SLC9A3

solute carrier family 9 member A3, the group of Solute carrier family 9

Basic information

Region (hg38): 5:470455-524449

Previous symbols: [ "NHE3" ]

Links

ENSG00000066230 ∙ NCBI:6550 ∙ OMIM:182307 ∙ HGNC:11073 ∙ Uniprot:P48764 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital secretory sodium diarrhea 8 (Strong), mode of inheritance: AR
• congenital secretory sodium diarrhea 8 (Moderate), mode of inheritance: AR
• congenital secretory sodium diarrhea 8 (Strong), mode of inheritance: AR
• congenital sodium diarrhea (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diarrhea 8, secretory sodium, congenital	AR	Gastrointestinal	Individuals have been described with severe, early-onset diarrhea and related electrolyte imbalances, and awareness may allow prompt and appropriate management of nutrition and fluid balance	Gastrointestinal	3880821; 26358773; 30633106; 31276831

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC9A3 gene.

• not provided (531 variants)
• Inborn genetic diseases (21 variants)
• Congenital secretory sodium diarrhea 8 (17 variants)
• Autism spectrum disorder (1 variants)
• SLC9A3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC9A3 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			1	165	22	188
missense	1	1	177	7	5	191
nonsense	1					1
start loss			1			1
frameshift	2					2
inframe indel			6			6
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			8	26	3	37
non coding				92	18	110
Total	5	4	186	264	45

Highest pathogenic variant AF is 0.00000657

Variants in SLC9A3

This is a list of pathogenic ClinVar variants found in the SLC9A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-473144-C-A			Likely benign (Aug 01, 2023)
5-473291-C-G			Benign (Aug 01, 2023)
5-473382-C-G			Uncertain significance (May 12, 2021)
5-473387-G-A			Likely benign (Aug 04, 2023)
5-473389-G-A			Likely benign (Jul 30, 2023)
5-473394-G-A			Likely benign (Jan 23, 2023)
5-473397-G-A			Likely benign (Oct 20, 2023)
5-473400-G-A			Likely benign (Dec 13, 2023)
5-474862-C-T			Likely benign (Jul 31, 2023)
5-474867-G-A			Likely benign (Aug 30, 2022)
5-474868-G-A			Likely benign (Nov 01, 2022)
5-474869-C-T			Likely benign (Jan 24, 2023)
5-474872-G-A			Likely benign (Sep 01, 2022)
5-474872-G-C			Likely benign (Jun 07, 2023)
5-474893-A-G			Uncertain significance (Apr 29, 2022)
5-474897-G-C			Likely benign (Oct 13, 2023)
5-474900-G-C			Likely benign (Jan 19, 2024)
5-474904-G-T			Uncertain significance (Dec 30, 2021)
5-474914-G-T			Uncertain significance (Oct 05, 2022)
5-474915-C-T			Likely benign (Feb 18, 2022)
5-474920-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
5-474924-G-C			Likely benign (Jun 20, 2023)
5-474945-G-A			Likely benign (Sep 10, 2023)
5-474957-C-G			Uncertain significance (Aug 16, 2021)
5-474961-C-T			Uncertain significance (Mar 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC9A3	protein_coding	protein_coding	ENST00000264938	17	51023

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.978	0.0215	125698	0	10	125708	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.49	365	526	0.694	0.0000349	5322
Missense in Polyphen		105	213.81	0.49109		2034
Synonymous	-2.05	288	247	1.17	0.0000188	1731
Loss of Function	4.83	6	38.2	0.157	0.00000216	393

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000620	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.0000504	0.0000462
European (Non-Finnish)	0.0000548	0.0000528
Middle Eastern	0.0000547	0.0000544
South Asian	0.0000354	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient (PubMed:26358773). Plays an important role in signal transduction. {ECO:0000269|PubMed:26358773}.
• Disease: DISEASE: Diarrhea 8, secretory sodium, congenital (DIAR8) [MIM:616868]: A disease characterized by watery secretory diarrhea with prenatal onset, prominent abdominal distension after birth due to dilated fluid-filled loops of intestine, elevated fecal sodium concentrations and low urinary sodium concentrations. {ECO:0000269|PubMed:26358773}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Bile secretion - Homo sapiens (human);Proximal tubule bicarbonate reclamation - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Sodium/Proton exchangers;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Gastrin;Endothelins;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.0991

Intolerance Scores

• loftool: 0.169
• rvis_EVS: -1.79
• rvis_percentile_EVS: 2.26

Haploinsufficiency Scores

• pHI: 0.130
• hipred: Y
• hipred_score: 0.759
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.686

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc9a3
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; digestive/alimentary phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: slc9a3.2
• Affected structure: NCC ionocyte
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: ion transport;regulation of intracellular pH;potassium ion transmembrane transport;sodium ion import across plasma membrane;proton transmembrane transport
• Cellular component: plasma membrane;brush border;cell surface;integral component of membrane;apical plasma membrane;brush border membrane;extracellular exosome
• Molecular function: protein binding;sodium:proton antiporter activity;potassium:proton antiporter activity;PDZ domain binding