Mendelian neurodevelopmental disorder

Summary

Mendelian neurodevelopmental disorder (MONDO:0100500) is a disease (an umbrella term covering 276 Mondo subtypes) caused by variants in ATXN7L3 and FAM177A1, with 3 cohort genes.

At a glance

• Causal genes: ATXN7L3 (GenCC Strong), FAM177A1 (GenCC Strong)
• Umbrella term: 276 Mondo subtypes
• Cohort genes: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Mendelian neurodevelopmental disorder
Mondo ID	MONDO:0100500
Is cancer (heuristic)	no

Data availability: 3 GenCC gene-disease records.

Disease family

An umbrella term covering 276 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder

Related subtypes (263): leukoencephalopathy, megalencephalic, epilepsy, familial adult myoclonic, encephalopathy, acute, infection-induced, GLUT1 deficiency syndrome, paraganglioma, familial hemiplegic migraine, stutter disorder, specific language impairment, anencephaly, complex cortical dysplasia with other brain malformations, familial periodic paralysis, tuberous sclerosis, essential tremor, intracranial extraskeletal myxoid chondrosarcoma, Parkinson disease, progressive external ophthalmoplegia, myalgic encephalomeyelitis/chronic fatigue syndrome, cerebral amyloid angiopathy, congenital nystagmus, Angelman syndrome, nevoid basal cell carcinoma syndrome, Chiari malformation type I, choreoathetosis, familial inverted, cluster headache, familial, coloboma of optic nerve, craniosynostosis-Dandy-Walker malformation-hydrocephalus syndrome, major affective disorder 1, neurohypophyseal diabetes insipidus, Duane retraction syndrome, lateral meningocele syndrome, encephalopathy, recurrent, of childhood, familial congenital palsy of trochlear nerve, Gerstmann-Straussler-Scheinker syndrome, Tourette syndrome, Guillain-Barre syndrome, familial, Frey syndrome, melanoma and neural system tumor syndrome, narcolepsy 1, linear nevus sebaceous syndrome, oculocerebrocutaneous syndrome, obsessive-compulsive disorder, paroxysmal extreme pain disorder, familial pterygium of the conjunctiva, retinal detachment, Sturge-Weber syndrome, DiGeorge syndrome, blue color blindness, velocardiofacial syndrome, von Hippel-Lindau disease, arthrogryposis, Chiari malformation type II, Behr syndrome, isolated cerebellar hypoplasia/agenesis, bilateral striopallidodentate calcinosis, Griscelli syndrome type 1, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, Riley-Day syndrome, glutaryl-CoA dehydrogenase deficiency, normal pressure hydrocephalus, hyperlexia, Johanson-Blizzard syndrome, macrocephaly/megalencephaly syndrome, autosomal recessive, neurocutaneous melanocytosis, myosclerosis, Bailey-Bloch congenital myopathy, choroid plexus papilloma, pyridoxine-dependent epilepsy, NPHP3-related Meckel-like syndrome, familial hemophagocytic lymphohistiocytosis type 1, mismatch repair cancer syndrome 1, orofaciodigital syndrome type 6, X-linked immunoneurologic disorder, HSD10 mitochondrial disease, rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked, severe neonatal-onset encephalopathy with microcephaly, dilated cardiomyopathy 3B, red-green color blindness, red color blindness, iris hypoplasia with glaucoma, major affective disorder 2, band heterotopia of brain, Brody myopathy, chorea, remitting, with nystagmus and cataract, isolated hereditary congenital facial paralysis, childhood apraxia of speech, megalencephaly-capillary malformation-polymicrogyria syndrome, familial infantile myoclonic epilepsy, TH-deficient dopa-responsive dystonia, glycine encephalopathy, spongiform encephalopathy with neuropsychiatric features, bilateral frontoparietal polymicrogyria, B4GALT1-congenital disorder of glycosylation, angioid streaks, familial meningioma, biotin-responsive basal ganglia disease, anxiety, rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome, specific phobia, bradyopsia, endogenous depression, narcolepsy 3, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, myofibrillar myopathy 5, major affective disorder 3, achromatopsia 6, pyridoxal phosphate-responsive seizures, prosopagnosia, hereditary, brain-lung-thyroid syndrome, polyhydramnios, megalencephaly, and symptomatic epilepsy, major affective disorder 4, major affective disorder 5, major affective disorder 6, major affective disorder 8, major affective disorder 7, major affective disorder 9, age-related hearing impairment 1, bilateral parasagittal parieto-occipital polymicrogyria, age-related hearing impairment 2, combined pituitary hormone deficiencies, genetic form, cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome, rhabdoid tumor predisposition syndrome 2, infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly, schizophrenia 15, schizophrenia 16, occipital pachygyria and polymicrogyria, familial retinal arterial macroaneurysm, narcolepsy 7, bilateral generalized polymicrogyria, myoclonus, familial, familial