NHERF2

protein-coding

NHERF family PDZ scaffold protein 2, the group of NHERF family PDZ scaffold proteins|PDZ domain containing

Gene summary

This gene encodes a member of the NHERF family of PDZ scaffolding proteins. These proteins mediate many cellular processes by binding to and regulating the membrane expression and protein-protein interactions of membrane receptors and transport proteins. The encoded protein plays a role in intestinal sodium absorption by regulating the activity of the sodium/hydrogen exchanger 3, and may also regulate the cystic fibrosis transmembrane regulator (CFTR) ion channel. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Previous symbols:

SLC9A3R2

MANE transcript

NM_001130012.3

Inheritance

—

ClinVar variants

U:92B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr16:2,025,356-2,039,026

External References & Databases

Ensembl (ENSG00000065054)

Transcript & Mutation Effects

hg38 • Region Span ~13.7 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 NHERF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001130012.3. 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			3 clinvar	1 clinvar		4
missense			88 clinvar	4 clinvar	2 clinvar	94
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	92	5	2	99

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001130012.3	RefSeq	NP_001123484.1	7	MANE Select
ENST00000424542.7	Ensembl	ENSP00000408005.2	7	MANE Select
NM_001252073.2	RefSeq	NP_001239002.1	6	Standard
NM_001252075.2	RefSeq	NP_001239004.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aldosterone-regulated sodium reabsorption - Homo sapiens (human)
Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
LPA receptor mediated events

Biological Process

protein-containing complex assembly

Molecular Function

signaling receptor binding
protein binding
beta-catenin binding
protein C-terminus binding
phosphatase binding

Cellular Component

nucleus
plasma membrane
focal adhesion
endomembrane system
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000424542
Coding exons: 7
Length: 13671
Individuals with no LoFs: 124167
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124172
p: 0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.174	209	202	1.03	0.0000138	2111
Missense (PolyPhen)		70	79.388	0.88175		898
Synonymous	-0.950	96	84.9	1.13	0.00000592	691
Loss of Function	2.39	5	15.0	0.333	8.94e-7	158

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000068	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000028	0.000027	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus. {ECO:0000269|PubMed:10455146, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:9096337}.;

Recessive Scores

pRec: 0.237

Intolerance Scores

LoFtool: 0.769
RVIS EVS: 0.44
RVIS percentile EVS: 77.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.491

Gene Damage Prediction

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