VANGL1

Summary

VANGL1 (VANGL planar cell polarity protein 1, HGNC:15512) is a protein-coding gene on chromosome 1p13.1, encoding Vang-like protein 1 (Q8TAA9).

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.

Source: NCBI Gene 81839 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neural tube defects, susceptibility to (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 301 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 58
• MANE Select transcript: NM_138959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15512
Approved symbol	VANGL1
Name	VANGL planar cell polarity protein 1
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Aliases	STB2
Ensembl gene	ENSG00000173218
Ensembl biotype	protein_coding
OMIM	610132
Entrez	81839

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000310260, ENST00000355485, ENST00000369509, ENST00000369510, ENST00000474344, ENST00000478369, ENST00000879938, ENST00000879939, ENST00000879940, ENST00000879941, ENST00000927747, ENST00000927748

RefSeq mRNA: 3 — MANE Select: NM_138959 NM_001172411, NM_001172412, NM_138959

CCDS: CCDS53350, CCDS883

Canonical transcript exons

ENST00000355485 — 8 exons

Exon	Start	End
ENSE00001425364	115641970	115642086
ENSE00003537200	115682364	115682497
ENSE00003598068	115683944	115684076
ENSE00003845520	115691119	115698221
ENSE00003888943	115663661	115664268
ENSE00003889623	115685293	115685527
ENSE00003890614	115659641	115659773
ENSE00003891059	115651277	115651484

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 90.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3565 / max 307.6911, expressed in 1738 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4789	13.6869	1732
4788	0.8499	409
4790	0.5229	303
4792	0.2369	50
4791	0.0310	7
4794	0.0173	3
4793	0.0117	3

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	90.58	gold quality
corpus epididymis	UBERON:0004359	90.40	gold quality
caput epididymis	UBERON:0004358	90.08	gold quality
oral cavity	UBERON:0000167	88.33	gold quality
gingiva	UBERON:0001828	87.25	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.00	gold quality
epithelium of bronchus	UBERON:0002031	86.38	gold quality
gingival epithelium	UBERON:0001949	85.94	gold quality
bronchus	UBERON:0002185	85.56	gold quality
mammalian vulva	UBERON:0000997	84.78	gold quality
epithelium of nasopharynx	UBERON:0001951	84.56	silver quality
nasopharynx	UBERON:0001728	84.54	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.63	gold quality
cauda epididymis	UBERON:0004360	83.50	gold quality
visceral pleura	UBERON:0002401	82.84	gold quality
stromal cell of endometrium	CL:0002255	81.93	gold quality
palpebral conjunctiva	UBERON:0001812	81.59	gold quality
nipple	UBERON:0002030	81.23	gold quality
parietal pleura	UBERON:0002400	81.21	gold quality
esophagus squamous epithelium	UBERON:0006920	80.93	gold quality
lower lobe of lung	UBERON:0008949	80.90	gold quality
endometrium	UBERON:0001295	80.74	gold quality
pleura	UBERON:0000977	80.71	gold quality
mammary duct	UBERON:0001765	80.29	silver quality
mucosa of sigmoid colon	UBERON:0004993	80.17	gold quality
calcaneal tendon	UBERON:0003701	80.05	gold quality
eye	UBERON:0000970	79.97	gold quality
secondary oocyte	CL:0000655	79.95	gold quality
trabecular bone tissue	UBERON:0002483	79.90	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, STAT1

miRNA regulators (miRDB)

334 targeting VANGL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4745-5P	99.98	65.95	1028

Literature-anchored findings (GeneRIF, showing 36)