hyperprolactinemia, proximal myopathy with extrapyramidal signs, sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome, polymicrogyria, bilateral perisylvian, autosomal recessive, ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome, cerebellar-facial-dental syndrome, myopathy due to calsequestrin and SERCA1 protein overload, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, Brown syndrome, epilepsy with myoclonic atonic seizures, polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, hypermanganesemia with dystonia 2, aniridia 2, aniridia 3, severe congenital nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, myopic macular degeneration, 2-hydroxyglutaric aciduria, benign neonatal seizures, qualitative or quantitative defects of alpha-sarcoglycan, qualitative or quantitative defects of beta-sarcoglycan, qualitative or quantitative defects of gamma-sarcoglycan, qualitative or quantitative defects of delta-sarcoglycan, neuromuscular disease caused by qualitative or quantitative defects of dysferlin, caveolinopathy, neuromuscular disease caused by qualitative or quantitative defects of perlecan, neuromuscular disease caused by qualitative or quantitative defects of TRIM32, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, qualitative or quantitative defects of desmin, neuromuscular disease caused by qualitative or quantitative defects of telethonin, neuromuscular disease caused by qualitative or quantitative defects of beta-myosin heavy chain (MYH7), neuromuscular disease caused by qualitative or quantitative defects of plectin, spastic quadriplegic cerebral palsy, congenital stationary night blindness, holoprosencephaly, congenital hydrocephalus, intracranial berry aneurysm, familial congenital mirror movements, Moebius syndrome-axonal neuropathy-hypogonadotropic hypogonadism syndrome, Moyamoya disease, familial Alzheimer-like prion disease, phakomatosis pigmentokeratotica, benign familial infantile epilepsy, inborn aminoacylase deficiency, familial partial epilepsy, familial isolated pituitary adenoma, Hoyeraal-Hreidarsson syndrome, hereditary retinoblastoma, familial syringomyelia, PrP systemic amyloidosis, Prader-Willi-like syndrome, bilirubin encephalopathy, microcephaly-complex motor and sensory axonal neuropathy syndrome, undetermined early-onset epileptic encephalopathy, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, familial schizencephaly, lissencephaly spectrum disorders, Li-Fraumeni syndrome, multiminicore myopathy, parietal foramina, Ritscher-Schinzel syndrome, inherited retinal dystrophy, folinic acid-responsive seizures, megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome, nonsyndromic genetic hearing loss, progressive myoclonus epilepsy, pontocerebellar hypoplasia, cerebral lipidosis with dementia, inherited vitreoretinopathy, periventricular nodular heterotopia, PEHO-like syndrome, familial porencephaly, X-linked deafness, hereditary progressive chorea without dementia, hereditary hyperekplexia, neurofibromatosis, inherited orthostatic hypotension, auditory neuropathy, retinal ciliopathy, Behrens Baumann dust syndrome, inherited reflex epilepsy, inherited neurodegenerative disorder, febrile seizures, familial, 11, famililal cerebral cavernous malformations, familial panic disorder, microangiopathy and leukoencephalopathy, pontine, autosomal dominant, schizophrenia 19, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, cathepsin a-related arteriopathy-strokes-leukoencephalopathy, parkinsonism with polyneuropathy, central nervous system lupus, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, inherited dystonia, encephalopathy due to mitochondrial and peroxisomal fission defect, alpha-actinopathy, dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive, TPM3-related myopathy, Uner Tan Syndrome, TUBB3-related tubulinopathy, TTN-related myopathy, TPM2-related myopathy, fatty acyl-CoA reductase 1 upregulation, hereditary ataxia, brain malformations with or without urinary tract defects, SPAST-related motor disorder, hereditary neuromuscular disease, SERAC1-related neurological disorder, PRRT2-associated paroxysmal movement disorder, hereditary generalized epilepsy, VPS11-related neurological disorder, KIF5A-related neurological disorder, ATP1A3-associated neurological disorder, myopathy caused by variation in POMGNT1, SLC6A3-related dopamine transporter deficiency syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, dyskinesia with orofacial involvement, autosomal dominant, PAX6-related ocular dysgenesis, neuroocular syndrome, epilepsy, X-linked, with or without impaired intellectual development and dysmorphic features, encephalopathy, acute transient, LSM7-related leukodystrophy and cerebellar atrophy, infection-induced acute-onset axonal neuropathy, Valence-Farazi cerebellar ataxia syndrome, DHDDS-related syndrome

