syndromic X-linked intellectual disability 5

Summary

syndromic X-linked intellectual disability 5 (MONDO:0010574) is a disease caused by AP1S2 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: AP1S2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 20
• Phenotypes (HPO): 7
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0000023	Inguinal hernia	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000256	Macrocephaly	Very frequent (80-99%)
HP:0000486	Strabismus	Very frequent (80-99%)
HP:0002119	Ventriculomegaly	Very frequent (80-99%)
HP:0002120	Cerebral cortical atrophy	Very frequent (80-99%)
HP:0007360	Aplasia/Hypoplasia of the cerebellum	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	syndromic X-linked intellectual disability 5
Mondo ID	MONDO:0010574
OMIM	304340
Orphanet	1568, 85329
DOID	DOID:0060800
NCIT	C124839
SNOMED CT	719139003
UMLS	C0796254
MedGen	162924
GARD	0008520
Is cancer (heuristic)	no

Also known as: Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures · intellectual disability X-linked syndromic 5 · intellectual disability X-linked with Dandy-Walker malformation basal ganglia disease and seizures · intellectual disability, X-linked syndromic 5 · mental retardation X-linked syndromic 5 · mental retardation X-linked with Dandy-Walker malformation basal ganglia disease and seizures · mental retardation, X-linked 59 · mental retardation, X-linked, syndromic 21 · mental retardation, X-linked, syndromic 5 · mental retardation, X-linked, syndromic, fried type · mental retardation, X-linked, with Dandy-Walker malformation, basal ganglia disease, and seizures · MRX59 · MRXS21 · MRXS5 · PETTIGREW syndrome · Pettigrew syndrome · Pettigrew syndrome, X-linked recessive · PGS · syndromic X-linked intellectual disability 21 · syndromic X-linked intellectual disability fried type (+6 more)

Data availability: 20 ClinVar variants · 6 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › syndromic X-linked intellectual disability 5

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, 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

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

20 retrieved; paginated sample, class counts are floors:

12 pathogenic, 5 likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10777	NM_001272071.2(AP1S2):c.106C>T (p.Gln36Ter)	AP1S2	Pathogenic	no assertion criteria provided
10778	NM_001272071.2(AP1S2):c.154C>T (p.Arg52Ter)	AP1S2	Pathogenic	criteria provided, multiple submitters, no conflicts
10779	NM_001272071.2(AP1S2):c.180-5_180-2del	AP1S2	Pathogenic	no assertion criteria provided
10781	NM_001272071.2(AP1S2):c.226G>T (p.Glu76Ter)	AP1S2	Pathogenic	no assertion criteria provided
140457	NM_001272071.2(AP1S2):c.426+1G>T	AP1S2	Pathogenic	criteria provided, single submitter
2442357	NM_001272071.2(AP1S2):c.288+1G>A	AP1S2	Pathogenic	criteria provided, single submitter
2446573	NM_001272071.2(AP1S2):c.367C>T (p.Gln123Ter)	AP1S2	Pathogenic	criteria provided, multiple submitters, no conflicts
3251646	NM_001272071.2(AP1S2):c.319del (p.Glu107fs)	AP1S2	Pathogenic	criteria provided, single submitter
397541	NM_001272071.2(AP1S2):c.1-3C>A	AP1S2	Pathogenic	criteria provided, single submitter
434219	NM_001272071.2(AP1S2):c.281del (p.Phe94fs)	AP1S2	Pathogenic	criteria provided, single submitter
504198	NM_001272071.2(AP1S2):c.40C>T (p.Arg14Ter)	AP1S2	Pathogenic	criteria provided, single submitter
929434	NM_001272071.2(AP1S2):c.-1+1G>A	AP1S2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988587	NM_001272071.2(AP1S2):c.1-2A>G	AP1S2	Pathogenic	no assertion criteria provided
10780	NM_001272071.2(AP1S2):c.288+5G>A	AP1S2	Likely pathogenic	criteria provided, single submitter
2444373	NM_001272071.2(AP1S2):c.21del (p.Phe7fs)	AP1S2	Likely pathogenic	criteria provided, single submitter
3898008	NM_001272071.2(AP1S2):c.357del (p.Glu121fs)	AP1S2	Likely pathogenic	criteria provided, single submitter
4293012	NM_001272071.2(AP1S2):c.65del (p.Leu22fs)	AP1S2	Likely pathogenic	criteria provided, single submitter
972700	NM_001272071.2(AP1S2):c.321_334del (p.Glu107fs)	AP1S2	Likely pathogenic	criteria provided, single submitter
434871	NM_001079872.2(CUL4B):c.2633G>A (p.Arg878Gln)	CUL4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2500867	NM_001272071.2(AP1S2):c.*241A>C	AP1S2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · 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
AP1S2	Definitive	X-linked	syndromic X-linked intellectual disability 5	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AP1S2	Orphanet:1568	X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome
AP1S2	Orphanet:85329	X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome
AP1S2	Orphanet:85335	Fried syndrome
CUL4B	Orphanet:85293	X-linked intellectual disability, Cabezas type

