Neural tube defects, susceptibility to

Summary

Neural tube defects, susceptibility to (MONDO:0020705) is a disease caused by AMBRA1 (GenCC Strong), with 7 cohort genes and 29 clinical trials. Top therapeutic interventions include drospirenone, ethinyl estradiol, and inositol.

At a glance

• Causal gene: AMBRA1 (GenCC Strong)
• Cohort genes: 7
• ClinVar variants: 22
• Clinical trials: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neural tube defects, susceptibility to
Mondo ID	MONDO:0020705
OMIM	182940
UMLS	C3891448
MedGen	856010
Is cancer (heuristic)	no

Also known as: neural tube defects · NTD · spina bifida, susceptibility to

Data availability: 22 ClinVar variants · 12 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › neural tube defects, susceptibility to

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 9 risk factor, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1347	NM_138959.3(VANGL1):c.821G>A (p.Arg274Gln)	VANGL1	Likely pathogenic	criteria provided, single submitter
183426	NM_001378328.1(CELSR1):c.5052_5053dup (p.Glu1685fs)	CELSR1	risk factor	no assertion criteria provided
183427	NM_001378328.1(CELSR1):c.5723_5724del (p.Val1908fs)	CELSR1	risk factor	no assertion criteria provided
31934	NM_025129.5(FUZ):c.115C>T (p.Pro39Ser)	FUZ	risk factor	no assertion criteria provided
31935	NM_025129.5(FUZ):c.1060G>T (p.Asp354Tyr)	FUZ	risk factor	no assertion criteria provided
31936	NM_025129.5(FUZ):c.1211G>A (p.Arg404Gln)	FUZ	risk factor	no assertion criteria provided
8181	NM_001366285.2(TBXT):c.1037+79C>T	TBXT	risk factor	no assertion criteria provided
1348	NM_138959.3(VANGL1):c.983T>C (p.Met328Thr)	VANGL1	risk factor	no assertion criteria provided
9052	NM_020335.3(VANGL2):c.1057C>T (p.Arg353Cys)	VANGL2	risk factor	no assertion criteria provided
9053	NM_020335.3(VANGL2):c.1310T>C (p.Phe437Ser)	VANGL2	risk factor	no assertion criteria provided
3382639	NM_138959.3(VANGL1):c.557G>A (p.Arg186His)	VANGL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892704	NM_025129.5(FUZ):c.354C>G (p.Ile118Met)	FUZ	Uncertain significance	criteria provided, single submitter
1334511	NM_001366285.2(TBXT):c.640G>T (p.Ala214Ser)	TBXT	Uncertain significance	criteria provided, multiple submitters, no conflicts
2546398	NM_001366285.2(TBXT):c.800G>A (p.Gly267Asp)	TBXT	Uncertain significance	criteria provided, multiple submitters, no conflicts
3324124	NM_001366285.2(TBXT):c.1178C>T (p.Ala393Val)	TBXT	Uncertain significance	criteria provided, multiple submitters, no conflicts
183430	NM_138959.3(VANGL1):c.542G>A (p.Arg181Gln)	VANGL1	Uncertain significance	criteria provided, single submitter
3892831	NM_138959.3(VANGL1):c.1337G>A (p.Ser446Asn)	VANGL1	Uncertain significance	criteria provided, single submitter
3892832	NM_138959.3(VANGL1):c.1460A>G (p.Asp487Gly)	VANGL1	Uncertain significance	criteria provided, single submitter
2438509	NM_020335.3(VANGL2):c.986C>T (p.Ala329Val)	VANGL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2690436	NM_020335.3(VANGL2):c.233C>T (p.Thr78Ile)	VANGL2	Uncertain significance	criteria provided, single submitter
3391214	NM_020335.3(VANGL2):c.1298C>T (p.Thr433Met)	VANGL2	Uncertain significance	criteria provided, single submitter
3892833	NM_020335.3(VANGL2):c.746A>T (p.Lys249Met)	VANGL2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
AMBRA1	Strong	Autosomal dominant	neural tube defects, susceptibility to
CELSR1	Moderate	Autosomal dominant	neural tube defects, susceptibility to	6
VANGL2	Moderate	Autosomal dominant	neural tube defects, susceptibility to	4
FUZ	Limited	Unknown	neural tube defects, susceptibility to	3
VANGL1	Limited	Autosomal dominant	neural tube defects, susceptibility to	3
CCL2	No Known Disease Relationship	Autosomal dominant	neural tube defects, susceptibility to

