WWTR1

WW domain containing transcription regulator 1

Basic information

Region (hg38): 3:149517234-149736714

Links

ENSG00000018408 ∙ NCBI:25937 ∙ OMIM:607392 ∙ HGNC:24042 ∙ Uniprot:Q9GZV5 ∙ 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 WWTR1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WWTR1 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				5		5
missense			21			21
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	5	0

Variants in WWTR1

This is a list of pathogenic ClinVar variants found in the WWTR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-149520916-A-G			Likely benign (Jun 01, 2022)
3-149520934-A-G			Likely benign (Aug 01, 2023)
3-149520981-C-T		not specified	Uncertain significance (Jun 17, 2024)
3-149520982-G-A			Likely benign (Feb 01, 2024)
3-149526043-A-G		not specified	Uncertain significance (Dec 28, 2023)
3-149526046-C-T		not specified	Uncertain significance (Dec 08, 2023)
3-149527860-T-C		not specified	Uncertain significance (Aug 12, 2021)
3-149527895-G-C			Likely benign (Jan 01, 2023)
3-149527912-C-G		not specified	Uncertain significance (Mar 20, 2023)
3-149527931-C-G		not specified	Uncertain significance (Nov 10, 2022)
3-149527962-G-A		not specified	Uncertain significance (Aug 02, 2021)
3-149542400-G-C		not specified	Uncertain significance (Jul 21, 2021)
3-149542434-C-T			Likely benign (Mar 01, 2023)
3-149542448-T-C		not specified	Uncertain significance (Jun 07, 2023)
3-149572888-T-C		not specified	Uncertain significance (Nov 15, 2021)
3-149572932-T-C		not specified	Uncertain significance (Sep 20, 2023)
3-149572947-G-A			Uncertain significance (Oct 01, 2022)
3-149572956-A-G		not specified	Uncertain significance (Jan 23, 2023)
3-149572959-G-A		not specified	Uncertain significance (Jan 24, 2024)
3-149572994-T-C		not specified	Uncertain significance (Oct 26, 2022)
3-149656960-T-C			Uncertain significance (Mar 01, 2022)
3-149656991-G-A		not specified	Uncertain significance (Jan 29, 2024)
3-149657017-C-T		not specified	Uncertain significance (Mar 29, 2022)
3-149657083-C-A		not specified	Uncertain significance (May 28, 2024)
3-149657111-T-C		not specified	Uncertain significance (Apr 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WWTR1	protein_coding	protein_coding	ENST00000465804	6	219480

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.939	0.0609	125742	0	3	125745	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	180	227	0.792	0.0000115	2618
Missense in Polyphen		42	74.206	0.56599		862
Synonymous	-0.00992	94	93.9	1.00	0.00000499	787
Loss of Function	3.46	2	17.7	0.113	8.75e-7	170

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADS and has a key role in coupling them to the transcriptional machinery such as the mediator complex. Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition. {ECO:0000269|PubMed:11118213, ECO:0000269|PubMed:18227151, ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321}.
• Pathway: Hippo signaling pathway - Homo sapiens (human);Hippo signaling pathway - multiple species - Homo sapiens (human);Adipogenesis;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;YAP1- and WWTR1 (TAZ)-stimulated gene expression;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;Signaling by Hippo;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.303
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63

Haploinsufficiency Scores

• pHI: 0.644
• hipred: Y
• hipred_score: 0.825
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wwtr1
• Phenotype: liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive 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); digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: wwtr1
• Affected structure: compact layer of ventricle
• Phenotype tag: abnormal
• Phenotype quality: oblique orientation

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;osteoblast differentiation;tissue homeostasis;negative regulation of protein phosphorylation;heart process;regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;negative regulation of protein kinase activity;positive regulation of cell population proliferation;positive regulation of epithelial to mesenchymal transition;protein ubiquitination;stem cell division;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;glomerulus development;multicellular organism growth;hippo signaling;negative regulation of fat cell differentiation;positive regulation of transcription by RNA polymerase II;mesenchymal cell differentiation;cilium assembly;regulation of SMAD protein signal transduction;kidney morphogenesis;regulation of metanephric nephron tubule epithelial cell differentiation;negative regulation of canonical Wnt signaling pathway
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;nuclear body
• Molecular function: transcription coactivator activity;transcription corepressor activity;protein binding;protein homodimerization activity