WNT5A

Wnt family member 5A, the group of Wnt family

Basic information

Region (hg38): 3:55465714-55490539

Links

ENSG00000114251 ∙ NCBI:7474 ∙ OMIM:164975 ∙ HGNC:12784 ∙ Uniprot:P41221 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant Robinow syndrome 1 (Moderate), mode of inheritance: AD
• autosomal dominant Robinow syndrome 1 (Definitive), mode of inheritance: AD
• autosomal dominant Robinow syndrome 1 (Moderate), mode of inheritance: AD
• autosomal dominant Robinow syndrome 1 (Strong), mode of inheritance: AD
• autosomal dominant Robinow syndrome (Supportive), mode of inheritance: AD
• autosomal dominant Robinow syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Robinow syndrome, autosomal dominant 1	AD	Renal	Individuals have been described with high-grade vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function	Craniofacial; Dental; Genitourinary; Musculoskeletal; Renal	5771504; 3746837; 17256787; 19918918; 24716670

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WNT5A gene.

• not provided (143 variants)
• Autosomal dominant Robinow syndrome 1 (49 variants)
• Inborn genetic diseases (15 variants)
• not specified (6 variants)
• WNT5A-related condition (2 variants)
• Short stature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WNT5A 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	31	4	36
missense	1	3	72	3	3	82
nonsense						0
start loss						0
frameshift			4			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	4		6
non coding			11	14	10	35
Total	1	3	89	48	17

Variants in WNT5A

This is a list of pathogenic ClinVar variants found in the WNT5A region.

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

Position	Type	Phenotype	Significance	ClinVar
3-55465912-T-TA		Autosomal dominant Robinow syndrome 1	Benign (Jun 14, 2016)
3-55466152-CAG-C		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55467360-A-AT		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55467361-TTTC-T		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55467363-TC-T		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55467378-TTTG-T		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55467380-TG-T		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55468081-C-T			Likely benign (May 19, 2021)
3-55468138-TA-T			Benign (May 19, 2021)
3-55468138-TAA-T		Autosomal dominant Robinow syndrome 1	Conflicting classifications of pathogenicity (May 17, 2021)
3-55468138-T-TA		Autosomal dominant Robinow syndrome 1	Conflicting classifications of pathogenicity (May 16, 2021)
3-55468138-T-TAA		Autosomal dominant Robinow syndrome 1	Conflicting classifications of pathogenicity (May 16, 2021)
3-55468138-T-TAAA			Likely benign (May 19, 2021)
3-55468138-T-TAAAA			Benign (May 18, 2021)
3-55468223-G-A			Benign (May 21, 2021)
3-55468622-A-ATATATT		Autosomal dominant Robinow syndrome 1	Likely benign (Jun 14, 2016)
3-55468640-T-TTA		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55468650-GTA-G		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55468650-G-GTA		Autosomal dominant Robinow syndrome 1	Uncertain significance (Jun 14, 2016)
3-55470054-G-A			Likely benign (Oct 28, 2019)
3-55470107-C-T		WNT5A-related disorder	Likely benign (Dec 27, 2023)
3-55470112-C-T		Autosomal dominant Robinow syndrome 1	Uncertain significance (Dec 12, 2023)
3-55470119-C-T			Likely benign (Jun 09, 2023)
3-55470122-C-T		WNT5A-related disorder	Likely benign (Jan 16, 2024)
3-55470155-G-A			Likely benign (Mar 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WNT5A	protein_coding	protein_coding	ENST00000474267	5	24231

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.987	0.0127	124736	0	1	124737	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	159	246	0.645	0.0000167	2480
Missense in Polyphen		42	105.92	0.39653		962
Synonymous	0.587	96	104	0.927	0.00000786	716
Loss of Function	3.67	1	17.6	0.0568	9.05e-7	189

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)	0.00000885	0.00000885
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. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor (PubMed:15735754). Mediates motility of melanoma cells (PubMed:17426020). Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes (By similarity). {ECO:0000250|UniProtKB:P22725, ECO:0000250|UniProtKB:Q27Q52, ECO:0000269|PubMed:15735754, ECO:0000269|PubMed:17426020}.
• Disease: DISEASE: Robinow syndrome, autosomal dominant 1 (DRS1) [MIM:180700]: A disease characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. The clinical signs are generally milder in dominant cases. {ECO:0000269|PubMed:19918918}. 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);Axon guidance - 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);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);WNT-Core;MicroRNAs in cardiomyocyte hypertrophy;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Differentiation Pathway;Extracellular vesicle-mediated signaling in recipient cells;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;Vesicle-mediated transport;Membrane Trafficking;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;Clathrin-mediated endocytosis;Asymmetric localization of PCP proteins;WNT5A-dependent internalization of FZD4;WNT5A-dependent internalization of FZD2, FZD5 and ROR2;PCP/CE pathway;Negative regulation of TCF-dependent signaling by WNT ligand antagonists;Ca2+ pathway;Beta-catenin independent WNT signaling;Noncanonical Wnt signaling pathway;Cargo recognition for clathrin-mediated endocytosis;WNT ligand biogenesis and trafficking;GPCR signaling-G alpha i;Wnt;Wnt Canonical;Wnt signaling network;Validated targets of C-MYC transcriptional repression;TCF dependent signaling in response to WNT;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.637

