cell
transmembrane transport

Molecular Function

virus receptor activity
bile acid:sodium symporter activity

Cellular Component

plasma membrane
integral component of plasma membrane
basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216540
Coding exons: 5
Length: 21873
Individuals with no LoFs: 125519
Homozygous LoFs: 1
Heterozygous LoFs: 228
Defined: 125748
p: 0.000911

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.98	279	200	1.39	0.0000104	2274
Missense (PolyPhen)		92	56.137	1.6388		660
Synonymous	-0.901	86	76.0	1.13	0.00000394	725
Loss of Function	-2.87	18	8.81	2.04	3.68e-7	122

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.0020	0.0020	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00068	0.00068	rare
South Asian	0.0024	0.0023	notable
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium.;

Recessive Scores

pRec: 0.348

Intolerance Scores

LoFtool: 0.990
RVIS EVS: -0.89
RVIS percentile EVS: 10.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.266

Gene Damage Prediction

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