Subtypes (276): microcephaly and chorioretinopathy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, autosomal dominant primary microcephaly, Prader-Willi syndrome, Smith-Magenis syndrome, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, microcephalic osteodysplastic primordial dwarfism, type 3, CK syndrome, orofaciodigital syndrome I, Rett syndrome, Wieacker-Wolff syndrome, Amish lethal microcephaly, cerebral palsy, spastic quadriplegic, 2, Pitt-Hopkins-like syndrome 2, developmental delay with autism spectrum disorder and gait instability, complex cortical dysplasia with other brain malformations 5, AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome, intellectual disability, autosomal dominant 29, Au-Kline syndrome, cerebellar atrophy, visual impairment, and psychomotor retardation;, neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, cerebral palsy, spastic quadriplegic, 3, Okur-Chung neurodevelopmental syndrome, Harel-Yoon syndrome, neurodevelopmental disorder with hypotonia, seizures, and absent language, alternating hemiplegia of childhood, autosomal recessive primary microcephaly, Rubinstein-Taybi syndrome, neurodevelopmental disorder with cerebellar atrophy and with or without seizures, neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, neurodevelopmental disorder with hypotonia, microcephaly, and seizures, neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, neurodevelopmental disorder with language impairment and behavioral abnormalities, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities, neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities, neurodevelopmental disorder with or without early-onset generalized epilepsy, neurodevelopmental disorder with or without autism or seizures, neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism, neurodevelopmental disorder with dysmorphic facies and variable seizures, squalene synthase deficiency, intellectual developmental disorder and retinitis pigmentosa; IDDRP, neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, Houge-Janssens syndrome 3, neurodevelopmental disorder with central and peripheral motor dysfunction, neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, neurodevelopmental disorder with impaired speech and hyperkinetic movements, developmental delay with variable intellectual impairment and behavioral abnormalities, neurodevelopmental disorder with or without variable brain abnormalities; NEDBA, neurodevelopmental disorder with seizures and speech and walking impairment, neurodevelopmental disorder with microcephaly and structural brain anomalies, neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, neurodevelopmental disorder with visual defects and brain anomalies, neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, neurodevelopmental disorder with cerebellar hypoplasia and spasticity, neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies, neurodevelopmental disorder with absent language and variable seizures, neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures, neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, Poirier-Bienvenu neurodevelopmental syndrome, neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements, neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation, neurodevelopmental disorder with microcephaly and dysmorphic facies, neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies, neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia, neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, neurodevelopmental disorder with speech impairment and dysmorphic facies, neurodevelopmental disorder with alopecia and brain abnormalities, neurodevelopmental disorder with seizures and brain atrophy, neurodevelopmental disorder with microcephaly, seizures, and brain atrophy, Delpire-McNeill syndrome, neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination, developmental delay and seizures with or without movement abnormalities, Stankiewicz-Isidor syndrome, neurodevelopmental disorder with midbrain and hindbrain malformations, neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies, neurodevelopmental disorder with involuntary movements, neurodevelopmental disorder with hypotonia, neuropathy, and deafness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, neurodevelopmental disorder with microcephaly, ataxia, and seizures, neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy, neurodevelopmental disorder with severe motor impairment and absent language, neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, neurodevelopmental disorder with or without seizures and gait abnormalities, neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, neurodevelopmental disorder with poor language and loss of hand skills, neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, neurodevelopmental disorder with spasticity and poor growth, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, FOXG1 disorder, genetic developmental and epileptic encephalopathy, X-linked complex neurodevelopmental disorder, PPP2R1A-related intellectual disability, intellectual disability, autosomal dominant, CACNA1A-related complex neurodevelopmental disorder, X-linked intellectual disability, PAX5-related B lymphopenia and autism spectrum disorder, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, KCNH1 associated disorder, AFG2B-related complex neurodevelopmental disorder with motor features and hearing loss, intellectual disability, autosomal recessive, FAT4-related neurodevelopmental disorder, SOX11-related complex neurodevelopmental disorder with or without congenital anomalies, microcephaly with lissencephaly and/or hydranencephaly, MYH10-related neurodevelopmental disorder with congenital anomalies, CNOT9-related developmental disorder with seizures, HMGB1-related brachyphalangy, polydactyly and tibial aplasia syndrome, ATXN7L3-related developmental delay, hypotonia and facial dysmorphism, DIP2C-related developmental disorder with speech delay, EPB41L3-related developmental disorder with delayed myelination and seizures, GABRA4-related neurodevelopmental disorder with seizures, GABRD-related neurodevelopmental disorder with epilepsy, KCNK3-related developmental delay with sleep apnea, RFX3-related neurodevelopmental disorder with autism and other behavioural abnormalities, RFX4-related neurodevelopmental disorder with autism and other behavioural abnormalities, KDM2B-related neurodevelopmental disorder, TRA2B-related neurodevelopmental disorder, WDR5-related neurodevelopmental disorder, ARF3-related neurodevelopmental disorder, CBX1-related neurodevelopmental disorder, DDX17-related neurodevelopmental disorder, FEZF2-related neurodevelopmental disorder, HDAC3-related neurodevelopmental disorder, DEAF1-associated neurodevelopmental disorder, SYNCRIP-related