VANGL2

VANGL planar cell polarity protein 2

Basic information

Region (hg38): 1:160400564-160428678

Links

ENSG00000162738

∙ NCBI:57216 ∙ OMIM:600533 ∙ HGNC:15511 ∙ Uniprot:Q9ULK5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neural tube defects, susceptibility to (Limited), mode of inheritance: Unknown
neural tube defects, susceptibility to (Moderate), mode of inheritance: AD
neural tube defects, susceptibility to (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neural tube defects	AD	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	Musculoskeletal	20558380; 20738329

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VANGL2 gene.

Inborn_genetic_diseases (42 variants)
not_provided (9 variants)
Neural_tube_defects,_susceptibility_to (6 variants)
VANGL2-related_disorder (5 variants)
Neural_tube_defect (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VANGL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020335.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	1 clinvar	5
missense			50 clinvar	1 clinvar	3 clinvar	54
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	5	4

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VANGL2	protein_coding	protein_coding	ENST00000368061	7	28093

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.843	0.157	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	253	326	0.777	0.0000234	3345
Missense in Polyphen		77	126.11	0.6106		1254
Synonymous	0.00209	143	143	1.00	0.0000100	1104
Loss of Function	3.75	4	23.7	0.169	0.00000155	229

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000925	0.0000924
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: Involved in the control of early morphogenesis and patterning of both axial midline structures and the development of neural plate. Plays a role in the regulation of planar cell polarity, particularly in the orientation of stereociliary bundles in the cochlea. Required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process. Required for cell surface localization of FZD3 and FZD6 in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q91ZD4}.;
Disease: DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. {ECO:0000269|PubMed:20558380}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;Asymmetric localization of PCP proteins;PCP/CE pathway;Beta-catenin independent WNT signaling (Consensus)

Recessive Scores

pRec: 0.349

Intolerance Scores

loftool: 0.0404
rvis_EVS: -1.02
rvis_percentile_EVS: 7.94

Haploinsufficiency Scores

pHI: 0.706
hipred: Y
hipred_score: 0.798
ghis: 0.617

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.275

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vangl2
Phenotype: growth/size/body region phenotype; cellular phenotype; limbs/digits/tail phenotype; craniofacial phenotype; vision/eye 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); 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); normal phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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);

Zebrafish Information Network

Gene name: vangl2
Affected structure: neuroepithelial cell
Phenotype tag: abnormal
Phenotype quality: mislocalised

Gene ontology

Biological process: establishment of planar polarity;neural tube closure;hair follicle development;heart looping;membranous septum morphogenesis;muscular septum morphogenesis;planar cell polarity pathway involved in axis elongation;Rho protein signal transduction;anterior/posterior pattern specification;heparan sulfate proteoglycan biosynthetic process;convergent extension involved in neural plate elongation;regulation of Wnt signaling pathway;glomerulus development;regulation of actin cytoskeleton organization;somatic stem cell population maintenance;cell migration involved in kidney development;post-anal tail morphogenesis;dopaminergic neuron axon guidance;serotonergic neuron axon guidance;wound healing;positive regulation of JUN kinase activity;apical protein localization;establishment or maintenance of epithelial cell apical/basal polarity;somatic stem cell division;establishment of body hair planar orientation;digestive tract morphogenesis;convergent extension involved in axis elongation;inner ear receptor cell stereocilium organization;orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis;planar dichotomous subdivision of terminal units involved in lung branching morphogenesis;lateral sprouting involved in lung morphogenesis;kidney morphogenesis;planar cell polarity pathway involved in heart morphogenesis;cochlea morphogenesis;establishment of planar polarity involved in neural tube closure;planar cell polarity pathway involved in neural tube closure;planar cell polarity pathway involved in axon guidance;non-motile cilium assembly
Cellular component: stress fiber;plasma membrane;cell-cell junction;integral component of membrane;basolateral plasma membrane;apical plasma membrane;lateral plasma membrane;COPII-coated ER to Golgi transport vesicle;cell pole
Molecular function: protein binding