CTCF-related neurodevelopmental disorder

Summary

CTCF-related neurodevelopmental disorder (MONDO:0014213) is a disease caused by CTCF (GenCC Definitive), with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CTCF (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 99
• Phenotypes (HPO): 71

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

71 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000219	Thin upper lip vermilion	Frequent (30-79%)
HP:0000233	Thin vermilion border	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000527	Long eyelashes	Frequent (30-79%)
HP:0000540	Hypermetropia	Frequent (30-79%)
HP:0000574	Thick eyebrow	Frequent (30-79%)
HP:0000675	Macrodontia of permanent maxillary central incisor	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0000954	Single transverse palmar crease	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001518	Small for gestational age	Frequent (30-79%)
HP:0001631	Atrial septal defect	Frequent (30-79%)
HP:0001643	Patent ductus arteriosus	Frequent (30-79%)
HP:0001852	Sandal gap	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0010059	Broad hallux phalanx	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0012758	Neurodevelopmental delay	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000059	Hypoplastic labia majora	Occasional (5-29%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000322	Short philtrum	Occasional (5-29%)
HP:0000341	Narrow forehead	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000348	High forehead	Occasional (5-29%)
HP:0000358	Posteriorly rotated ears	Occasional (5-29%)
HP:0000378	Cupped ear	Occasional (5-29%)
HP:0000455	Broad nasal tip	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000482	Microcornea	Occasional (5-29%)
HP:0000490	Deeply set eye	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)
HP:0000691	Microdontia	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)
HP:0000960	Sacral dimple	Occasional (5-29%)
HP:0000998	Hypertrichosis	Occasional (5-29%)
HP:0001212	Prominent fingertip pads	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	CTCF-related neurodevelopmental disorder
Mondo ID	MONDO:0014213
OMIM	615502
Orphanet	363611
DOID	DOID:0070051
UMLS	C3809686
MedGen	816016
GARD	0017566
Is cancer (heuristic)	no

Also known as: intellectual development disorder, autosomal dominant 21 · intellectual disability, autosomal dominant 21 · intellectual disability, autosomal dominant type 21 · intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome · mental retardation, autosomal dominant 21 · mental retardation, autosomal dominant type 21 · MRD21

Data availability: 99 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › CTCF-related neurodevelopmental disorder

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, spina bifida, 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, 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

