Spina bifida

disease
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Also known as neural tube defects, susceptibility toNTDrachischisisspina bifida (disease)spinal meningocelespinal myelocelespinal myelomeningocele

Summary

Spina bifida (MONDO:0008449) is a disease with 1 cohort gene (3 GWAS associations across 3 studies) and 102 clinical trials. Top therapeutic interventions include oxybutynin chloride and pamidronic acid.

At a glance

  • Cohort genes: 1
  • GWAS associations: 3
  • Clinical trials: 102

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namespina bifida
Mondo IDMONDO:0008449
EFOEFO:0003105
MeSHD016135
DOIDDOID:0080016
ICD-10-CMQ05
ICD-112036217905
NCITC101214
SNOMED CT67531005
UMLSC0080178
MedGen38283
Is cancer (heuristic)no

Also known as: neural tube defects, susceptibility to · NTD · rachischisis · spina bifida · spina bifida (disease) · spinal meningocele · spinal myelocele · spinal myelomeningocele

Data availability: 3 GWAS associations (3 studies) · 1 GenCC gene-disease record · 1 HPO phenotype · 6 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disordercongenital nervous system disorderspina bifida

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Subtypes (2): spina bifida occulta, isolated spina bifida

Genetics & variants

GWAS landscape

3 GWAS associations across 3 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs754266527e-14LHPPA
rs455800334e-10ASB2A
rs1401998002e-07SULT1C2A

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90474255UK Biobank Whole-Genome Sequencing Consortium2025387458,053Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90436766Zhou W2018210408,394Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90566547Tindula G2024650Genome-wide analysis of spina bifida risk variants in a case-control study from Bangladesh.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding3
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic0

MAF distribution

BucketVariants
common (>=0.05)1
low_freq (0.01-0.05)0
rare (<0.01)0
unknown2

Functional consequences

ConsequenceCount
missense_variant2
stop_gained1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs7542665210124461954C>A,G,T0.05missense_variantLHPP7e-14Tier 1: coding
rs455800331493964365G>A,C,Tmissense_variantASB24e-10Tier 1: coding
rs1401998002108293753G>Astop_gainedSULT1C22e-07Tier 1: coding

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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.

GeneClassificationInheritanceDiseaseRecords
FKBP8ModerateAutosomal dominantspina bifida

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
FKBP8HGNC:3724ENSG00000105701Q14318Peptidyl-prolyl cis-trans isomerase FKBP8gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
FKBP8Peptidyl-prolyl cis-trans isomerase FKBP8Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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.

FamilyGenesFoldFDR
Enzyme (other)112.0×0.083

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
FKBP8Enzyme (other)yes5.2.1.8PPIase_FKBP_dom, TPR-like_helical_dom_sf, TPR_rpt

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
left testis1
right frontal lobe1
right testis1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
FKBP8253ubiquitousmarkerright frontal lobe, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
FKBP84,491

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
FKBP8Q143186

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Ub-specific processing proteases153.1×0.019FKBP8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
protein localization to mitochondrion11296.3×0.005FKBP8
regulation of mitophagy11203.7×0.005FKBP8
dorsal/ventral neural tube patterning1802.5×0.005FKBP8
neuron fate specification1702.2×0.005FKBP8
negative regulation of protein phosphorylation1581.1×0.005FKBP8
positive regulation of BMP signaling pathway1455.5×0.005FKBP8
camera-type eye development1358.6×0.006FKBP8
BMP signaling pathway1200.6×0.009FKBP8
smoothened signaling pathway1181.2×0.009FKBP8
multicellular organism growth1137.0×0.011FKBP8
protein folding1103.4×0.013FKBP8
regulation of gene expression183.4×0.015FKBP8
intracellular signal transduction138.1×0.030FKBP8
negative regulation of apoptotic process134.8×0.031FKBP8
apoptotic process128.7×0.035FKBP8

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
FKBP800

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
FKBP82Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
FKBP85.2.1.8peptidylprolyl isomerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1FKBP8
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
FKBP82

