SLC26A3

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

Basic information

Region (hg38): 7:107765467-107803225

Previous symbols: [ "DRA", "CLD" ]

Links

ENSG00000091138 ∙ NCBI:1811 ∙ OMIM:126650 ∙ HGNC:3018 ∙ Uniprot:P40879 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital secretory chloride diarrhea 1 (Strong), mode of inheritance: AR
• congenital secretory chloride diarrhea 1 (Supportive), mode of inheritance: AR
• congenital secretory chloride diarrhea 1 (Definitive), mode of inheritance: AR
• congenital secretory chloride diarrhea 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diarrhea 1, secretory chloride, congenital	AR	Gastrointestinal	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	Gastrointestinal	4162682; 324405; 2651131; 8988888; 11524734; 12442266; 16641574; 17120762; 19861545; 19912155; 19967661; 21332001; 21394828; 21694535; 22277064; 22779076; 23274434

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC26A3 gene.

• not provided (51 variants)
• Congenital secretory diarrhea, chloride type (17 variants)
• SLC26A3-related disorder (1 variants)
• Intestinal obstruction;Hydrops fetalis;Polyhydramnios (1 variants)
• Polyhydramnios;Intestinal obstruction;Hydrops fetalis (1 variants)
• Gastrointestinal obstruction;Hydrops fetalis;Polyhydramnios (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC26A3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	177	5	184
missense	2	4	171	13	5	195
nonsense	20	2				22
start loss	1					1
frameshift	24	2	1			27
inframe indel	2		1			3
splice donor/acceptor (+/-2bp)	4	14				18
splice region	1		11	31	3	46
non coding			9	157	35	201
Total	53	22	184	347	45

Highest pathogenic variant AF is 0.000374

Variants in SLC26A3

This is a list of pathogenic ClinVar variants found in the SLC26A3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-107765469-C-T		Congenital secretory diarrhea, chloride type	Benign (Jan 13, 2018)
7-107765628-T-C		Congenital secretory diarrhea, chloride type	Uncertain significance (Jan 12, 2018)
7-107765650-C-G		Congenital secretory diarrhea, chloride type	Uncertain significance (Jan 13, 2018)
7-107765659-A-G		Congenital secretory diarrhea, chloride type	Uncertain significance (Jan 12, 2018)
7-107765725-G-A		Congenital secretory diarrhea, chloride type	Uncertain significance (Jan 13, 2018)
7-107765742-A-G		Congenital secretory diarrhea, chloride type	Likely benign (Jan 13, 2018)
7-107765861-T-C			Likely benign (Aug 11, 2023)
7-107765871-A-C			Uncertain significance (Aug 23, 2022)
7-107765874-G-A			Uncertain significance (Aug 31, 2021)
7-107765875-G-A			Uncertain significance (Jul 19, 2022)
7-107765876-C-A			Likely benign (Mar 02, 2023)
7-107765880-TG-T		Congenital secretory diarrhea, chloride type	Conflicting classifications of pathogenicity (Nov 17, 2023)
7-107765882-G-A			Likely benign (Feb 17, 2023)
7-107765886-AAGAC-A			Likely benign (Jun 01, 2023)
7-107765890-CAG-C			Likely benign (Jan 25, 2024)
7-107765897-T-C			Likely benign (Oct 09, 2023)
7-107767560-A-G			Likely benign (May 23, 2023)
7-107767562-C-G			Likely benign (Jan 06, 2023)
7-107767565-T-C			Likely benign (Dec 30, 2023)
7-107767566-T-G			Likely benign (Dec 19, 2023)
7-107767587-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2024)
7-107767590-G-A			Uncertain significance (Jul 12, 2022)
7-107767592-T-C		Congenital secretory diarrhea, chloride type	Benign/Likely benign (Jan 31, 2024)
7-107767595-C-T			Uncertain significance (Jul 19, 2022)
7-107767596-G-A			Uncertain significance (Aug 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC26A3	protein_coding	protein_coding	ENST00000340010	20	37759

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.37e-13	0.748	125681	0	67	125748	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.404	387	410	0.944	0.0000224	4976
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000552	0.000551
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00103	0.00103
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.00103	0.00103
South Asian	0.0000980	0.0000980
Other	0.000328	0.000326

dbNSFP

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.
• Pathway: Pancreatic secretion - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Pantoprazole Action Pathway;Rabeprazole Action Pathway;Esomeprazole Action Pathway;Omeprazole Action Pathway;Lansoprazole Action Pathway;Gastric Acid Production;Nizatidine Action Pathway;Cimetidine Action Pathway;Famotidine Action Pathway;Ranitidine Action Pathway;Betazole Action Pathway;Roxatidine acetate Action Pathway;Metiamide Action Pathway;Pirenzepine Action Pathway;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Methionine and cysteine metabolism;Multifunctional anion exchangers (Consensus)

Recessive Scores

• pRec: 0.251

Intolerance Scores

• loftool: 0.157
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.87

Haploinsufficiency Scores

• pHI: 0.354
• hipred: N
• hipred_score: 0.197

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.549

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc26a3
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: slc26a3.1
• Affected structure: excretion
• Phenotype tag: abnormal
• Phenotype quality: decreased magnitude

Gene ontology

• Biological process: regulation of transcription, DNA-templated;ion transport;anion transport;excretion;bicarbonate transport;oxalate transport;sperm capacitation;intracellular pH elevation;membrane hyperpolarization;cellular response to cAMP;sulfate transmembrane transport;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;apical plasma membrane;brush border membrane;sperm midpiece
• Molecular function: DNA-binding transcription factor activity;transcription coregulator activity;transporter activity;inorganic anion exchanger activity;protein binding;secondary active sulfate transmembrane transporter activity;bicarbonate transmembrane transporter activity;chloride transmembrane transporter activity;sulfate transmembrane transporter activity;anion:anion antiporter activity;oxalate transmembrane transporter activity