SLC26A3

protein-coding

solute carrier family 26 member 3, the group of Solute carrier family 26

Gene summary

The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]

Previous symbols:

MANE transcript

NM_000111.3

Inheritance

ClinVar variants

P:130U:229B:245

Top phenotype

Diarrhea 1, secretory chloride, congenital

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr7:107,765,467-107,803,225

External References & Databases

Ensembl (ENSG00000091138)

Transcript & Mutation Effects

hg38 • Region Span ~37.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital secretory chloride diarrhea 1SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008964

Submitter: Orphanet

congenital secretory chloride diarrhea 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008964

Submitter: PanelApp Australia

congenital secretory chloride diarrhea 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008964

Submitter: Labcorp Genetics (formerly Invitae)

congenital secretory chloride diarrhea 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008964

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Diarrhea 1, secretory chloride, congenitalAR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: Due to copious high-chloride diarrhea individuals may manifest with with dehydration and electrolyte imbalances such as hypokalemia, and metabolic alkalosis, and recognition can allow monitoring of electrolyte and hydration status and appropriate supportive therapy with oral intake of chloride, sodium, and potassium to ensure an appropriate electrolyte balance, as well as medications such as omeprazole to reduce fecal electrolyte output

Refs: 4162682; 324405; 2651131; 8988888; 11524734; 12442266; 16641574; 17120762; 19861545; 19912155; 19967661; 21332001; 21394828; 21694535; 22277064; 22779076; 23274434

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC26A3 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 723

Congenital secretory diarrhea, chloride typeTotal: 150

Inborn genetic diseasesTotal: 101

not specifiedTotal: 36

SLC26A3-related disorderTotal: 31

PolyhydramniosTotal: 3

Hydrops fetalisTotal: 3

Intestinal obstructionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000111.3. 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			7 clinvar	218 clinvar	1 clinvar	226
missense	3 clinvar	24 clinvar	221 clinvar	23 clinvar	3 clinvar	274
nonsense	20 clinvar	9 clinvar				29
start loss		1 clinvar				1
frameshift	26 clinvar	21 clinvar	1 clinvar			48
splice donor/acceptor (+/-2bp)	7 clinvar	19 clinvar				26
Total	56	74	229	241	4	604

Highest pathogenic variant AF is 0.00020446655

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000111.3	RefSeq	NP_000102.1	20	MANE Select
ENST00000340010.10	Ensembl	ENSP00000345873.5	20	MANE Select
ENST00000379083.7	Ensembl	ENSP00000368375.3	2	Standard
ENST00000453332.1	Ensembl	ENSP00000395955.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
slc26a3.1	Danio rerio	Structure: excretion Quality: decreased magnitude abnormal

Gene / Model

Organism

Observed Phenotype

slc26a3.1

Danio rerio

Structure: excretion

Quality: decreased magnitude

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pancreatic secretion - Homo sapiens (human)
Mineral absorption - Homo sapiens (human)
Pantoprazole Action Pathway
Rabeprazole Action Pathway
Esomeprazole Action Pathway

Biological Process

regulation of transcription, DNA-templated
ion transport
anion transport
excretion
bicarbonate transport

Molecular Function

DNA-binding transcription factor activity
transcription coregulator activity
transporter activity
inorganic anion exchanger activity
protein binding

Cellular Component

plasma membrane
integral component of plasma membrane
membrane
apical plasma membrane
brush border membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340010
Coding exons: 20
Length: 37759
Individuals with no LoFs: 125681
Homozygous LoFs: 0
Heterozygous LoFs: 67
Defined: 125748
p: 0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.404	387	410	0.944	0.0000224	4976
Missense (PolyPhen)		127	166.09	0.76464		2128
Synonymous	0.0795	152	153	0.992	0.00000885	1531
Loss of Function	1.78	26	37.8	0.688	0.00000187	474

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0010	0.0010	notable
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Chloride/bicarbonate exchanger. Mediates the efficient absorption of chloride ions in the colon, participating in fluid homeostasis. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.;
Disease: DISEASE: Diarrhea 1, secretory chloride, congenital (DIAR1) [MIM:214700]: A disease characterized by voluminous watery stools containing an excess of chloride. The children with this disease are often premature. {ECO:0000269|PubMed:11524734, ECO:0000269|PubMed:19861545, ECO:0000269|PubMed:21150650, ECO:0000269|PubMed:21394828, ECO:0000269|PubMed:22779076, ECO:0000269|PubMed:23274434, ECO:0000269|PubMed:28644346, ECO:0000269|PubMed:8896562, ECO:0000269|PubMed:9554749, ECO:0000269|PubMed:9718329}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.251

Intolerance Scores

LoFtool: 0.157
RVIS EVS: 0.6
RVIS percentile EVS: 82.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.549

Gene Damage Prediction

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