NDFIP2

Nedd4 family interacting protein 2

Basic information

Region (hg38): 13:79481154-79556077

Links

ENSG00000102471 ∙ NCBI:54602 ∙ OMIM:610041 ∙ HGNC:18537 ∙ Uniprot:Q9NV92 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDFIP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDFIP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			21	3		24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	21	3	0

Variants in NDFIP2

This is a list of pathogenic ClinVar variants found in the NDFIP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-79481214-G-A		not specified	Uncertain significance (Dec 06, 2021)
13-79481219-A-T		not specified	Uncertain significance (Mar 31, 2022)
13-79481268-G-A		not specified	Uncertain significance (Nov 29, 2023)
13-79481276-G-A		not specified	Uncertain significance (Jan 31, 2024)
13-79481277-A-G		not specified	Uncertain significance (May 23, 2023)
13-79481288-G-C		not specified	Likely benign (Aug 12, 2021)
13-79481289-G-A		not specified	Uncertain significance (May 16, 2023)
13-79481301-A-C		not specified	Uncertain significance (Aug 26, 2022)
13-79481319-C-T		not specified	Uncertain significance (Dec 07, 2021)
13-79481328-G-C		not specified	Uncertain significance (Mar 30, 2022)
13-79481334-C-A		not specified	Uncertain significance (Aug 15, 2023)
13-79481411-T-G		not specified	Uncertain significance (Dec 08, 2021)
13-79481427-T-C		not specified	Uncertain significance (Sep 01, 2021)
13-79481472-C-G		not specified	Uncertain significance (May 07, 2024)
13-79481507-A-C		not specified	Uncertain significance (Apr 27, 2022)
13-79520846-A-G		not specified	Likely benign (Jan 10, 2022)
13-79520876-C-T		not specified	Uncertain significance (Jun 21, 2021)
13-79520877-C-T		not specified	Uncertain significance (Oct 27, 2021)
13-79520898-C-A		not specified	Uncertain significance (Jan 09, 2024)
13-79533337-G-A		not specified	Likely benign (Feb 10, 2022)
13-79533377-C-T		not specified	Uncertain significance (Jan 23, 2023)
13-79533424-A-G		not specified	Uncertain significance (Sep 20, 2023)
13-79543572-A-C		not specified	Uncertain significance (Apr 19, 2023)
13-79548388-G-A		not specified	Uncertain significance (Apr 25, 2022)
13-79548391-C-G		not specified	Uncertain significance (Mar 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDFIP2	protein_coding	protein_coding	ENST00000218652	7	74924

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.527	0.472	125710	0	4	125714	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.619	150	173	0.868	0.00000820	2114
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000955	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000334	0.0000327
Other	0.000194	0.000163

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.145
• hipred: Y
• hipred_score: 0.804
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.771

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndfip2
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype

Gene ontology

• Biological process: vacuolar transport;negative regulation of gene expression;metal ion transport;positive regulation of protein ubiquitination;negative regulation of transporter activity;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of protein transport
• Cellular component: Golgi membrane;cytoplasm;mitochondrion;endoplasmic reticulum;Golgi apparatus;integral component of membrane;multivesicular body membrane;intracellular membrane-bounded organelle;perinuclear region of cytoplasm
• Molecular function: protein binding;WW domain binding