SLC9A2

protein-coding

solute carrier family 9 member A2, the group of Solute carrier family 9

Gene summary

This gene encodes a member of the sodium-hydrogen exchanger (NHE) protein family. These proteins are involved in sodium-ion transport by exchanging intracellular hydrogen ions to external sodium ions and help in the regulation of cell pH and volume. The encoded protein is localized to the apical membrane and is involved in apical absorption of sodium. [provided by RefSeq, Jun 2016]

Previous symbols:

NHE2

MANE transcript

NM_003048.6

Inheritance

—

ClinVar variants

U:80B:4

Top phenotype

Mediastinal germ cell tumor

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr2:102,619,553-102,711,355

External References & Databases

Ensembl (ENSG00000115616)

Transcript & Mutation Effects

hg38 • Region Span ~91.8 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 SLC9A2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 79

Mediastinal germ cell tumorTotal: 1

Acute megakaryoblastic leukemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003048.6. 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			1 clinvar	2 clinvar		3
missense			76 clinvar	2 clinvar		78
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	80	4	0	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003048.6	RefSeq	NP_003039.2	12	MANE Select
ENST00000233969.3	Ensembl	ENSP00000233969.2	12	MANE Select
ENST00000907277.1	Ensembl	ENSP00000577336.1	12	Standard
ENST00000907277.2	Ensembl	ENSP00000577336.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

ion transport
protein localization
regulation of intracellular pH
potassium ion transmembrane transport
sodium ion import across plasma membrane

Molecular Function

sodium:proton antiporter activity
potassium:proton antiporter activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000233969
Coding exons: 12
Length: 91612
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.11	331	458	0.722	0.0000253	5291
Missense (PolyPhen)		144	219.66	0.65556		2514
Synonymous	-0.431	192	185	1.04	0.0000108	1642
Loss of Function	3.94	12	38.4	0.313	0.00000256	388

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000066	0.000065	rare
Other	0.00033	0.00033	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. Seems to play an important role in colonic sodium absorption.;

Recessive Scores

pRec: 0.189

Intolerance Scores

LoFtool: 0.594
RVIS EVS: -0.38
RVIS percentile EVS: 28.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.814

Gene Damage Prediction

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