YAP1

Yes1 associated transcriptional regulator

Basic information

Region (hg38): 11:102110446-102233424

Links

ENSG00000137693 ∙ NCBI:10413 ∙ OMIM:606608 ∙ HGNC:16262 ∙ Uniprot:P46937 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• uveal coloboma-cleft lip and palate-intellectual disability (Strong), mode of inheritance: AD
• uveal coloboma-cleft lip and palate-intellectual disability (Strong), mode of inheritance: AD
• uveal coloboma-cleft lip and palate-intellectual disability (Strong), mode of inheritance: AD
• uveal coloboma-cleft lip and palate-intellectual disability (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ocular coloboma with or without hearing impairment, cleft lip/palate, and/or impaired intellectual development	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic; Renal	24462371

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YAP1 gene.

• not provided (38 variants)
• Uveal coloboma-cleft lip and palate-intellectual disability (7 variants)
• Inborn genetic diseases (6 variants)
• not specified (1 variants)
• YAP1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YAP1 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				8	3	11
missense	1		18	4	1	24
nonsense			2			2
start loss			1			1
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				2	9	11
Total	1	1	21	14	13

Variants in YAP1

This is a list of pathogenic ClinVar variants found in the YAP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-102110546-T-C			Benign (Jun 19, 2021)
11-102110849-A-C			Uncertain significance (Nov 03, 2021)
11-102110859-G-A			Uncertain significance (Apr 01, 2022)
11-102110868-C-T			Uncertain significance (Jun 15, 2022)
11-102110869-G-A			Benign (Dec 25, 2023)
11-102110881-G-T			Likely benign (Jan 04, 2022)
11-102110898-G-T		not specified	Uncertain significance (Nov 14, 2023)
11-102110910-C-T		not specified	Uncertain significance (Oct 02, 2023)
11-102110917-C-T			Likely benign (Sep 05, 2023)
11-102110934-C-A		not specified	Uncertain significance (Oct 13, 2023)
11-102110955-C-CGGCACCCGCGGCGACCCAGGCGGCGCCGCA			Uncertain significance (Sep 16, 2018)
11-102110971-CCAGGCGGCGCCG-C		YAP1-related disorder	Uncertain significance (Dec 29, 2023)
11-102110992-C-T			Likely benign (Dec 15, 2022)
11-102111008-A-C			Uncertain significance (May 23, 2023)
11-102111011-G-T		Uveal coloboma-cleft lip and palate-intellectual disability	Uncertain significance (Oct 29, 2018)
11-102111052-C-G		YAP1-related disorder	Likely benign (May 28, 2019)
11-102111084-A-G			Uncertain significance (Nov 03, 2021)
11-102111091-C-T			Likely benign (Jun 19, 2023)
11-102111105-T-C		Uveal coloboma-cleft lip and palate-intellectual disability	Pathogenic (May 04, 2022)
11-102111129-CCTT-C			Uncertain significance (Jan 05, 2023)
11-102111153-A-T		not specified	Uncertain significance (Nov 17, 2022)
11-102111161-T-C		YAP1-related disorder • not specified	Uncertain significance (Sep 22, 2023)
11-102111164-C-A			Likely benign (Apr 30, 2018)
11-102111177-C-T		YAP1-related disorder	Likely benign (Jun 03, 2019)
11-102113897-C-T			Benign (Nov 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YAP1	protein_coding	protein_coding	ENST00000282441	9	122963

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000823	124519	0	5	124524	0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	189	271	0.697	0.0000134	3283
Missense in Polyphen		20	56.818	0.352		729
Synonymous	-0.406	107	102	1.05	0.00000489	1020
Loss of Function	4.44	1	24.9	0.0401	0.00000138	242

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	0.00	0.00
European (Non-Finnish)	0.0000465	0.0000443
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical 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 (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637). 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 (PubMed:18158288). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). Plays a key role to control cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288). The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction (PubMed:18579750). {ECO:0000269|PubMed:17974916, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:25778702}.
• Disease: DISEASE: Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation (COB1) [MIM:120433]: An autosomal dominant disease characterized by uveal colobomata, microphthalmia, cataract and cleft lip/palate. Considerable variability is observed among patients, uveal colobomata being the most constant feature. Some patients manifest mental retardation of varying degree and/or sensorineural, mid-frequency hearing loss. {ECO:0000269|PubMed:24462371}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hippo signaling pathway - Homo sapiens (human);Hippo signaling pathway - multiple species - Homo sapiens (human);Mesodermal Commitment Pathway;Rac1-Pak1-p38-MMP-2 pathway;TGF-beta Signaling Pathway;miR-509-3p alteration of YAP1-ECM axis;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Signal Transduction;Gene expression (Transcription);RUNX3 regulates YAP1-mediated transcription;Transcriptional regulation by RUNX3;Generic Transcription Pathway;RNA Polymerase II Transcription;YAP1- and WWTR1 (TAZ)-stimulated gene expression;p73 transcription factor network;ErbB4 signaling events;Signaling by Hippo;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Nuclear signaling by ERBB4;Signaling by ERBB4;Signaling by Receptor Tyrosine Kinases;Transcriptional regulation by RUNX1;Validated transcriptional targets of deltaNp63 isoforms;TGF-beta receptor signaling (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.0213
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.627
• hipred: Y
• hipred_score: 0.831
• ghis: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.620

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Yap1
• 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); 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); neoplasm; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; renal/urinary 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); digestive/alimentary phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: yap1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased functionality

Gene ontology

• Biological process: cell morphogenesis;vasculogenesis;tissue homeostasis;heart process;embryonic heart tube morphogenesis;transcription initiation from RNA polymerase II promoter;cellular response to DNA damage stimulus;cell population proliferation;regulation of keratinocyte proliferation;keratinocyte differentiation;negative regulation of epithelial cell differentiation;notochord development;response to progesterone;positive regulation of intracellular estrogen receptor signaling pathway;somatic stem cell population maintenance;hippo signaling;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;paraxial mesoderm development;lateral mesoderm development;regulation of neurogenesis;progesterone receptor signaling pathway;positive regulation of cardiac muscle cell proliferation;contact inhibition;bud elongation involved in lung branching;lung epithelial cell differentiation;cardiac muscle tissue regeneration;protein-containing complex assembly;cellular response to retinoic acid;cellular response to gamma radiation;regulation of stem cell proliferation;regulation of metanephric nephron tubule epithelial cell differentiation;positive regulation of canonical Wnt signaling pathway;regulation of hematopoietic stem cell differentiation;positive regulation of stem cell population maintenance;negative regulation of nucleic acid-templated transcription;negative regulation of stem cell differentiation;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;membrane;TEAD-1-YAP complex;TEAD-2-YAP complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;chromatin binding;transcription coactivator activity;transcription corepressor activity;protein binding;protein C-terminus binding;activating transcription factor binding;transcription regulatory region DNA binding;protein heterodimerization activity;proline-rich region binding