VANGL1

VANGL planar cell polarity protein 1

Basic information

Region (hg38): 1:115641970-115698224

Links

ENSG00000173218

∙ NCBI:81839 ∙ OMIM:610132 ∙ HGNC:15512 ∙ Uniprot:Q8TAA9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Caudal regression syndrome; 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	Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	17409324

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VANGL1 gene.

Inborn_genetic_diseases (63 variants)
Neural_tube_defect (41 variants)
Sacral_defect_with_anterior_meningocele (40 variants)
not_provided (28 variants)
not_specified (7 variants)
Neural_tube_defects,_susceptibility_to (6 variants)
VANGL1-related_disorder (4 variants)
Caudal_regression_sequence (2 variants)
Keratoconus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VANGL1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000138959.3. 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			6 clinvar	19 clinvar		25
missense		2 clinvar	75 clinvar	13 clinvar	3 clinvar	93
nonsense						0
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	1	2	83	32	3

Highest pathogenic variant AF is 0.0000322187

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VANGL1	protein_coding	protein_coding	ENST00000355485	7	56272

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0203	0.979	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0249	310	311	0.996	0.0000200	3408
Missense in Polyphen		111	113.97	0.97391		1294
Synonymous	-0.807	134	123	1.09	0.00000736	1078
Loss of Function	2.97	7	22.1	0.317	0.00000120	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Disease: DISEASE: Sacral defect with anterior meningocele (SDAM) [MIM:600145]: Form of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, or meningitis. Inheritance is autosomal dominant. {ECO:0000269|PubMed:17409324}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway (Consensus)

Recessive Scores

pRec: 0.127

Intolerance Scores

loftool: 0.0493
rvis_EVS: -0.24
rvis_percentile_EVS: 36.23

Haploinsufficiency Scores

pHI: 0.146
hipred: Y
hipred_score: 0.819
ghis: 0.494

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.608

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vangl1
Phenotype: growth/size/body region phenotype; cellular phenotype; skeleton phenotype; embryo phenotype; respiratory system 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; 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;

Gene ontology

Biological process: multicellular organism development;pigmentation;Wnt signaling pathway, planar cell polarity pathway
Cellular component: integral component of membrane;lateral plasma membrane
Molecular function: protein binding