• Molecular cloning and characterization of Strabismus 2 (PMID:11956595)
• VANGL protein may serve as an effector mediating the intestinal trefoil factor (ITF) healing response of the intestinal mucosa. (PMID:16410243)
• In a protein-protein interaction assay V239I abolished interaction of VANGL1 protein with its binding partners, disheveled-1, -2, and -3. These findings implicate VANGL1 as a risk factor in human neural-tube defects. (PMID:17409324)
• VANGL1 increases invasion and migration of mouse squamous cancer cells and promotes pulmonary metastasis in a mouse squamous tumor model. (PMID:19166844)
• role of VANGL1 as a risk factor in the development of spinal neural tube defects (PMID:19319979)
• This study demonstrates a high degree of functional conservation of VANGL genes across evolution and provides a model system for studying potential variants identified in human neural tube defects. (PMID:20043994)
• KITENIN plays an important role in human gastric cancer progression by AP-1 activation. (PMID:20944126)
• Loss of membrane targeting of Vangl1 and Vangl2 proteins causes neural tube defects. (PMID:21142127)
• a compact membrane-associated portion with very short predicted extra- and intracellular loops, while the protein harbors a large intracellular domain (PMID:21291170)
• KITENIN is associated with human colorectal cancer progression including invasion and metastasis. (PMID:21418393)
• NOS1AP colocalizes with both SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells, but does not colocalize with either SCRIB or VANGL1 at cell junctions in normal breast cells (PMID:22179838)
• KITENIN is associated with tumor invasiveness and metastasis in human oral cavity squamous cell carcinoma. (PMID:22840317)
• The rs4839469 allele of VANGL1 was obviously associated with neural tube defects (NTDs). And genotype GC increased the risk of NTDs, changes in the three-dimensional protein structure may have impacted its biological functions. (PMID:24407469)
• The results show that the Vangl1 amino terminus lacks PM targeting determinants, and these are restricted to the carboxy terminus, including the predicted PDZBM motif at the C-terminus (PMID:24452931)
• Elevated KITENIN expression is associated with drug resistance in colorectal cancer. (PMID:24893630)
• Findings identify that KITENIN-targeting miR-124, miR-27a, and miR-30b function as endogenous inhibitors of colorectal cancer cell motility and demonstrate that miR-124 plays a suppressor role in colorectal tumorigenesis. (PMID:24909917)
• These results strongly suggest that R181 and R274 play critical roles in Vangl protein function and that their mutations cause neural tube defects in humans. (PMID:25068569)
• VANGL1 mutations are associated with neural tube defects. (PMID:25208524)
• High levels of KITENIN increased glioma invasiveness and progression, and are associated with the up-regulation of EMT and stemness markers. (PMID:25605251)
• Authors silenced VANGL1 gene expression in the HepG2 HCC cell line by stable transfection with a vector containing siRNA template for VANGL1 and investigated the change in cell invasion and motility. (PMID:25874746)
• Results found that KITENIN is associated with tumor progression by enhancing angiogenesis in colorectal cancer. (PMID:26496979)
• a novel and ultrasensitive sandwich-type immunosensor was fabricated to detect Vangl in human serum using C60-templated AuPt as labels and rGO-TEPA-PTC-NH2 as the platform. (PMID:26735870)
• We first propose the use of a DNA biosensor to detect the missense single nucleotide polymorphism (rs4839469 c.346G>A p.Ala116Thr) of the vangl1 gene (PMID:26914375)
• Study provides evidence that KITENIN functions in the maintenance of a higher expression level of ErbB4 in advanced colorectal cancer tissues, independent of ubiquitin-mediated degradation via Nrdp1. (PMID:27648936)
• two rare missense mutations in VANGL1, encoding a receptor involved in WNT/PCP signaling, may be associated with Adolescent Idiopathic Scoliosis (PMID:27755493)
• VANGL1 gene is not associated with Adolescent Idiopathic Scoliosis in the Chinese population (PMID:29189642)
• High KITENIN expression is associated with cholangiocarcinoma. (PMID:29366806)
• Circular RNA circ-VANGL1 is a competing endogenous RNA which contributes to bladder cancer progression by regulating miR-605-3p/VANGL1 pathway. (PMID:30146736)
• ErbB4/KITENIN-Mediated Signaling is Activated in Cetuximab-Resistant Colorectal Cancer Cells. (PMID:30360226)
• Circ-VANGL1 promotes the development of Osteoporosis via binding to miRNA-217 to downregulate RUNX2 expression. (PMID:30779060)
• Somatic mutations in planar cell polarity genes in neural tissue from human fetuses with neural tube defects. (PMID:32356230)
• Up-regulation of VANGL1 by IGF2BPs and miR-29b-3p attenuates the detrimental effect of irradiation on lung adenocarcinoma. (PMID:33228740)
• Knockdown of circular RNA VANGL1 inhibits TGF-beta-induced epithelial-mesenchymal transition in melanoma cells by sponging miR-150-5p. (PMID:34750955)
• Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease. (PMID:35028616)
• Myelomeningocele among Pakistani population. (PMID:35713047)
• Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations. (PMID:38669183)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vangl1	ENSDARG00000004305
mus_musculus	Vangl1	ENSMUSG00000027860
rattus_norvegicus	Vangl1	ENSRNOG00000016477
drosophila_melanogaster	Vang	FBGN0015838
caenorhabditis_elegans		WBGENE00015171