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VANGL2	Orphanet:563609	Isolated anencephaly
VANGL2	Orphanet:563612	Isolated exencephaly
VANGL1	Orphanet:3027	Caudal regression syndrome
CELSR1	Orphanet:569816	CELSR1-related late-onset primary lymphedema
FUZ	Orphanet:3027	Caudal regression syndrome
FUZ	Orphanet:620158	Non-syndromic non-specific multisutural craniosynostosis
TBXT	Orphanet:178	Chordoma
TBXT	Orphanet:397927	Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VANGL2	HGNC:15511	ENSG00000162738	Q9ULK5	Vang-like protein 2	gencc,clinvar
VANGL1	HGNC:15512	ENSG00000173218	Q8TAA9	Vang-like protein 1	gencc,clinvar
CELSR1	HGNC:1850	ENSG00000075275	Q9NYQ6	Cadherin EGF LAG seven-pass G-type receptor 1	gencc,clinvar
FUZ	HGNC:26219	ENSG00000010361	Q9BT04	Protein fuzzy homolog	gencc,clinvar
CCL2	HGNC:10618	ENSG00000108691	P13500	C-C motif chemokine 2	gencc
AMBRA1	HGNC:25990	ENSG00000110497	Q9C0C7	Activating molecule in BECN1-regulated autophagy protein 1	gencc
TBXT	HGNC:11515	ENSG00000164458	O15178	T-box transcription factor T	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VANGL2	Vang-like protein 2	Involved in the control of early morphogenesis and patterning of both axial midline structures and the development of neural plate.
CELSR1	Cadherin EGF LAG seven-pass G-type receptor 1	Receptor that may have an important role in cell/cell signaling during nervous system formation.
FUZ	Protein fuzzy homolog	Probable planar cell polarity effector involved in cilium biogenesis.
CCL2	C-C motif chemokine 2	Acts as a ligand for C-C chemokine receptor CCR2.
AMBRA1	Activating molecule in BECN1-regulated autophagy protein 1	Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy.
TBXT	T-box transcription factor T	Involved in the transcriptional regulation of genes required for mesoderm formation and differentiation.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.14

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
GPCR	1	3.4×	0.626
Scaffold/PPI	1	2.5×	0.626
Transcription factor	1	1.2×	0.626
Other/Unknown	4	1.0×	0.626

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VANGL2	Other/Unknown	no		VANGL
VANGL1	Other/Unknown	no		VANGL
CELSR1	GPCR	yes		EGF-type_Asp/Asn_hydroxyl_site, GPS, EGF
FUZ	Other/Unknown	no		Fuzzy, FUZ/MON1/HPS1_longin_3, FUZ/MON1/HPS1_longin_2
CCL2	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
AMBRA1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TBXT	Transcription factor	no		TF_T-box, TF_Brachyury, p53-like_TF_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

7 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
bronchial epithelial cell	2
buccal mucosa cell	1
ganglionic eminence	1
caput epididymis	1
corpus epididymis	1
lower esophagus mucosa	1
left testis	1
right testis	1
right uterine tube	1
gall bladder	1
islet of Langerhans	1
vena cava	1
cervix squamous epithelium	1
oocyte	1
secondary oocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
pancreatic ductal cell	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VANGL2	210	broad	marker	ganglionic eminence, buccal mucosa cell, ventricular zone
VANGL1	234	ubiquitous	marker	bronchial epithelial cell, corpus epididymis, caput epididymis
CELSR1	224	ubiquitous	marker	ventricular zone, lower esophagus mucosa, bronchial epithelial cell
FUZ	243	ubiquitous	marker	right uterine tube, right testis, left testis
CCL2	252	ubiquitous	marker	vena cava, gall bladder, islet of Langerhans
AMBRA1	279	ubiquitous	marker	oocyte, secondary oocyte, cervix squamous epithelium
TBXT	42	tissue_specific	marker	primordial germ cell in gonad, pancreatic ductal cell, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCL2	5,749
AMBRA1	4,380
VANGL1	1,864
VANGL2	1,763
CELSR1	1,166
TBXT	1,028
FUZ	417

Intra-cohort edges

A	B	Sources
CELSR1	VANGL1	string_interaction
CELSR1	VANGL2	string_interaction
VANGL1	VANGL2	biogrid_interaction