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

99 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 28 likely pathogenic, 21 pathogenic, 9 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 2 not provided, 2 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065488	NM_006565.4(CTCF):c.782-1G>C	CTCF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1203833	NM_006565.4(CTCF):c.1343G>A (p.Arg448Gln)	CTCF	Pathogenic	criteria provided, multiple submitters, no conflicts
1220439	NM_006565.4(CTCF):c.1025G>A (p.Arg342His)	CTCF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1254810	NM_006565.4(CTCF):c.677A>G (p.Tyr226Cys)	CTCF	Pathogenic	criteria provided, multiple submitters, no conflicts
1325769	NM_006565.4(CTCF):c.148dup (p.Val50fs)	CTCF	Pathogenic	criteria provided, single submitter
1325770	NM_006565.4(CTCF):c.688del (p.Glu230fs)	CTCF	Pathogenic	criteria provided, single submitter
1325772	NM_006565.4(CTCF):c.804_805del (p.Cys268_Glu269delinsTer)	CTCF	Pathogenic	criteria provided, single submitter
1325777	NM_006565.4(CTCF):c.1102C>T (p.Arg368Cys)	CTCF	Pathogenic	criteria provided, multiple submitters, no conflicts
1325778	NM_006565.4(CTCF):c.1103G>A (p.Arg368His)	CTCF	Pathogenic	criteria provided, multiple submitters, no conflicts
1325779	NM_006565.4(CTCF):c.1117C>G (p.His373Asp)	CTCF	Pathogenic	criteria provided, single submitter
1325781	NM_006565.4(CTCF):c.1133C>T (p.Pro378Leu)	CTCF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1325788	NM_006565.4(CTCF):c.292_293del (p.Leu98fs)	CTCF	Pathogenic	criteria provided, single submitter
1343232	NM_006565.4(CTCF):c.1223_1226del (p.Glu408fs)	CTCF	Pathogenic	no assertion criteria provided
3378409	NM_006565.4(CTCF):c.782-2A>T	CTCF	Pathogenic	criteria provided, single submitter
3571458	GRCh38/hg38 16q22.1(chr16:67623831-67627229)x1	CTCF	Pathogenic	criteria provided, single submitter
3900669	NM_006565.4(CTCF):c.1633del (p.Tyr545fs)	CTCF	Pathogenic	no assertion criteria provided
4081928	NM_006565.4(CTCF):c.633del (p.Lys211fs)	CTCF	Pathogenic	no assertion criteria provided
429261	NM_006565.4(CTCF):c.1024C>T (p.Arg342Cys)	CTCF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521287	NM_006565.4(CTCF):c.615_618del (p.Lys206fs)	CTCF	Pathogenic	criteria provided, multiple submitters, no conflicts
522045	NM_006565.4(CTCF):c.782-2A>G	CTCF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
625526	NM_006565.4(CTCF):c.773_776del (p.Lys258fs)	CTCF	Pathogenic	criteria provided, single submitter
803262	NM_006565.4(CTCF):c.1990C>T (p.Gln664Ter)	CTCF	Pathogenic	criteria provided, single submitter
88636	NM_006565.4(CTCF):c.375dup (p.Val126fs)	CTCF	Pathogenic	criteria provided, single submitter
88637	NM_006565.4(CTCF):c.1186dup (p.Arg396fs)	CTCF	Pathogenic	criteria provided, single submitter
88638	NM_006565.4(CTCF):c.1699C>T (p.Arg567Trp)	CTCF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
984936	NM_006565.4(CTCF):c.778_781del (p.Lys260fs)	CTCF	Pathogenic	criteria provided, multiple submitters, no conflicts
998024	NM_006565.4(CTCF):c.329dup (p.Gly111fs)	CTCF	Pathogenic	criteria provided, single submitter
1065421	NM_006565.4(CTCF):c.1119T>A (p.His373Gln)	CTCF	Likely pathogenic	criteria provided, single submitter
1325773	NM_006565.4(CTCF):c.1960C>T (p.Arg654Ter)	CTCF	Likely pathogenic	criteria provided, single submitter
1325774	NM_006565.4(CTCF):c.782-1G>T	CTCF	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CTCF	Definitive	Autosomal dominant	CTCF-related neurodevelopmental disorder	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTCF	Orphanet:363611	CTCF-related neurodevelopmental disorder
GRIN2A	Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome
GRIN2A	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
GRIN2A	Orphanet:289266	Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation
GRIN2A	Orphanet:725	Developmental and epileptic encephalopathy with spike-wave activation in sleep
GRIN2A	Orphanet:98818	Landau-Kleffner syndrome
KIF11	Orphanet:2526	Microcephaly-lymphedema-chorioretinopathy syndrome
MPDZ	Orphanet:269505	Congenital communicating hydrocephalus

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTCF	HGNC:13723	ENSG00000102974	P49711	Transcriptional repressor CTCF	gencc,clinvar
GRIN2A	HGNC:4585	ENSG00000183454	Q12879	Glutamate receptor ionotropic, NMDA 2A	clinvar
KIF11	HGNC:6388	ENSG00000138160	P52732	Kinesin-like protein KIF11	clinvar
MPDZ	HGNC:7208	ENSG00000107186	O75970	Multiple PDZ domain protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTCF	Transcriptional repressor CTCF	Chromatin binding factor that binds to DNA sequence specific sites and regulates the 3D structure of chromatin.
GRIN2A	Glutamate receptor ionotropic, NMDA 2A	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
KIF11	Kinesin-like protein KIF11	Motor protein required for establishing a bipolar spindle and thus contributing to chromosome congression during mitosis.
MPDZ	Multiple PDZ domain protein	Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.25

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
Scaffold/PPI	1	4.3×	0.538
Enzyme (other)	1	3.0×	0.538
Transcription factor	1	2.1×	0.538
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTCF	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger_PRDM4/PRDM1/PRDM14
GRIN2A	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
KIF11	Enzyme (other)	yes	5.6.1.3	Kinesin_motor_dom, Kinesin_motor_CS, Kinesin-assoc_MT-bd_dom
MPDZ	Scaffold/PPI	no		PDZ, L27_dom, L27_2

