SLC9A8

protein-coding

solute carrier family 9 member A8, the group of Solute carrier family 9

Gene summary

Sodium-hydrogen exchangers (NHEs), such as SLC9A8, are integral transmembrane proteins that exchange extracellular Na+ for intracellular H+. NHEs have multiple functions, including intracellular pH homeostasis, cell volume regulation, and electroneutral NaCl absorption in epithelia (Xu et al., 2008 [PubMed 18209477]).[supplied by OMIM, Apr 2009]

MANE transcript

NM_015266.3

Inheritance

—

ClinVar variants

U:71B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr20:49,812,713-49,892,242

External References & Databases

Ensembl (ENSG00000197818)

Transcript & Mutation Effects

hg38 • Region Span ~79.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC9A8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015266.3. 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			4 clinvar	3 clinvar		7
missense			65 clinvar	2 clinvar		67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	71	5	0	76

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015266.3	RefSeq	NP_056081.1	16	MANE Select
ENST00000361573.3	Ensembl	ENSP00000354966.2	16	MANE Select
NM_001260491.2	RefSeq	NP_001247420.1	16	Standard
ENST00000417961.5	Ensembl	ENSP00000416418.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sodium/Proton exchangers
Transport of inorganic cations/anions and amino acids/oligopeptides
SLC-mediated transmembrane transport
Transport of small molecules

Biological Process

ion transport
sodium ion transmembrane transport
regulation of intracellular pH
potassium ion transmembrane transport
proton transmembrane transport

Molecular Function

sodium:proton antiporter activity
potassium:proton antiporter activity

Cellular Component

Golgi membrane
Golgi apparatus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000417961
Coding exons: 16
Length: 79530
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 59
Defined: 125747
p: 0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.62	266	351	0.757	0.0000201	3927
Missense (PolyPhen)		71	102.37	0.69359		1109
Synonymous	-0.627	150	141	1.07	0.00000938	1155
Loss of Function	1.50	19	27.5	0.691	0.00000125	340

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00027	0.00026	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00028	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00038	0.00036	rare
Other	0.00070	0.00065	rare

dbNSFP Gene Annotations

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. {ECO:0000269|PubMed:15522866}.;

Recessive Scores

pRec: 0.151

Intolerance Scores

LoFtool: 0.811
RVIS EVS: -0.67
RVIS percentile EVS: 15.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.478

Gene Damage Prediction

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