WNT3

Wnt family member 3, the group of Wnt family

Basic information

Region (hg38): 17:46762505-46833154

Previous symbols: [ "INT4" ]

Links

ENSG00000108379 ∙ NCBI:7473 ∙ OMIM:165330 ∙ HGNC:12782 ∙ Uniprot:P56703 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• tetraamelia syndrome 1 (Moderate), mode of inheritance: AR
• tetraamelia syndrome 1 (Definitive), mode of inheritance: AR
• tetraamelia-multiple malformations syndrome (Supportive), mode of inheritance: AR
• tetraamelia syndrome 1 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tetraamelia syndrome 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Renal	14872406

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WNT3 gene.

• not provided (82 variants)
• Inborn genetic diseases (7 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WNT3 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	25	1	27
missense			25			25
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	3		4
non coding				22	7	29
Total	0	0	27	47	8

Variants in WNT3

This is a list of pathogenic ClinVar variants found in the WNT3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-46768080-A-G			Benign (Jul 07, 2018)
17-46768172-C-T			Likely benign (Jan 16, 2019)
17-46768337-C-T		not specified	Uncertain significance (Jan 17, 2023)
17-46768391-T-C			Uncertain significance (Jan 30, 2023)
17-46768419-C-T			Likely benign (Aug 06, 2022)
17-46768467-G-A		WNT3-related disorder	Likely benign (Apr 14, 2023)
17-46768473-G-A			Likely benign (Jun 10, 2023)
17-46768485-A-G			Likely benign (Oct 22, 2023)
17-46768511-A-C			Uncertain significance (Dec 31, 2023)
17-46768516-C-T			Uncertain significance (Apr 13, 2021)
17-46768545-G-A			Likely benign (Jul 17, 2023)
17-46768557-G-A			Likely benign (Jul 25, 2022)
17-46768560-G-A			Likely benign (Mar 29, 2023)
17-46768572-C-T			Likely benign (Aug 15, 2022)
17-46768578-C-T			Likely benign (May 19, 2023)
17-46768596-C-T			Likely benign (Aug 11, 2021)
17-46768614-G-A			Likely benign (Aug 16, 2022)
17-46768671-G-A			Likely benign (Jan 02, 2024)
17-46768677-C-T			Likely benign (Mar 11, 2022)
17-46768678-T-C			Uncertain significance (Oct 17, 2022)
17-46768698-G-A			Likely benign (Aug 02, 2023)
17-46768700-T-C			Uncertain significance (Nov 28, 2022)
17-46768746-G-A			Likely benign (Apr 18, 2022)
17-46768750-C-T		Bladder exstrophy-epispadias-cloacal extrophy complex	Uncertain significance (Mar 31, 2015)
17-46768806-G-C			Likely benign (Apr 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WNT3	protein_coding	protein_coding	ENST00000225512	4	70649

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.875	0.125	122322	0	1	122323	0.00000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.18	109	251	0.435	0.0000184	2313
Missense in Polyphen		30	99.567	0.3013		918
Synonymous	0.595	106	114	0.929	0.00000937	706
Loss of Function	3.19	2	15.6	0.128	7.59e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000203	0.000101
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:26902720). Required for normal gastrulation, formation of the primitive streak, and for the formation of the mesoderm during early embryogenesis. Required for normal formation of the apical ectodermal ridge (By similarity). Required for normal embryonic development, and especially for limb development (PubMed:14872406). {ECO:0000250|UniProtKB:P17553, ECO:0000269|PubMed:14872406, ECO:0000269|PubMed:26902720, ECO:0000305}.
• Disease: DISEASE: Tetraamelia syndrome 1 (TETAMS1) [MIM:273395]: A form of tetraamelia, a rare disease characterized by rudimentary appendages or complete absence of all four limbs, and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. TETAMS1 patients manifest complete limb agenesis without defects of scapulae or clavicles. Other features include bilateral cleft lip/palate, diaphragmatic defect with bilobar right lung, renal and adrenal agenesis, pelvic hypoplasia, and urogenital defects. TETAMS1 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:14872406}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric cancer - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Breast cancer - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Endoderm Differentiation;Mesodermal Commitment Pathway;EDA Signalling in Hair Follicle Development;ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;Wnt Signaling in Kidney Disease;EMT transition in Colorectal Cancer;Wnt Signaling Pathway;DNA Damage Response (only ATM dependent);Signaling by GPCR;Signaling by WNT;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;WNT ligand biogenesis and trafficking;GPCR signaling-G alpha i;Wnt;Wnt Canonical;Wnt signaling network;TCF dependent signaling in response to WNT;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.270

Intolerance Scores

• loftool: 0.0728
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.547
• hipred: Y
• hipred_score: 0.809
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wnt3
• Phenotype: growth/size/body region phenotype; cellular phenotype; embryo phenotype; normal 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); reproductive system phenotype; limbs/digits/tail phenotype

Zebrafish Information Network

• Gene name: wnt3
• Affected structure: cloaca
• Phenotype tag: abnormal
• Phenotype quality: increased width

Gene ontology

• Biological process: cell morphogenesis;mesoderm formation;gamete generation;axon guidance;anterior/posterior axis specification;dorsal/ventral axis specification;regulation of signaling receptor activity;positive regulation of gene expression;Wnt signaling pathway;positive regulation of Wnt signaling pathway;neuron differentiation;embryonic forelimb morphogenesis;embryonic hindlimb morphogenesis;canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation;canonical Wnt signaling pathway involved in osteoblast differentiation;cell fate commitment;positive regulation of collateral sprouting in absence of injury;negative regulation of axon extension involved in axon guidance;regulation of neurogenesis;Spemann organizer formation at the anterior end of the primitive streak;canonical Wnt signaling pathway;limb bud formation;head morphogenesis;mammary gland epithelium development;cellular response to retinoic acid;stem cell proliferation;canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation;canonical Wnt signaling pathway involved in stem cell proliferation
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi lumen;plasma membrane;endocytic vesicle membrane;extracellular matrix;extracellular exosome;Wnt signalosome
• Molecular function: frizzled binding;protein binding;protein domain specific binding;receptor ligand activity