neurodevelopmental disorder, HNRNPC-related neurodevelopmental disorder, NACC1-related neurodevelopmental disorder with epilepsy, cataracts and episodic irritability, SETD2-related neurodevelopmental disorder without or with macrocephaly/overgrowth, neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked, Alzahrani-Kuwahara syndrome, neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, Hiatt-Neu-Cooper neurodevelopmental syndrome, neurodevelopmental disorder with seizures and gingival overgrowth, neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, neurodevelopmental disorder with infantile epileptic spasms, neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, neurodevelopmental disorder with motor and speech delay and behavioral abnormalities, neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, neurodevelopmental disorder with hypotonia and dysmorphic facies, neurodevelopmental disorder with hypotonia and brain abnormalities, neurodevelopmental disorder with impaired language and ataxia and with or without seizures, neurodevelopmental disorder with hearing loss and spasticity, neurodevelopmental disorder with hypotonia and gross motor and speech delay, neurodevelopmental disorder with hyperkinetic movements and dyskinesia, neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, Marbach-Schaaf neurodevelopmental syndrome, neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis, Brunet-Wagner neurodevelopmental syndrome, Ferguson-Bonni neurodevelopmental syndrome, neurodevelopmental disorder with or without variable movement or behavioral abnormalities, neurodevelopmental disorder with central hypotonia and dysmorphic facies, neurodevelopmental disorder with neuromuscular and skeletal abnormalities, Chilton-Okur-Chung neurodevelopmental syndrome, neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities, parenti-mignot neurodevelopmental syndrome, neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures, Dentici-Novelli neurodevelopmental syndrome, neurodevelopmental disorder with poor growth and skeletal anomalies, neurodevelopmental disorder with language delay and seizures, neurodevelopmental disorder with dystonia and seizures, Dworschak-Punetha neurodevelopmental syndrome, neurodevelopmental disorder with epilepsy and brain atrophy, neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, neurodevelopmental disorder with speech delay and variable ocular anomalies, neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, neurodevelopmental disorder with spasticity, seizures, and brain abnormalities, neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, neurodevelopmental disorder with microcephaly, short stature, and speech delay, neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures, neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly, neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, neurodevelopmental disorder with eye movement abnormalities and ataxia, neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, neurodevelopmental disorder with speech impairment and with or without seizures, neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia, neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, neurodevelopmental disorder with poor growth and behavioral abnormalities, neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, neurodevelopmental disorder with absent speech and movement and behavioral abnormalities, neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, neurodevelopmental disorder with microcephaly and movement abnormalities, neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, neurodevelopmental disorder with language delay and variable cognitive abnormalities, neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, Hao-Fountain syndrome due to USP7 mutation, neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, neurodevelopmental disorder with hyperkinetic movements, seizures, and structural brain abnormalities, neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, Jeffries-Lakhani neurodevelopmental syndrome, neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder, neurodevelopmental disorder plus optic atrophy, neurodevelopmental disorder with progressive movement abnormalities, aplasia cutis-enamel dysplasia syndrome, neurodevelopmental disorder with hypotonia and seizures, El Hayek-Chahrour neurodevelopmental disorder, neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, otofacial neurodevelopmental syndrome, neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, Kariminejad neurodevelopmental syndrome, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, intellectual developmental disorder with polymicrogyria and seizures, neurodevelopmental disorder with speech or visual impairment and brain hypomyelination, neurodevelopmental disorder with microcephaly, absent speech, and hypotonia, neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia, neurodevelopmental disorder with progressive spasticity and brain abnormalities, neurodevelopmental disorder with thin corpus callosum, hypotonia, and absent language, neurodevelopmental disorder with white matter abnormalities and gait disturbance, neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalities, neurodevelopmental disorder with ataxia and brain abnormalities, neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, Li-Takada-Miyake syndrome, neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities, Nil-Deshwar neurodevelopmental syndrome, Popov-Chang syndrome, neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima, Dursun-Ozgul neurodevelopmental syndrome, neurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speech, neurodevelopmental disorder with speech delay and behavioral abnormalities, Harel-Tora neurodevelopmental syndrome, neurocardiorenal malformation syndrome, neurodevelopmental disorder with behavioral abnormalities and childhood-onset spastic paraplegia, neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, Ramond-Elliott neurodevelopmental syndrome, microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter, neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities, neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, PIP5K1C-related neurodevelopmental disorder, KCND2-related neurodevelopmental disorder with or without seizures, PRPF19-related neurodevelopmental disorder, CTR9-related neurodevelopmental disorder, CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy, PPFIA3-related neurodevelopmental disorder, dyneinopathy, MYCBP2-related developmental delay with corpus callosum defects, GRIN-related complex neurodevelopmental disorder, RNU5B-1 related neurodevelopmental disorder with seizures and joint laxity, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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.

