WWP2

WW domain containing E3 ubiquitin protein ligase 2, the group of HECT domain containing|C2 and WW domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 16:69762328-69941741

Links

ENSG00000198373 ∙ NCBI:11060 ∙ OMIM:602308 ∙ HGNC:16804 ∙ Uniprot:O00308 ∙ 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 WWP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WWP2 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					1	1
missense			40		1	41
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	40	0	2

Variants in WWP2

This is a list of pathogenic ClinVar variants found in the WWP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-69787032-C-T		not specified	Uncertain significance (Jun 13, 2023)
16-69798718-C-T		not specified	Uncertain significance (Apr 01, 2024)
16-69798719-T-G			Likely benign (Sep 01, 2024)
16-69798778-C-A		not specified	Uncertain significance (Dec 03, 2021)
16-69798786-C-T		not specified	Uncertain significance (Nov 25, 2024)
16-69798789-A-T		not specified	Uncertain significance (Apr 07, 2023)
16-69798796-G-A		not specified	Uncertain significance (Jul 29, 2023)
16-69799290-G-A		not specified	Uncertain significance (Aug 13, 2021)
16-69840168-A-C		not specified	Uncertain significance (Oct 13, 2021)
16-69840175-C-A		not specified	Uncertain significance (Mar 20, 2024)
16-69840187-C-T			Likely benign (Nov 01, 2024)
16-69840200-A-G		not specified	Uncertain significance (Feb 13, 2023)
16-69840209-G-C		not specified	Uncertain significance (Nov 16, 2024)
16-69840225-A-G		not specified	Uncertain significance (Feb 22, 2023)
16-69840261-A-C		not specified	Uncertain significance (Sep 17, 2021)
16-69842024-G-A		not specified	Uncertain significance (Sep 10, 2024)
16-69842059-G-C		not specified	Uncertain significance (Oct 05, 2021)
16-69842080-C-T		not specified	Uncertain significance (Dec 07, 2024)
16-69842088-C-T			Benign (Dec 15, 2018)
16-69842096-C-G		not specified	Uncertain significance (Dec 07, 2024)
16-69842105-T-A		not specified	Uncertain significance (Aug 21, 2023)
16-69842119-C-T		not specified	Uncertain significance (Jul 09, 2024)
16-69871818-C-G		not specified	Uncertain significance (Oct 25, 2022)
16-69871818-C-T			Benign (Apr 30, 2018)
16-69888043-T-A		not specified	Uncertain significance (Mar 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WWP2	protein_coding	protein_coding	ENST00000359154	23	179436

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.165	0.835	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.59	454	560	0.810	0.0000362	5677
Missense in Polyphen		187	285.12	0.65587		2832
Synonymous	0.591	211	222	0.950	0.0000151	1670
Loss of Function	5.21	13	54.5	0.238	0.00000272	576

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000174	0.000174
Ashkenazi Jewish	0.00	0.00
East Asian	0.00289	0.00289
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000887	0.0000879
Middle Eastern	0.00289	0.00289
South Asian	0.0000327	0.0000327
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation- induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation. {ECO:0000269|PubMed:19274063, ECO:0000269|PubMed:19651900}.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Signal Transduction;Regulation of PTEN stability and activity;NOTCH3 Activation and Transmission of Signal to the Nucleus;Signaling by NOTCH3;Signaling by NOTCH;PTEN Regulation;PIP3 activates AKT signaling;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.366
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.8

Haploinsufficiency Scores

• pHI: 0.761
• hipred: Y
• hipred_score: 0.793
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wwp2
• Phenotype: skeleton phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: wwp2
• Affected structure: palate
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;protein polyubiquitination;cellular protein modification process;ubiquitin-dependent protein catabolic process;extracellular transport;negative regulation of gene expression;protein ubiquitination;negative regulation of transporter activity;regulation of ion transmembrane transport;regulation of membrane potential;proteasome-mediated ubiquitin-dependent protein catabolic process;negative regulation of DNA-binding transcription factor activity;positive regulation of protein catabolic process;negative regulation of Notch signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;viral entry into host cell;negative regulation of protein transport;protein autoubiquitination;protein K63-linked ubiquitination;regulation of potassium ion transmembrane transporter activity
• Cellular component: ubiquitin ligase complex;nucleus;cytoplasm;cytosol;membrane;extracellular exosome
• Molecular function: RNA polymerase II transcription factor binding;ubiquitin-protein transferase activity;protein binding;transcription factor binding;ubiquitin protein ligase activity