NDFIP2

protein-coding

Nedd4 family interacting protein 2

Gene summary

Enables WW domain binding activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in several cellular components, including Golgi apparatus; mitochondrion; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_019080.3

Inheritance

—

ClinVar variants

U:51B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr13:79,481,155-79,556,077

External References & Databases

Ensembl (ENSG00000102471)

Transcript & Mutation Effects

hg38 • Region Span ~74.9 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 NDFIP2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 52

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019080.3. 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			1 clinvar			1
missense			48 clinvar	5 clinvar		53
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	51	5	0	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019080.3	RefSeq	NP_061953.2	7	MANE Select
ENST00000218652.12	Ensembl	ENSP00000218652.7	7	MANE Select
NM_001161407.2	RefSeq	NP_001154879.1	7	Standard
NM_001394685.1	RefSeq	NP_001381614.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

vacuolar transport
negative regulation of gene expression
metal ion transport
positive regulation of protein ubiquitination
negative regulation of transporter activity

Molecular Function

protein binding
WW domain binding

Cellular Component

Golgi membrane
cytoplasm
mitochondrion
endoplasmic reticulum
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000218652
Coding exons: 7
Length: 74924
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125714
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.619	150	173	0.868	0.00000820	2114
Missense (PolyPhen)		22	55.093	0.39932		741
Synonymous	0.0832	69	69.9	0.987	0.00000393	675
Loss of Function	2.88	3	15.1	0.199	6.37e-7	188

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000096	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0.00019	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates HECT domain-containing E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, SMURF2, WWP1 and WWP2, and consequently modulates the stability of their targets. As a result, may control many cellular processes. Recruits ITCH, NEDD4 and SMURF2 to endosomal membranes. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus and multivesicular body where it mediates KCNH2 degradation (PubMed:26363003). May modulate EGFR signaling. Together with NDFIP1, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (By similarity). {ECO:0000250|UniProtKB:Q91ZP6, ECO:0000269|PubMed:12761501, ECO:0000269|PubMed:19343052, ECO:0000269|PubMed:20534535, ECO:0000269|PubMed:26363003}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.420
RVIS EVS: 0.33
RVIS percentile EVS: 73.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.771

Gene Damage Prediction

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