Paralogs (1): VANGL2 (ENSG00000162738)

Protein

Protein identifiers

Vang-like protein 1 — Q8TAA9 (reviewed: Q8TAA9)

Alternative names: Loop-tail protein 2 homolog, Strabismus 2, Van Gogh-like protein 1

All UniProt accessions (1): Q8TAA9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Heterodimer with VANGL2. Interacts through its C-terminal region with the N-terminal half of DVL1, DVL2 and DVL3. The PDZ domain of DVL1, DVL2 and DVL3 is required for the interaction.

Subcellular location. Cell membrane.

Tissue specificity. According to PubMed:11956595, ubiquitously expressed. According to PubMed:12011995, expressed specifically in testis and ovary.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Vang family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TAA9-1	1	yes
Q8TAA9-2	2

RefSeq proteins (3): NP_001165882, NP_001165883, NP_620409* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009539	VANGL	Family

Pfam: PF06638

UniProt features (62 total): helix 16, sequence variant 15, strand 9, turn 6, topological domain 5, transmembrane region 4, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9JK9	ELECTRON MICROSCOPY	2.2
9JK8	ELECTRON MICROSCOPY	2.6
8ZXD	ELECTRON MICROSCOPY	2.9
9JK6	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAA9-F1	76.02	0.38

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 86, 88

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle

MSigDB gene sets: 340 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_RESPIRATORY_SYSTEM_PROCESS, GOBP_PIGMENTATION, FISCHER_G2_M_CELL_CYCLE, GOBP_CILIUM_MOVEMENT, MODULE_301, LIAO_METASTASIS, TATA_C, AACTTT_UNKNOWN, ACTTTAT_MIR1425P, CUI_TCF21_TARGETS_2_DN

GO Biological Process (4): pigmentation (GO:0043473), Wnt signaling pathway, planar cell polarity pathway (GO:0060071), mucociliary clearance (GO:0120197), multicellular organism development (GO:0007275)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), lateral plasma membrane (GO:0016328), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	18

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
biological_process	1
non-canonical Wnt signaling pathway	1
respiratory system process	1
epithelial cilium movement involved in extracellular fluid movement	1
multicellular organismal process	1
anatomical structure development	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1

Protein interactions and networks

STRING

1238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VANGL1	DVL1	O14640	961
VANGL1	CELSR1	Q9NYQ6	958
VANGL1	PRICKLE2	Q7Z3G6	934
VANGL1	FZD6	O60353	933
VANGL1	SCRIB	Q14160	923
VANGL1	CD82	P27701	914
VANGL1	PRICKLE1	Q96MT3	906
VANGL1	DVL2	O14641	887
VANGL1	PTK7	Q13308	879
VANGL1	PRICKLE3	O43900	847
VANGL1	PRICKLE4	Q2TBC4	838
VANGL1	DVL3	Q92997	796
VANGL1	ANKRD6	Q9Y2G4	752
VANGL1	DACT1	Q9NYF0	713
VANGL1	RYK	P34925	711