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	3
ganglionic eminence	2
endometrium epithelium	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1
embryo	1
calcaneal tendon	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTCF	297	ubiquitous	marker	ventricular zone, ganglionic eminence, endometrium epithelium
GRIN2A	199	broad	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus
KIF11	205	ubiquitous	marker	ventricular zone, ganglionic eminence, embryo
MPDZ	274	ubiquitous	marker	calcaneal tendon, corpus callosum, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTCF	5,713
KIF11	3,788
MPDZ	3,527
GRIN2A	3,146

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF11	P52732	62
GRIN2A	Q12879	37
CTCF	P49711	21
MPDZ	O75970	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MECP2 regulates neuronal receptors and channels	1	200.3×	0.025	GRIN2A
Unblocking of NMDA receptors, glutamate binding and activation	1	181.3×	0.025	GRIN2A
Synaptic adhesion-like molecules	1	181.3×	0.025	GRIN2A
Negative regulation of NMDA receptor-mediated neuronal transmission	1	181.3×	0.025	GRIN2A
Long-term potentiation	1	158.6×	0.025	GRIN2A
Assembly and cell surface presentation of NMDA receptors	1	84.6×	0.039	GRIN2A
Neurexins and neuroligins	1	65.6×	0.042	GRIN2A
Kinesins	1	59.5×	0.042	KIF11
CHD6, CHD7, CHD8, CHD9 subfamily	1	49.4×	0.045	CTCF
Golgi-to-ER retrograde transport	1	44.3×	0.045	KIF11
COPI-dependent Golgi-to-ER retrograde traffic	1	37.0×	0.047	KIF11
Intra-Golgi and retrograde Golgi-to-ER traffic	1	34.9×	0.047	KIF11
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	30.4×	0.048	CTCF
MHC class II antigen presentation	1	29.7×	0.048	KIF11
Factors involved in megakaryocyte development and platelet production	1	22.1×	0.059	KIF11
Membrane Trafficking	1	12.4×	0.093	KIF11
Hemostasis	1	12.0×	0.093	KIF11
Vesicle-mediated transport	1	11.6×	0.093	KIF11
Adaptive Immune System	1	9.9×	0.102	KIF11
Immune System	1	4.3×	0.214	KIF11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
directional locomotion	1	1404.3×	0.011	GRIN2A
spindle elongation	1	1404.3×	0.011	KIF11
regulation of centromeric sister chromatid cohesion	1	1404.3×	0.011	CTCF
protein localization to postsynaptic membrane	1	1404.3×	0.011	GRIN2A
regulation of mitotic centrosome separation	1	842.6×	0.012	KIF11
mitotic centrosome separation	1	702.2×	0.012	KIF11
sleep	1	601.9×	0.012	GRIN2A
tight junction assembly	1	601.9×	0.012	MPDZ
protein localization to chromosome, centromeric region	1	526.6×	0.012	CTCF
regulation of monoatomic cation transmembrane transport	1	526.6×	0.012	GRIN2A
serotonin metabolic process	1	421.3×	0.013	GRIN2A
calcium ion transmembrane import into cytosol	1	383.0×	0.013	GRIN2A
ionotropic glutamate receptor signaling pathway	1	324.1×	0.013	GRIN2A
excitatory chemical synaptic transmission	1	324.1×	0.013	GRIN2A
chromatin looping	1	300.9×	0.013	CTCF
startle response	1	280.9×	0.013	GRIN2A
negative regulation of gene expression via chromosomal CpG island methylation	1	263.3×	0.013	CTCF
spindle organization	1	247.8×	0.013	KIF11
dopamine metabolic process	1	247.8×	0.013	GRIN2A
genomic imprinting	1	247.8×	0.013	CTCF
glutamate receptor signaling pathway	1	234.1×	0.013	GRIN2A
regulation of neuronal synaptic plasticity	1	168.5×	0.016	GRIN2A
positive regulation of synaptic transmission, glutamatergic	1	156.0×	0.016	GRIN2A
cardiac muscle cell development	1	156.0×	0.016	CTCF
monoatomic cation transmembrane transport	1	156.0×	0.016	GRIN2A
DNA methylation-dependent constitutive heterochromatin formation	1	135.9×	0.018	CTCF
positive regulation of excitatory postsynaptic potential	1	131.7×	0.018	GRIN2A
response to amphetamine	1	123.9×	0.018	GRIN2A
excitatory postsynaptic potential	1	110.9×	0.020	GRIN2A
epigenetic regulation of gene expression	1	95.8×	0.022	CTCF