Structural data

PDB: 7 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBXT	O15178	56
CCL2	P13500	14
VANGL2	Q9ULK5	7
VANGL1	Q8TAA9	4
FUZ	Q9BT04	3
CELSR1	Q9NYQ6	2
AMBRA1	Q9C0C7	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. Enrichment computed across 7 evidence-associated genes (6 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RND1 GTPase cycle	2	88.5×	0.004	VANGL2, VANGL1
RND3 GTPase cycle	2	86.5×	0.004	VANGL2, VANGL1
RND2 GTPase cycle	2	86.5×	0.004	VANGL2, VANGL1
NFE2L2 regulating inflammation associated genes	1	380.7×	0.033	CCL2
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	237.9×	0.043	TBXT
PERK regulates gene expression	1	135.9×	0.050	CCL2
Formation of axial mesoderm	1	135.9×	0.050	TBXT
Formation of definitive endoderm	1	119.0×	0.050	TBXT
Germ layer formation at gastrulation	1	112.0×	0.050	TBXT
Cardiogenesis	1	70.5×	0.058	TBXT
ATF4 activates genes in response to endoplasmic reticulum stress	1	68.0×	0.058	CCL2
Formation of paraxial mesoderm	1	68.0×	0.058	TBXT
Unfolded Protein Response (UPR)	1	59.5×	0.058	CCL2
Nuclear events mediated by NFE2L2	1	56.0×	0.058	CCL2
RHOH GTPase cycle	1	51.4×	0.058	VANGL1
PCP/CE pathway	1	50.1×	0.058	VANGL2
RHOV GTPase cycle	1	47.6×	0.058	VANGL1
RHOU GTPase cycle	1	46.4×	0.058	VANGL1
RHOF GTPase cycle	1	43.3×	0.058	VANGL1
Gastrulation	1	43.3×	0.058	TBXT
Interleukin-10 signaling	1	38.8×	0.062	CCL2
Asymmetric localization of PCP proteins	1	34.0×	0.063	VANGL2
RHOD GTPase cycle	1	34.0×	0.063	VANGL1
RHOJ GTPase cycle	1	33.4×	0.063	VANGL1
Chemokine receptors bind chemokines	1	31.2×	0.063	CCL2
RHOQ GTPase cycle	1	30.2×	0.063	VANGL1
Hedgehog ‘off’ state	1	29.7×	0.063	FUZ
RHOB GTPase cycle	1	25.7×	0.066	VANGL1
RHOG GTPase cycle	1	24.7×	0.066	VANGL1
Autophagy	1	24.7×	0.066	AMBRA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment of planar polarity	3	451.4×	3e-06	VANGL2, CELSR1, FUZ
orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis	2	1605.0×	1e-05	VANGL2, CELSR1
planar dichotomous subdivision of terminal units involved in lung branching morphogenesis	2	1605.0×	1e-05	VANGL2, CELSR1
lateral sprouting involved in lung morphogenesis	2	1605.0×	1e-05	VANGL2, CELSR1
Wnt signaling pathway, planar cell polarity pathway	3	195.2×	1e-05	VANGL2, VANGL1, CELSR1
establishment of body hair planar orientation	2	963.0×	3e-05	VANGL2, CELSR1
neural tube closure	3	80.2×	1e-04	VANGL2, CELSR1, FUZ
apical protein localization	2	283.2×	3e-04	VANGL2, CELSR1
neural tube development	2	150.5×	0.001	FUZ, AMBRA1
hair follicle development	2	109.4×	0.002	VANGL2, FUZ
non-motile cilium assembly	2	83.0×	0.003	VANGL2, FUZ
helper T cell extravasation	1	2407.4×	0.003	CCL2
cell migration involved in kidney development	1	2407.4×	0.003	VANGL2
chemokine (C-C motif) ligand 2 signaling pathway	1	2407.4×	0.003	CCL2
negative regulation of neural crest formation	1	2407.4×	0.003	FUZ
Rho protein signal transduction	2	70.8×	0.003	VANGL2, CELSR1
establishment of planar polarity involved in neural tube closure	1	1203.7×	0.005	VANGL2
positive regulation of free ubiquitin chain polymerization	1	1203.7×	0.005	AMBRA1
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	1203.7×	0.005	FUZ
negative regulation of natural killer cell chemotaxis	1	1203.7×	0.005	CCL2
regulation of actin cytoskeleton organization	2	45.0×	0.005	VANGL2, CELSR1
convergent extension involved in neural plate elongation	1	802.5×	0.007	VANGL2
dopaminergic neuron axon guidance	1	802.5×	0.007	VANGL2
serotonergic neuron axon guidance	1	802.5×	0.007	VANGL2
protein localization involved in establishment of planar polarity	1	802.5×	0.007	CELSR1
establishment of planar polarity of embryonic epithelium	1	601.9×	0.008	CELSR1
negative regulation of neuron apoptotic process	2	31.7×	0.008	CCL2, AMBRA1
muscular septum morphogenesis	1	481.5×	0.009	VANGL2
convergent extension involved in axis elongation	1	481.5×	0.009	VANGL2
negative regulation of vascular endothelial cell proliferation	1	481.5×	0.009	CCL2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 2 of 7 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCL2	2	3
VANGL2	0	0
VANGL1	0	0
CELSR1	0	0
FUZ	0	0
AMBRA1	0	0
TBXT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FASUDIL	3	CCL2
AZD-5153	1	CCL2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CCL2	24	Binding:24
TBXT	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FASUDIL	3	CCL2
AZD-5153	1	CCL2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	CCL2
C	Druggable family + PDB, no drug	1	CELSR1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	VANGL2, VANGL1, FUZ, AMBRA1, TBXT