IntAct

317 interactions, top by confidence:

A	B	Type	Score
INO80E	YY1	psi-mi:“MI:0914”(association)	0.900
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
INO80E	TFPT	psi-mi:“MI:0914”(association)	0.790
PNN	PRP4K	psi-mi:“MI:0914”(association)	0.790
PTPN3	VANGL1	psi-mi:“MI:0915”(physical association)	0.750
VANGL1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.750
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
EIF3L	EIF3F	psi-mi:“MI:0914”(association)	0.640
DLG1	VANGL1	psi-mi:“MI:0407”(direct interaction)	0.620
PNN	SAP18	psi-mi:“MI:0914”(association)	0.620
VANGL1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.620
PTPN3	ACOT8	psi-mi:“MI:0914”(association)	0.590
VANGL1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.590
VANGL1	CREB3	psi-mi:“MI:0915”(physical association)	0.560
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530

BioGRID (309): VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Proximity Label-MS), VANGL1 (Proximity Label-MS), VANGL1 (Proximity Label-MS), VANGL1 (Proximity Label-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GQX3, A0A1B0GRQ0, A0A1B0GVT2, A0A590UK83, A4QNL6, A5D7B5, A6H770, B3DHH5, E1BAR0, O75324, P0DKX4, P35803, P56695, P58511, P61807, P61808, P84889, Q12016, Q15053, Q17Q87, Q28793, Q2TZ20, Q3MHM8, Q4V786, Q4V921, Q4VBG5, Q56JY4, Q5RBD8, Q5U2S1, Q68FV2, Q6DGP4, Q6GLN5, Q758B5, Q80Z96, Q80ZU4, Q876Z1, Q8BH07, Q8BT42, Q8GUM4, Q8R0W6

Diamond homologs: P84889, Q4VBG5, Q80Z96, Q8TAA9, Q8UVJ6, Q90X64, Q90Z05, Q91ZD4, Q9ULK5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 227 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	7	27.2×	2e-06
SHC-mediated cascade:FGFR4	6	22.2×	4e-05
SHC-mediated cascade:FGFR3	5	20.4×	1e-04
SHC-mediated cascade:FGFR1	6	20.3×	4e-05
FRS-mediated FGFR4 signaling	6	20.3×	4e-05
SHC-mediated cascade:FGFR2	6	19.4×	5e-05
VEGFR2 mediated cell proliferation	5	19.4×	2e-04
FRS-mediated FGFR1 signaling	6	18.6×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
receptor clustering	5	15.8×	5e-03
establishment or maintenance of epithelial cell apical/basal polarity	5	14.7×	5e-03
regulation of postsynaptic membrane neurotransmitter receptor levels	5	12.5×	8e-03
cell surface receptor protein tyrosine kinase signaling pathway	8	7.0×	5e-03
MAPK cascade	8	6.2×	8e-03
cell-cell adhesion	10	5.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

301 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	167
Likely benign	12
Benign	40

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1027390	NM_138959.3(VANGL1):c.838del (p.Val279_Leu280insTer)	Pathogenic
1347	NM_138959.3(VANGL1):c.821G>A (p.Arg274Gln)	Likely pathogenic

SpliceAI

1630 predictions. Top by Δscore:

