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.

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.

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			6	13		19
missense			36	5	4	45
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			84	32	35	151
Total	0	0	127	50	39

Variants in VANGL1

This is a list of pathogenic ClinVar variants found in the VANGL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-115641975-A-AGCG		Neural tube defect • Caudal regression sequence	Uncertain significance (Jun 14, 2016)
1-115641985-G-A		Neural tube defect • Sacral defect with anterior meningocele	Benign/Likely benign (Apr 27, 2017)
1-115641998-G-C		Sacral defect with anterior meningocele • Neural tube defect	Benign (Jan 13, 2018)
1-115642000-C-A		Neural tube defect • Sacral defect with anterior meningocele	Benign (Jan 12, 2018)
1-115642053-C-A		Neural tube defect • Sacral defect with anterior meningocele	Uncertain significance (Jan 13, 2018)
1-115642079-G-T		Sacral defect with anterior meningocele • Neural tube defect	Uncertain significance (Jan 13, 2018)
1-115651261-T-TC		not specified	Benign (Dec 30, 2019)
1-115651299-G-C		Neural tube defect • Sacral defect with anterior meningocele	Conflicting classifications of pathogenicity (Jan 13, 2018)
1-115651390-C-T		Neural tube defect • Caudal regression sequence	Uncertain significance (Jun 14, 2016)
1-115651423-G-A		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
1-115651454-C-T		Keratoconus	Uncertain significance (Feb 18, 2018)
1-115651464-G-A		Sacral defect with anterior meningocele • Neural tube defect	Conflicting classifications of pathogenicity (Jan 12, 2018)
1-115651481-A-C		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
1-115659527-G-A			Benign (Jun 19, 2021)
1-115659642-G-A		Sacral defect with anterior meningocele • Neural tube defect • VANGL1-related disorder	Conflicting classifications of pathogenicity (Apr 27, 2017)
1-115659667-C-T		Neural tube defect • Sacral defect with anterior meningocele	Conflicting classifications of pathogenicity (Jan 12, 2018)
1-115659672-C-T		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
1-115659683-C-T		Neural tube defect • Sacral defect with anterior meningocele	Conflicting classifications of pathogenicity (Jan 13, 2018)
1-115659707-C-T		VANGL1-related disorder	Likely benign (Aug 06, 2019)
1-115659723-ACT-A			Uncertain significance (Sep 16, 2018)
1-115659765-G-A		Inborn genetic diseases	Uncertain significance (May 04, 2023)
1-115663657-C-T			Benign (Dec 31, 2018)
1-115663672-G-C		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
1-115663687-G-A		Sacral defect with anterior meningocele • Neural tube defect	Conflicting classifications of pathogenicity (Oct 17, 2018)
1-115663704-C-T		Neural tube defect	Benign (May 28, 2019)

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