VANGL1

protein-coding

VANGL planar cell polarity protein 1

Gene summary

This gene encodes a member of the tretraspanin family. The encoded protein may be involved in mediating intestinal trefoil factor induced wound healing in the intestinal mucosa. Mutations in this gene are associated with neural tube defects. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

MANE transcript

NM_138959.3

Inheritance

ClinVar variants

P:3U:100B:35

Top phenotype

Caudal regression syndrome; Neural tube defects

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr1:115,641,970-115,698,224

External References & Databases

Ensembl (ENSG00000173218)

Transcript & Mutation Effects

hg38 • Region Span ~56.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neural tube defects, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0020705

Submitter: PanelApp Australia

familial caudal dysgenesisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0010831

Submitter: PanelApp Australia

neural tube defects, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0020705

Submitter: G2P

Clinical Genomic Database (CGD)

Caudal regression syndrome; Neural tube defectsAD

Manifestation: Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 17409324

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VANGL1 variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 71

Sacral defect with anterior meningoceleTotal: 40

Neural tube defectTotal: 40

not providedTotal: 29

not specifiedTotal: 9

Neural tube defects, susceptibility toTotal: 6

VANGL1-related disorderTotal: 4

Caudal regression sequenceTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138959.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	19 clinvar		28
missense		2 clinvar	87 clinvar	13 clinvar	3 clinvar	105
nonsense						0
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	2	100	32	3	138

Highest pathogenic variant AF is 0.00003221869

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138959.3	RefSeq	NP_620409.1	7	MANE Select
ENST00000355485.7	Ensembl	ENSP00000347672.2	7	MANE Select
NM_001172411.2	RefSeq	NP_001165882.1	7	Standard
NM_001172412.2	RefSeq	NP_001165883.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Wnt signaling pathway - Homo sapiens (human)
Wnt Signaling Pathway

Biological Process

multicellular organism development
pigmentation
Wnt signaling pathway, planar cell polarity pathway

Molecular Function

protein binding

Cellular Component

integral component of membrane
lateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355485
Coding exons: 7
Length: 56272
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0249	310	311	0.996	0.0000200	3408
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.0493
RVIS EVS: -0.24
RVIS percentile EVS: 36.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.608

Gene Damage Prediction

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