Variant	Effect	Δscore
1:115659765:G:GT	donor_gain	1.0000
1:115659771:CAG:C	donor_loss	1.0000
1:115659774:G:GG	donor_gain	1.0000
1:115659775:T:G	donor_loss	1.0000
1:115682360:TCAGT:T	acceptor_loss	1.0000
1:115682362:A:AG	acceptor_gain	1.0000
1:115682362:A:G	acceptor_loss	1.0000
1:115682363:G:GA	acceptor_gain	1.0000
1:115682363:GT:G	acceptor_gain	1.0000
1:115682363:GTAT:G	acceptor_gain	1.0000
1:115682494:GATG:G	donor_gain	1.0000
1:115682495:ATGGT:A	donor_loss	1.0000
1:115682498:G:GG	donor_gain	1.0000
1:115682499:T:G	donor_loss	1.0000
1:115683939:CAAA:C	acceptor_gain	1.0000
1:115683940:A:AG	acceptor_gain	1.0000
1:115683940:AAAG:A	acceptor_gain	1.0000
1:115683940:AAAGG:A	acceptor_gain	1.0000
1:115683941:A:G	acceptor_gain	1.0000
1:115683941:AAG:A	acceptor_gain	1.0000
1:115683941:AAGG:A	acceptor_gain	1.0000
1:115683942:A:AG	acceptor_gain	1.0000
1:115683942:AG:A	acceptor_gain	1.0000
1:115683942:AGG:A	acceptor_gain	1.0000
1:115683943:G:GT	acceptor_gain	1.0000
1:115683943:GG:G	acceptor_gain	1.0000
1:115683943:GGC:G	acceptor_gain	1.0000
1:115683943:GGCC:G	acceptor_gain	1.0000
1:115684054:C:T	donor_gain	1.0000
1:115684072:GCAAG:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000001230 (1:115657830 C>G,T), RS1000077655 (1:115649259 T>A,C), RS1000085671 (1:115670077 T>C), RS1000128227 (1:115648932 C>T), RS1000134913 (1:115686513 C>T), RS1000219499 (1:115647089 A>G), RS1000253502 (1:115675818 A>G), RS1000307752 (1:115693802 A>G), RS1000330959 (1:115693579 G>A,T), RS1000392615 (1:115660975 G>A), RS1000443502 (1:115660610 C>T), RS1000456270 (1:115686390 ATGCCATCAGGC>A), RS1000505720 (1:115686769 A>T), RS1000681737 (1:115655184 A>C), RS1000781339 (1:115657396 T>TA)

Disease associations

OMIM: gene MIM:610132 | disease phenotypes: MIM:182940, MIM:148300

GenCC curated gene-disease

Disease	Classification	Inheritance
neural tube defects, susceptibility to	Limited	Autosomal dominant
familial caudal dysgenesis	Limited	Autosomal dominant

Mondo (5): caudal regression sequence (MONDO:0017607), neural tube defects, susceptibility to (MONDO:0020705), neural tube defect (MONDO:0018075), keratoconus (MONDO:0015486), familial caudal dysgenesis (MONDO:0010831)

Orphanet (5): Caudal regression syndrome (Orphanet:3027), Neural tube defect (Orphanet:3388), Spina bifida and other spinal dysraphisms (Orphanet:823), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000011	Neurogenic bladder
HP:0000016	Urinary retention
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000062	Ambiguous genitalia
HP:0000069	Abnormality of the ureter
HP:0000073	Ureteral duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000086	Ectopic kidney
HP:0000104	Renal agenesis
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000822	Hypertension
HP:0000921	Missing ribs
HP:0000960	Sacral dimple
HP:0001012	Multiple lipomas
HP:0001287	Meningitis
HP:0001315	Reduced tendon reflexes
HP:0001387	Joint stiffness
HP:0001762	Talipes equinovarus
HP:0001776	Bilateral talipes equinovarus
HP:0002019	Constipation
HP:0002023	Anal atresia
HP:0002089	Pulmonary hypoplasia
HP:0002139	Arrhinencephaly
HP:0002144	Tethered cord
HP:0002308	Chiari malformation
HP:0002315	Headache