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AP1S2	HGNC:560	ENSG00000182287	P56377	AP-1 complex subunit sigma-2	gencc,clinvar
CUL4B	HGNC:2555	ENSG00000158290	Q13620	Cullin-4B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AP1S2	AP-1 complex subunit sigma-2	Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes.
CUL4B	Cullin-4B	Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AP1S2	Other/Unknown	no		Clathrin_sm-chain_CS, Longin-like_dom_sf, AP_complex_ssu
CUL4B	Other/Unknown	no		Cullin_N, Cullin_CS, Cullin_homology

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	2
cauda epididymis	1
monocyte	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AP1S2	289	ubiquitous	marker	corpus epididymis, cauda epididymis, monocyte
CUL4B	291	ubiquitous	marker	sperm, male germ cell, corpus epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CUL4B	4,342
AP1S2	1,346

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CUL4B	Q13620	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AP1S2	P56377	94.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nef mediated downregulation of MHC class I complex cell surface expression	1	571.0×	0.018	AP1S2
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	317.2×	0.018	AP1S2
The role of Nef in HIV-1 replication and disease pathogenesis	1	317.2×	0.018	AP1S2
Recognition of DNA damage by PCNA-containing replication complex	1	190.3×	0.018	CUL4B
Host Interactions of HIV factors	1	167.9×	0.018	AP1S2
Lysosome Vesicle Biogenesis	1	163.1×	0.018	AP1S2
DNA Damage Recognition in GG-NER	1	142.8×	0.018	CUL4B
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1	132.8×	0.018	CUL4B
Dual Incision in GG-NER	1	129.8×	0.018	CUL4B
trans-Golgi Network Vesicle Budding	1	126.9×	0.018	AP1S2
Formation of Incision Complex in GG-NER	1	126.9×	0.018	CUL4B
Formation of TC-NER Pre-Incision Complex	1	105.7×	0.019	CUL4B
Golgi Associated Vesicle Biogenesis	1	100.2×	0.019	AP1S2
Gap-filling DNA repair synthesis and ligation in TC-NER	1	89.2×	0.019	CUL4B
Dual incision in TC-NER	1	86.5×	0.019	CUL4B
HIV Infection	1	59.5×	0.026	AP1S2
MHC class II antigen presentation	1	44.6×	0.033	AP1S2
Neddylation	1	23.7×	0.058	CUL4B
Membrane Trafficking	1	18.5×	0.070	AP1S2
Vesicle-mediated transport	1	17.4×	0.071	AP1S2
Viral Infection Pathways	1	15.4×	0.075	AP1S2
Adaptive Immune System	1	14.9×	0.075	AP1S2
Infectious disease	1	12.4×	0.086	AP1S2
Disease	1	6.5×	0.148	AP1S2
Immune System	1	6.5×	0.148	AP1S2

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
UV-damage excision repair	1	648.1×	0.009	CUL4B
melanosome assembly	1	443.5×	0.009	AP1S2
proteasomal protein catabolic process	1	383.0×	0.009	CUL4B
astrocyte differentiation	1	383.0×	0.009	CUL4B
platelet dense granule organization	1	337.0×	0.009	AP1S2
ribosome biogenesis	1	312.1×	0.009	CUL4B
positive regulation of G1/S transition of mitotic cell cycle	1	200.6×	0.012	CUL4B
cellular response to UV	1	147.8×	0.014	CUL4B
positive regulation of protein catabolic process	1	101.5×	0.017	CUL4B
G1/S transition of mitotic cell cycle	1	100.3×	0.017	CUL4B
protein polyubiquitination	1	57.7×	0.027	CUL4B
vesicle-mediated transport	1	48.1×	0.029	AP1S2
gene expression	1	39.9×	0.032	CUL4B
ubiquitin-dependent protein catabolic process	1	37.1×	0.032	CUL4B
intracellular protein transport	1	32.4×	0.035	AP1S2
DNA damage response	1	26.8×	0.039	CUL4B
protein ubiquitination	1	20.7×	0.048	CUL4B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AP1S2	0	0
CUL4B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CUL4B	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	AP1S2, CUL4B

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)
AP1S2	0	—
CUL4B	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07546175	Not specified	NOT_YET_RECRUITING	Clinical Study of Electroacupuncture for Postoperative Gastroparesis in Patients With Digestive Tract Tumors