Clinical trials & evidence

Clinical trials

Clinical trials: 102.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified99
PHASE22
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07027020PHASE3RECRUITINGEfficacy of Intravesical Oxybutynin in Children With Neurogenic Bladder Dysfunction
NCT00359775PHASE2COMPLETEDCoping Skills Training (CST) for Children With Chronic Health Conditions
NCT00378664PHASE2COMPLETEDLumbar to Sacral Ventral Nerve Re-Routing
NCT00891891Not specifiedACTIVE_NOT_RECRUITINGPsychosocial Adjustment of Adolescents With Spina Bifida
NCT02592291Not specifiedRECRUITINGMobile Health Self-Management and Support System for Chronic and Complex Health Conditions
NCT03090633Not specifiedACTIVE_NOT_RECRUITINGFetoscopic Repair of Isolated Fetal Spina Bifida
NCT03410667Not specifiedACTIVE_NOT_RECRUITINGIncontinence and Quality of Life in Children With Spina Bifida
NCT03698721Not specifiedNOT_YET_RECRUITINGUrothelium Tissue Engineering Using Biopsies From Transurethral Resection of Prostate
NCT03856034Not specifiedRECRUITINGLaparotomy Versus Percutaneous Endoscopic Correction of Myelomeningocele
NCT04243889Not specifiedACTIVE_NOT_RECRUITINGFetoscopic NEOX Cord 1K® Spina Bifida Repair
NCT04362592Not specifiedACTIVE_NOT_RECRUITINGIn-Utero Endoscopic Correction of Spina Bifida
NCT04770805Not specifiedACTIVE_NOT_RECRUITINGIn Utero Fetoscopic Repair Program for Sacral Myelomeningoceles and Mye-LDM
NCT05117827Not specifiedACTIVE_NOT_RECRUITINGPediatric Powered Wheelchair Standing Devices: An Exploratory Study
NCT05253196Not specifiedNOT_YET_RECRUITINGEnema Device for Children With Spina Bifida
NCT05339932Not specifiedACTIVE_NOT_RECRUITINGGrand Valley State University (GVSU) Skills on Wheels
NCT05726591Not specifiedRECRUITINGEvaluating Long-term Use of a Pediatric Robotic Exoskeleton (P.REX/Agilik) to Improve Gait in Children With Movement Disorders
NCT05784285Not specifiedNOT_YET_RECRUITINGDownstream Effects of Personalized ‘Top-down’ Participation-based Interventions Among Youth With Physical Disabilities
NCT05849285Not specifiedRECRUITINGEvaluation of the Transitional and Lifelong Care Program
NCT06025734Not specifiedRECRUITINGTranscutaneous Tibial Nerve Stimulation (TTNS) Treatment in Spina Bifida Pediatric Patients With Neurogenic Bladder
NCT06041334Not specifiedRECRUITINGEvaluation of muLtimodal and Non-invasive SPINa Bifida Neurovessels During Prospective Follow-up
NCT06419049Not specifiedRECRUITINGImpact of Standing Programs in Children With Spina Bifida: A Single Subject Design
NCT06618378Not specifiedNOT_YET_RECRUITINGEffectiveness of Biofeedback Training in Children with Neurogenic Bladder and Bowel Disorder Wıth Spina Bifida
NCT06723951Not specifiedRECRUITINGQUALAS Validation in Dutch
NCT06802770Not specifiedACTIVE_NOT_RECRUITINGEvaluation of Depression and Anxiety Levels of Parents of Children with Spina Bifida
NCT06828653Not specifiedRECRUITINGComparing Digitally and Traditionally Made Ankle Foot Orthoses
NCT06918119Not specifiedRECRUITINGTranscutaneous Spinal Stimulation for Children and Youth With Spina Bifida
NCT06929572Not specifiedRECRUITINGAutologous Human Umbilical Cord Tissue Patch for Postnatal Closure of Open Neural Tube Defects
NCT06946563Not specifiedRECRUITINGFetoscopic Neural Tube Defect Repair
NCT07178873Not specifiedRECRUITINGPsychosocial Teleassistance Programme for Adults With Spina Bifida
NCT07290556Not specifiedNOT_YET_RECRUITINGEstablishing the Preliminary Utility of a Novel Pediatric Manual Mobile Standing Wheelchair
NCT07390318Not specifiedRECRUITINGBowel Continence Across the Lifespan in People With Spina Bifida
NCT07531862Not specifiedNOT_YET_RECRUITINGSpina Bifida Healthcare Navigator Program
NCT07615686Not specifiedRECRUITINGtSCS in Children With Spina Bifida
NCT00031122Not specifiedUNKNOWNStudy of Genetic Risk Factors for Spina Bifida and Anencephaly
NCT00655681Not specifiedCOMPLETEDPrevention of Post Operative Bone Loss in Children
NCT00720161Not specifiedCOMPLETEDMetformin in Children With Motor Deficit
NCT00866112Not specifiedCOMPLETEDA Randomized Exercise Trial for Wheelchair Users
NCT00951509Not specifiedCOMPLETEDVirtual Reality Based Testing of Power Wheelchair Driving Skills
NCT01096459Not specifiedWITHDRAWNNerve Rerouting Treatment for Neurogenic Bladder in Spina Bifida
NCT01133288Not specifiedTERMINATEDYulex Glove Prospective Study in Spina Bifida

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
OXYBUTYNIN CHLORIDE41
PAMIDRONIC ACID41