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 3 of 4 evidence-associated genes (75%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GRIN2A	MEMANTINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRIN2A	37	4
KIF11	6	3
CTCF	0	0
MPDZ	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MEMANTINE HYDROCHLORIDE	4	GRIN2A
ESKETAMINE	4	GRIN2A
DEXTROMETHORPHAN	4	GRIN2A
PENTAMIDINE	4	GRIN2A
AMANTADINE	4	GRIN2A
KETAMINE	4	GRIN2A
CYCLOSERINE	4	GRIN2A
MEMANTINE	4	GRIN2A
TACRINE	4	GRIN2A
LEVORPHANOL	4	GRIN2A
CHLORPROMAZINE	4	GRIN2A
PROCYCLIDINE	4	GRIN2A
ORPHENADRINE	4	GRIN2A
ESMETHADONE	3	GRIN2A
DALZANEMDOR	3	GRIN2A
LATREPIRDINE	3	GRIN2A
GLUTAMIC ACID	3	GRIN2A
GOSSYPOL	3	KIF11
DEXOXADROL	2	GRIN2A
DEXTRORPHAN	2	GRIN2A
LEVOMETHADONE	2	GRIN2A
ALPHAMETHADOL	2	GRIN2A
BETAMETHADOL	2	GRIN2A
DIMEMORFAN	2	GRIN2A
PHENCYCLIDINE	2	GRIN2A
DIZOCILPINE	2	GRIN2A
ETOXADROL	2	GRIN2A
IFENPRODIL	2	GRIN2A
TEZAMPANEL ANHYDROUS	2	GRIN2A
TRAXOPRODIL	2	GRIN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GRIN2A	324	Binding:296, Functional:23, ADMET:4, Toxicity:1
KIF11	193	Binding:185, Functional:8
CTCF	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIF11	5.6.1.3	plus-end-directed kinesin ATPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GRIN2A	324
KIF11	193

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
MEMANTINE HYDROCHLORIDE	4	GRIN2A
ESKETAMINE	4	GRIN2A
DEXTROMETHORPHAN	4	GRIN2A
PENTAMIDINE	4	GRIN2A
AMANTADINE	4	GRIN2A
KETAMINE	4	GRIN2A
CYCLOSERINE	4	GRIN2A
MEMANTINE	4	GRIN2A
TACRINE	4	GRIN2A
LEVORPHANOL	4	GRIN2A
CHLORPROMAZINE	4	GRIN2A
PROCYCLIDINE	4	GRIN2A
ORPHENADRINE	4	GRIN2A
ESMETHADONE	3	GRIN2A
DALZANEMDOR	3	GRIN2A
LATREPIRDINE	3	GRIN2A
GLUTAMIC ACID	3	GRIN2A
GOSSYPOL	3	KIF11
DEXOXADROL	2	GRIN2A
DEXTRORPHAN	2	GRIN2A
LEVOMETHADONE	2	GRIN2A
ALPHAMETHADOL	2	GRIN2A
BETAMETHADOL	2	GRIN2A
DIMEMORFAN	2	GRIN2A
PHENCYCLIDINE	2	GRIN2A
DIZOCILPINE	2	GRIN2A
ETOXADROL	2	GRIN2A
IFENPRODIL	2	GRIN2A
TEZAMPANEL ANHYDROUS	2	GRIN2A
TRAXOPRODIL	2	GRIN2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRIN2A
B	Phased (≥1) drug, not yet approved	1	KIF11
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CTCF, MPDZ

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CTCF	2	—
MPDZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.