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003855_5	Gut microbiota (bacterial taxa)	5.000000e-08
GCST004862_165	Itch intensity from mosquito bite adjusted by bite size	6.000000e-06
GCST009462_22	Optic disc size	4.000000e-27
GCST009462_7	Optic disc size	4.000000e-23
GCST010866_18	Coronary artery disease	9.000000e-11
GCST011369_2	Iron status biomarkers (ferritin levels)	3.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004459	ferritin measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007640	Keratoconus	C11.204.627
D009436	Neural Tube Defects	C10.500.680; C16.131.666.680

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	3
sodium arsenite	increases expression	2
bisphenol S	affects expression, decreases methylation	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0SP	Ubigene HeLa VANGL1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01485211	PHASE4	COMPLETED	Corneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039	PHASE4	COMPLETED	Effect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853	PHASE4	COMPLETED	Epi-On Corneal Crosslinking for Keratoconus
NCT03429569	PHASE4	UNKNOWN	Cross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956	PHASE4	COMPLETED	Corneal Crosslinking Treatment Study
NCT07474870	PHASE4	NOT_YET_RECRUITING	Outcomes of CTAK Surgery
NCT00301587	PHASE3	WITHDRAWN	A Study to Evaluate Folate Levels in Women Taking Oral Contraceptives
NCT00468481	PHASE3	COMPLETED	Efficacy and Safety Study for an Oral Contraceptive Containing Folate
NCT00371202	PHASE3	UNKNOWN	Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus
NCT00647699	PHASE3	COMPLETED	Corneal Collagen Cross-linking for Progressive Keratoconus
NCT00815256	PHASE3	UNKNOWN	Safety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus
NCT00887900	PHASE3	COMPLETED	Deep Anterior Lamellar Keratoplasty (DALK)
NCT01112072	PHASE3	UNKNOWN	Corneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia
NCT01152541	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin
NCT01190306	PHASE3	TERMINATED	Safety Study of the VEGA UV-A System to Treat Keratoconus
NCT01344187	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01459679	PHASE3	TERMINATED	Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
NCT01464268	PHASE3	UNKNOWN	Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
NCT01604135	PHASE3	ACTIVE_NOT_RECRUITING	Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial
NCT01643226	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01672814	PHASE3	COMPLETED	Microwave Treatment and Corneal Collagen Crosslinking for Keratoconus
NCT01682993	PHASE3	TERMINATED	Corneal Cross Linking and Topography Guided Excimer Laser Treatment
NCT01972854	PHASE3	TERMINATED	Safety and Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT02613780	PHASE3	UNKNOWN	Refractive Treatment of Early Keratoconus
NCT02638376	PHASE3	UNKNOWN	Evaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus
NCT03080077	PHASE3	UNKNOWN	Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
NCT03187912	PHASE3	COMPLETED	Accelerated Corneal Cross-linking With Different Riboflavin Solutions
NCT03442751	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Epi-on Corneal Cross-linking in Eyes With Progressive Keratoconus
NCT03858036	PHASE3	UNKNOWN	Corneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders
NCT04897503	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Riboflavin/Dextran or Riboflavin/Methylcellulose
NCT04905108	PHASE3	UNKNOWN	Transepithelial (Epi-on) Corneal Collagen Crosslinking to Treat Keratoconus and Corneal Ectasia
NCT05027295	PHASE3	UNKNOWN	Accelerated Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Pulse or Continuous UV-A Light
NCT06100939	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06100952	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age with Keratoconus
NCT06450470	PHASE3	RECRUITING	Use of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT07124910	PHASE3	RECRUITING	Comparison of Epi-ON Corneal Collagen Crosslinking Performed Using an 18-Minute UVA Exposure vs. a 24-Minute UVA Exposure on Eyes With Ectatic Corneal Diseases
NCT07135167	PHASE3	RECRUITING	Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome
NCT01392989	PHASE2	COMPLETED	Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
NCT00409955	PHASE2	COMPLETED	Lamellar Transplant With Lyophilized Corneas