Intolerance Scores

• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.751
• hipred: Y
• hipred_score: 0.853
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wnt5a
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary 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; limbs/digits/tail phenotype; hematopoietic system phenotype; 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); 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); normal phenotype; reproductive system phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: wnt5a
• Affected structure: perichondrium
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: activation of MAPK activity;establishment of planar polarity;somitogenesis;epithelial to mesenchymal transition;positive regulation of endothelial cell proliferation;heart looping;positive regulation of mesenchymal cell proliferation;lens development in camera-type eye;positive regulation of cytokine secretion involved in immune response;type B pancreatic cell development;planar cell polarity pathway involved in axis elongation;optic cup formation involved in camera-type eye development;Wnt signaling pathway, calcium modulating pathway;activation of JUN kinase activity;axon guidance;hindgut morphogenesis;midgut development;male gonad development;anterior/posterior axis specification, embryo;response to organic substance;regulation of signaling receptor activity;positive regulation of endothelial cell migration;positive regulation of gene expression;positive regulation of peptidyl-threonine phosphorylation;positive regulation of T cell chemotaxis;positive regulation of neuron projection development;Wnt signaling pathway;olfactory bulb interneuron development;neuron differentiation;keratinocyte differentiation;lung development;negative regulation of BMP signaling pathway;positive regulation of protein binding;activation of protein kinase B activity;positive regulation of interferon-gamma production;positive regulation of interleukin-6 production;positive regulation of peptidyl-serine phosphorylation;cellular protein localization;non-canonical Wnt signaling pathway;post-anal tail morphogenesis;chemoattraction of serotonergic neuron axon;chemorepulsion of dopaminergic neuron axon;non-canonical Wnt signaling pathway via JNK cascade;negative regulation of fibroblast growth factor receptor signaling pathway;wound healing;embryonic digit morphogenesis;positive regulation of macrophage activation;negative regulation of apoptotic process;regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of chemokine biosynthetic process;cell fate commitment;establishment of epithelial cell apical/basal polarity;negative regulation of fat cell differentiation;positive regulation of protein catabolic process;positive regulation of G protein-coupled receptor signaling pathway;positive regulation of angiogenesis;positive regulation of ossification;positive regulation of endocytosis;positive regulation of meiotic nuclear division;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of melanin biosynthetic process;positive regulation of fibroblast proliferation;paraxial mesoderm formation;notochord morphogenesis;embryonic skeletal system development;genitalia development;negative regulation of axon extension involved in axon guidance;hypophysis morphogenesis;negative regulation of epithelial cell proliferation;positive regulation of interleukin-1 beta secretion;regulation of inflammatory response;positive regulation of inflammatory response;regulation of synapse organization;positive regulation of NF-kappaB transcription factor activity;cartilage development;positive regulation of timing of anagen;negative regulation of synapse assembly;convergent extension involved in axis elongation;convergent extension involved in organogenesis;uterus development;cervix development;vagina development;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;urinary bladder development;face development;positive regulation of type I interferon-mediated signaling pathway;lateral sprouting involved in mammary gland duct morphogenesis;mesenchymal-epithelial cell signaling;negative regulation of prostatic bud formation;mammary gland branching involved in thelarche;epithelial cell proliferation involved in mammary gland duct elongation;positive regulation of response to cytokine stimulus;regulation of branching involved in mammary gland duct morphogenesis;planar cell polarity pathway involved in gastrula mediolateral intercalation;mesodermal to mesenchymal transition involved in gastrulation;positive regulation of macrophage cytokine production;membrane organization;positive regulation of cartilage development;planar cell polarity pathway involved in outflow tract morphogenesis;planar cell polarity pathway involved in ventricular septum morphogenesis;planar cell polarity pathway involved in cardiac right atrium morphogenesis;planar cell polarity pathway involved in cardiac muscle tissue morphogenesis;planar cell polarity pathway involved in pericardium morphogenesis;secondary palate development;positive regulation of thymocyte apoptotic process;cellular response to lipopolysaccharide;cellular response to calcium ion;cellular response to retinoic acid;cellular response to interferon-gamma;hematopoietic stem cell proliferation;cellular response to transforming growth factor beta stimulus;negative regulation of mesenchymal cell proliferation;primitive streak formation;positive regulation of protein kinase C signaling;negative regulation of canonical Wnt signaling pathway;cochlea morphogenesis;planar cell polarity pathway involved in neural tube closure;activation of GTPase activity;melanocyte proliferation;presynapse assembly;postsynapse assembly;regulation of postsynapse organization;regulation of postsynaptic cytosolic calcium ion concentration;positive regulation of neuron projection arborization;positive regulation of protein kinase C activity;positive regulation of neuron death;positive regulation of protein localization to synapse;regulation of cellular protein localization;positive regulation of tumor necrosis factor secretion;excitatory synapse assembly;inhibitory synapse assembly;negative regulation of cell proliferation in midbrain;planar cell polarity pathway involved in axon guidance;Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation;planar cell polarity pathway involved in midbrain dopaminergic neuron differentiation;positive regulation of cell-cell adhesion mediated by cadherin;positive regulation of non-canonical Wnt signaling pathway;positive regulation of interleukin-8 secretion
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi lumen;plasma membrane;cell surface;clathrin-coated vesicle membrane;endocytic vesicle membrane;clathrin-coated endocytic vesicle membrane;collagen-containing extracellular matrix;extracellular exosome;postsynapse;glutamatergic synapse
• Molecular function: DNA-binding transcription factor activity;frizzled binding;receptor tyrosine kinase-like orphan receptor binding;cytokine activity;protein binding;phospholipid binding;protein domain specific binding;transcription regulatory region DNA binding;receptor ligand activity;chemoattractant activity involved in axon guidance