Gene	Classification	Inheritance	Disease	Records
ATXN7L3	Strong	Autosomal dominant	complex neurodevelopmental disorder	2
FAM177A1	Strong	Autosomal recessive	Mendelian neurodevelopmental disorder	3
PRMT9	Moderate	Autosomal recessive	complex neurodevelopmental disorder	3

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FAM177A1	HGNC:19829	ENSG00000151327	Q8N128	Protein FAM177A1	gencc
PRMT9	HGNC:25099	ENSG00000164169	Q6P2P2	Protein arginine N-methyltransferase 9	gencc
ATXN7L3	HGNC:25416	ENSG00000087152	Q14CW9	Ataxin-7-like protein 3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRMT9	Protein arginine N-methyltransferase 9	Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA).
ATXN7L3	Ataxin-7-like protein 3	Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FAM177A1	Other/Unknown	no		FAM177
PRMT9	Enzyme (other)	yes	2.1.1.320	TPR-like_helical_dom_sf, TPR_rpt, Arg_MeTrfase
ATXN7L3	Other/Unknown	no		SCA7_dom, SAGA_su_Sgf11, SGF11

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
left testis	1
left ventricle myocardium	1
left ovary	1
primordial germ cell in gonad	1
secondary oocyte	1
cortical plate	1
prefrontal cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FAM177A1	258	ubiquitous	marker	calcaneal tendon, left ventricle myocardium, left testis
PRMT9	243	ubiquitous	marker	secondary oocyte, primordial germ cell in gonad, left ovary
ATXN7L3	249	ubiquitous	marker	prefrontal cortex, cortical plate, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRMT9	1,952
ATXN7L3	1,584
FAM177A1	544

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRMT9	Q6P2P2	4
ATXN7L3	Q14CW9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM177A1	Q8N128	64.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 3 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chromatin organization	1	81.6×	0.014	ATXN7L3
HATs acetylate histones	1	79.3×	0.014	ATXN7L3
Chromatin modifying enzymes	1	72.3×	0.014	ATXN7L3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of DNA repair	1	138.1×	0.035	ATXN7L3
regulation of RNA splicing	1	109.4×	0.035	ATXN7L3
methylation	1	85.1×	0.035	PRMT9
chromatin organization	1	49.6×	0.041	ATXN7L3
mRNA processing	1	39.4×	0.041	PRMT9
chromatin remodeling	1	36.5×	0.041	PRMT9
regulation of DNA-templated transcription	1	15.8×	0.079	PRMT9
positive regulation of DNA-templated transcription	1	14.0×	0.079	ATXN7L3
regulation of transcription by RNA polymerase II	1	5.8×	0.164	ATXN7L3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FAM177A1	0	0
PRMT9	0	0
ATXN7L3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRMT9	40	Binding:40

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRMT9	2.1.1.320	type II protein arginine methyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PRMT9
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	FAM177A1, ATXN7L3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FAM177A1	0	—
PRMT9	40	—
ATXN7L3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.