WBP2

WW domain binding protein 2, the group of GRAM domain containing

Basic information

Region (hg38): 17:75845698-75856507

Links

ENSG00000132471 ∙ NCBI:23558 ∙ OMIM:606962 ∙ HGNC:12738 ∙ Uniprot:Q969T9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive 107 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• hearing loss, autosomal recessive 107 (Limited), mode of inheritance: Unknown
• hearing loss, autosomal recessive (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 107	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	26881968

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WBP2 gene.

• not provided (55 variants)
• Inborn genetic diseases (12 variants)
• Hearing loss, autosomal recessive 107 (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WBP2 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				10	3	13
missense		1	24	3		28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	3	6
non coding				10	9	19
Total	0	1	24	23	12

Variants in WBP2

This is a list of pathogenic ClinVar variants found in the WBP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-75846755-C-T			Likely benign (Aug 22, 2022)
17-75846769-G-T			Uncertain significance (Jul 15, 2021)
17-75846776-C-T			Likely benign (Feb 16, 2023)
17-75846780-G-A			Uncertain significance (Jan 02, 2024)
17-75846800-G-A			Benign (Jan 11, 2024)
17-75846804-G-A			Likely benign (Oct 09, 2022)
17-75846811-C-T			Benign (May 16, 2021)
17-75846909-G-A			Uncertain significance (May 20, 2022)
17-75846917-G-A			Likely benign (Sep 29, 2023)
17-75846923-G-A			Likely benign (Aug 16, 2023)
17-75846958-C-T			Uncertain significance (Oct 22, 2021)
17-75846959-G-A			Benign (Jan 18, 2024)
17-75846969-G-A		Hearing loss, autosomal recessive 107	Pathogenic (Aug 24, 2017)
17-75846993-G-A		WBP2-related disorder	Likely benign (Feb 26, 2019)
17-75847002-C-A			Likely benign (Aug 09, 2022)
17-75847101-A-G			Benign (May 22, 2021)
17-75847467-C-T			Likely benign (May 15, 2023)
17-75847476-A-G			Likely benign (Jul 06, 2022)
17-75847508-C-T			Uncertain significance (Sep 24, 2021)
17-75847515-G-A			Likely benign (Oct 23, 2021)
17-75847522-G-A		not specified	Uncertain significance (Sep 22, 2023)
17-75847528-T-C			Uncertain significance (Aug 14, 2023)
17-75847535-G-A		not specified	Uncertain significance (May 30, 2023)
17-75847540-G-A			Uncertain significance (Oct 03, 2023)
17-75847545-G-A			Benign (Sep 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WBP2	protein_coding	protein_coding	ENST00000591399	8	10809

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.349	0.648	125743	0	4	125747	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.296	151	162	0.934	0.00000909	1687
Missense in Polyphen		42	46.847	0.89653		544
Synonymous	-0.214	67	64.8	1.03	0.00000438	495
Loss of Function	2.59	3	13.1	0.229	5.53e-7	166

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000340	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation (PubMed:16772533). In presence of estrogen, binds to ESR1- responsive promoters (PubMed:16772533). Required for YAP1 coactivation function on PGR activity (PubMed:16772533). Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533). Modulates expression of post-synaptic scaffolding proteins via regulation of ESR1, ESR2 and PGR (By similarity). {ECO:0000250|UniProtKB:P97765, ECO:0000269|PubMed:16772533}.
• Disease: DISEASE: Deafness, autosomal recessive, 107 (DFNB107) [MIM:617639]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:26881968}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: EGFR1 (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.350
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.66

Haploinsufficiency Scores

• pHI: 0.460
• hipred: Y
• hipred_score: 0.744
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wbp2
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: response to progesterone;positive regulation of intracellular estrogen receptor signaling pathway;response to estrogen;establishment of protein localization;positive regulation of gene expression, epigenetic;positive regulation of transcription by RNA polymerase II;progesterone receptor signaling pathway;cellular response to estrogen stimulus;positive regulation of histone H3-K14 acetylation
• Cellular component: nuclear chromatin;nucleus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;transcription coactivator activity;protein binding;estrogen receptor binding;chromatin DNA binding