SLC9A4

solute carrier family 9 member A4, the group of Solute carrier family 9

Basic information

Region (hg38): 2:102473225-102533972

Links

ENSG00000180251 ∙ NCBI:389015 ∙ OMIM:600531 ∙ HGNC:11077 ∙ Uniprot:Q6AI14 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC9A4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC9A4 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						0
missense			46	2	1	49
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	46	2	1

Variants in SLC9A4

This is a list of pathogenic ClinVar variants found in the SLC9A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-102473800-G-A		not specified	Uncertain significance (Jan 10, 2022)
2-102473809-T-C			Benign (Jun 13, 2018)
2-102473836-C-T		not specified	Uncertain significance (Oct 14, 2023)
2-102473868-A-G		not specified	Uncertain significance (Jul 09, 2021)
2-102473889-G-A		not specified	Uncertain significance (Apr 01, 2024)
2-102473916-C-T		not specified	Uncertain significance (Feb 05, 2024)
2-102473928-A-G		not specified	Uncertain significance (Dec 01, 2022)
2-102473971-A-C		not specified	Uncertain significance (Oct 26, 2022)
2-102474013-T-C		not specified	Uncertain significance (Mar 01, 2024)
2-102476054-C-T		Ascending aortic dissection	association (Feb 01, 2021)
2-102478941-A-C		not specified	Uncertain significance (Aug 28, 2021)
2-102478945-G-A		Ascending aortic dissection	association (Feb 01, 2021)
2-102479033-T-C		not specified	Uncertain significance (Jul 12, 2022)
2-102479058-T-G		not specified	Uncertain significance (Jul 05, 2023)
2-102479070-T-C		not specified	Uncertain significance (Mar 25, 2022)
2-102479079-C-A		not specified	Uncertain significance (Mar 31, 2024)
2-102479128-G-C		not specified	Uncertain significance (Oct 25, 2023)
2-102479210-G-A		not specified	Uncertain significance (Nov 15, 2021)
2-102479241-T-C		not specified	Uncertain significance (Jun 16, 2024)
2-102479258-A-G		not specified	Uncertain significance (Jun 18, 2021)
2-102479286-A-G		not specified	Uncertain significance (Feb 10, 2022)
2-102479289-A-T		not specified	Uncertain significance (Jul 12, 2022)
2-102503455-A-G		not specified	Uncertain significance (May 22, 2024)
2-102503536-T-C		not specified	Uncertain significance (Sep 16, 2021)
2-102503541-G-A		not specified	Likely benign (May 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC9A4	protein_coding	protein_coding	ENST00000295269	12	60670

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.29e-14	0.236	125619	1	128	125748	0.000513

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.611	492	455	1.08	0.0000250	5245
Missense in Polyphen		192	185.54	1.0348		2206
Synonymous	-0.667	191	180	1.06	0.0000110	1559
Loss of Function	1.12	24	30.7	0.782	0.00000155	360

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00386	0.00386
Ashkenazi Jewish	0.00	0.00
East Asian	0.000654	0.000653
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000317	0.000308
Middle Eastern	0.000654	0.000653
South Asian	0.000393	0.000327
Other	0.000165	0.000163

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. Plays an important role in signal transduction. May play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage. Is relatively amiloride and ethylisopropylamiloride (EIPA) insensitive. Can be activated under conditions of hyperosmolar-induced cell shrinkage in a sustained intracellular acidification-dependence manner. Activated by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a sustained intracellular acidification-dependence manner. Affects potassium/proton exchange as well as sodium/proton and lithium/proton exchange. In basolateral cell membrane, participates in homeostatic control of intracellular pH, and may play a role in proton extrusion in order to achieve transepithelial HCO3(-) secretion. In apical cell membrane may be involved in mediating sodium absorption. Requires for normal levels of gastric acid secretion, secretory membrane development, parietal cell maturation and/or differentiation and at least secondarily for chief cell differentiation (By similarity). {ECO:0000250}.
• Pathway: Gastric acid secretion - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Sodium/Proton exchangers;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.911
• rvis_EVS: 0.85
• rvis_percentile_EVS: 88.49

Haploinsufficiency Scores

• pHI: 0.140
• hipred: N
• hipred_score: 0.231

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.818

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc9a4
• Phenotype: immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: gastric acid secretion;epithelial cell development;ion transport;regulation of intracellular pH;potassium ion transmembrane transport;sodium ion import across plasma membrane;proton transmembrane transport
• Cellular component: plasma membrane;integral component of membrane;basolateral plasma membrane;apical plasma membrane
• Molecular function: sodium:proton antiporter activity;potassium:proton antiporter activity