CNKSR3

protein-coding

CNKSR family member 3, the group of PDZ domain containing|Sterile alpha motif domain containing

Gene summary

Predicted to enable protein-macromolecule adaptor activity. Predicted to be involved in several processes, including negative regulation of ERK1 and ERK2 cascade; negative regulation of peptidyl-serine phosphorylation; and positive regulation of sodium ion transport. Predicted to act upstream of or within positive regulation of sodium ion transmembrane transporter activity. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

MAGI1

MANE transcript

NM_173515.4

Inheritance

—

ClinVar variants

U:82B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr6:154,387,515-154,510,685

External References & Databases

Ensembl (ENSG00000153721)

Transcript & Mutation Effects

hg38 • Region Span ~123.2 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 CNKSR3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173515.4. 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		2 clinvar	6
missense			76 clinvar	2 clinvar		78
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	82	2	2	86

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173515.4	RefSeq	NP_775786.2	13	MANE Select
ENST00000607772.6	Ensembl	ENSP00000475915.1	13	MANE Select
NM_001368116.1	RefSeq	NP_001355045.1	13	Standard
NM_001368117.1	RefSeq	NP_001355046.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of sodium ion transport
negative regulation of peptidyl-serine phosphorylation
negative regulation of ERK1 and ERK2 cascade
positive regulation of sodium ion transmembrane transporter activity

Molecular Function

protein binding

Cellular Component

cytoplasm
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000607772
Coding exons: 13
Length: 123156
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125747
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.585	301	331	0.909	0.0000199	3576
Missense (PolyPhen)		111	133.37	0.83225		1418
Synonymous	0.965	120	134	0.894	0.00000837	1109
Loss of Function	3.74	9	31.8	0.283	0.00000187	346

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00023	0.00023	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in transepithelial sodium transport. Regulates aldosterone-induced and epithelial sodium channel (ENaC)-mediated sodium transport through regulation of ENaC cell surface expression. Acts as a scaffold protein coordinating the assembly of an ENaC-regulatory complex (ERC). {ECO:0000269|PubMed:22851176}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.619
RVIS EVS: -0.02
RVIS percentile EVS: 52.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.141

Gene Damage Prediction

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