Undrugged target profiles

6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
VANGL2	0	—
VANGL1	0	—
CELSR1	0	—
FUZ	0	—
AMBRA1	0	—
TBXT	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 29.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	24
PHASE3	2
PHASE1	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
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
NCT01392989	PHASE2	COMPLETED	Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
NCT03794011	PHASE1	ACTIVE_NOT_RECRUITING	Patch vs. No Patch Fetoscopic Meningomyelocele Repair Study
NCT00452829	PHASE1	COMPLETED	Prevention of Neural Tube Defects by Inositol in Conjunction With Folic Acid (PONTI Study)
NCT03090633	Not specified	ACTIVE_NOT_RECRUITING	Fetoscopic Repair of Isolated Fetal Spina Bifida
NCT03856034	Not specified	RECRUITING	Laparotomy Versus Percutaneous Endoscopic Correction of Myelomeningocele
NCT04362592	Not specified	ACTIVE_NOT_RECRUITING	In-Utero Endoscopic Correction of Spina Bifida
NCT04770805	Not specified	ACTIVE_NOT_RECRUITING	In Utero Fetoscopic Repair Program for Sacral Myelomeningoceles and Mye-LDM
NCT05672849	Not specified	RECRUITING	Safety and Efficacy of Devices Used in Fetoscopic Neural Tube Defect Repair Cases
NCT06734611	Not specified	NOT_YET_RECRUITING	Folic Acid Salt Study (FISFA Zambia)
NCT06946563	Not specified	RECRUITING	Fetoscopic Neural Tube Defect Repair
NCT00341068	Not specified	TERMINATED	Genetic Analysis of Neural Tube and Orofacial Cleft Defects in the Irish Population
NCT00394862	Not specified	COMPLETED	Efficacy of Weekly Versus Daily Folic Acid Supplementation
NCT01244399	Not specified	COMPLETED	Influence of Espresso on Adsorption of Myo-inositol
NCT01253746	Not specified	UNKNOWN	Genetics of Neural Tube Defects
NCT01743196	Not specified	COMPLETED	Folate Metabolism in Normal Weight and Obese Women of Child-bearing Age
NCT03315637	Not specified	UNKNOWN	Fetal Endoscopic Surgery for Spina Bifida
NCT03936322	Not specified	COMPLETED	Minimally Invasive Fetoscopic Regenerative Repair of Spina Bifida - A Pilot Study
NCT04135274	Not specified	COMPLETED	Is Neutrophil to Lymphocyte Ratio a Prognostic Factor of Sepsis in Newborns With Operated Neural Tube Defects?
NCT04140669	Not specified	TERMINATED	Automated Myocardial Performance Index Using Samsung HERA W10
NCT04523233	Not specified	UNKNOWN	Metals/Vitamins Levels in NTD
NCT04760509	Not specified	UNKNOWN	Short- Term Follow up Of Neonates Born With Neural Tube Defect
NCT05454085	Not specified	COMPLETED	Could Bisphenol-A Have a Role in the Etiology of Neural Tube Defects
NCT05883761	Not specified	COMPLETED	Birth Outcomes In Eswatini After Transition To Dolutegravir-Based Treatment
NCT05935631	Not specified	COMPLETED	Feasibility, Acceptability and Directional Signal Effect on Blood Folate Levels of Iodized Salt Fortified With Folic Acid: Clinical Study
NCT06135883	Not specified	COMPLETED	Assessing Folic Acid in High-Risk Pregnancy for Neural Tube Defects
NCT06174883	Not specified	COMPLETED	Salt-FA to Increase Folate Levels
NCT06904612	Not specified	COMPLETED	Using Iodized Salt to Improve Serum Folate, B12 and Iron Levels

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DROSPIRENONE	4	1
ETHINYL ESTRADIOL	4	1
INOSITOL	3	2
IODINE	3	1
BISPHENOL A	0	2
CHEMBL1078369	0	1