syndromic X-linked intellectual disability Claes-Jensen type

Summary

syndromic X-linked intellectual disability Claes-Jensen type (MONDO:0010355) is a disease caused by KDM5C (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: KDM5C (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 180
• Phenotypes (HPO): 25

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)

25 HPO clinical features (Orphanet curated; top 25 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000327	Hypoplasia of the maxilla	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0002232	Patchy alopecia	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0000718	Aggressive behavior	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000411	Protruding ear	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000490	Deeply set eye	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0001182	Tapered finger	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0004279	Short palm	Occasional (5-29%)
HP:0007565	Multiple cafe-au-lait spots	Occasional (5-29%)
HP:0008734	Decreased testicular size	Occasional (5-29%)
HP:0030084	Clinodactyly	Occasional (5-29%)
HP:0100490	Camptodactyly of finger	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	syndromic X-linked intellectual disability Claes-Jensen type
Mondo ID	MONDO:0010355
MeSH	C564494
OMIM	300534
Orphanet	85279
DOID	DOID:0060809
SNOMED CT	719161008
UMLS	C1845243
MedGen	335139
GARD	0016744
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, X-linked recessive · intellectual disability, X-linked, syndromic, Claes-Jensen type · mental retardation, X-linked, syndromic, Claes-Jensen type · mental retardation, X-linked, syndromic, JARID1C-related · MRXSCJ · MRXSJ · syndromic X-linked intellectual disability Claes-Jensen type · syndromic X-linked intellectual disability JARID1C-related

Data availability: 180 ClinVar variants · 5 GenCC gene-disease records.

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 Claes-Jensen type

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, 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

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

180 retrieved; paginated sample, class counts are floors:

66 uncertain significance, 51 likely pathogenic, 42 pathogenic, 8 conflicting classifications of pathogenicity, 5 pathogenic/likely pathogenic, 5 benign/likely benign, 2 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
208547	NM_001356.5(DDX3X):c.977G>A (p.Arg326His)	DDX3X	Pathogenic	criteria provided, multiple submitters, no conflicts
1034062	NM_004187.5(KDM5C):c.3244dup (p.Arg1082fs)	KDM5C	Pathogenic	criteria provided, single submitter
1174937	NM_004187.5(KDM5C):c.80C>T (p.Pro27Leu)	KDM5C	Pathogenic	criteria provided, single submitter
1209852	NM_004187.5(KDM5C):c.2116C>T (p.Gln706Ter)	KDM5C	Pathogenic	criteria provided, single submitter
1319929	NM_004187.5(KDM5C):c.1361_1362del (p.Pro454fs)	KDM5C	Pathogenic	no assertion criteria provided
1334775	NM_004187.5(KDM5C):c.2517_2622del	KDM5C	Pathogenic	no assertion criteria provided
1455486	NM_004187.5(KDM5C):c.2908C>T (p.Gln970Ter)	KDM5C	Pathogenic	criteria provided, multiple submitters, no conflicts
1679365	NM_004187.5(KDM5C):c.12dup (p.Ser5fs)	KDM5C	Pathogenic	criteria provided, single submitter
1684146	NM_004187.5(KDM5C):c.2427_2430del (p.Glu810fs)	KDM5C	Pathogenic	criteria provided, multiple submitters, no conflicts
1685904	NM_004187.5(KDM5C):c.997G>C (p.Gly333Arg)	KDM5C	Pathogenic	criteria provided, single submitter
1685906	NM_004187.5(KDM5C):c.994C>T (p.Arg332Ter)	KDM5C	Pathogenic	criteria provided, multiple submitters, no conflicts
1687694	NM_004187.5(KDM5C):c.1510G>A (p.Val504Met)	KDM5C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803987	NM_004187.5(KDM5C):c.2214C>A (p.Cys738Ter)	KDM5C	Pathogenic	criteria provided, single submitter
1805730	NM_004187.5(KDM5C):c.2813_2816dup (p.Pro940fs)	KDM5C	Pathogenic	criteria provided, single submitter
211249	NM_004187.5(KDM5C):c.3118C>T (p.Gln1040Ter)	KDM5C	Pathogenic	criteria provided, single submitter
2430130	NM_004187.5(KDM5C):c.2993del (p.Pro998fs)	KDM5C	Pathogenic	criteria provided, single submitter
2442352	NM_004187.5(KDM5C):c.1616C>G (p.Ser539Ter)	KDM5C	Pathogenic	criteria provided, single submitter
254174	NM_004187.5(KDM5C):c.156G>T (p.Trp52Cys)	KDM5C	Pathogenic	no assertion criteria provided
2579750	NM_004187.5(KDM5C):c.2704C>T (p.Gln902Ter)	KDM5C	Pathogenic	criteria provided, single submitter
2580905	NM_004187.5(KDM5C):c.3624G>A (p.Trp1208Ter)	KDM5C	Pathogenic	criteria provided, single submitter
2756787	NM_004187.5(KDM5C):c.974_975del (p.Tyr325fs)	KDM5C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29996	NM_004187.5(KDM5C):c.2172C>A (p.Cys724Ter)	KDM5C	Pathogenic	no assertion criteria provided
3075726	NM_004187.5(KDM5C):c.3749C>G (p.Ser1250Ter)	KDM5C	Pathogenic	criteria provided, single submitter
3237467	NM_004187.5(KDM5C):c.1866G>A (p.Trp622Ter)	KDM5C	Pathogenic	criteria provided, single submitter
3377327	NM_004187.5(KDM5C):c.1592C>T (p.Pro531Leu)	KDM5C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374324	NM_004187.5(KDM5C):c.1439C>T (p.Pro480Leu)	KDM5C	Pathogenic	criteria provided, multiple submitters, no conflicts
375584	NM_004187.5(KDM5C):c.2622+2dup	KDM5C	Pathogenic	no assertion criteria provided
3774478	G384D	KDM5C	Pathogenic	no assertion criteria provided
397527	NM_004187.5(KDM5C):c.769_770del (p.Leu257fs)	KDM5C	Pathogenic	criteria provided, single submitter
4056406	NM_004187.5(KDM5C):c.3559_3562del (p.Ile1187fs)	KDM5C	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · 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
KDM5C	Definitive	X-linked	syndromic X-linked intellectual disability Claes-Jensen type	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KDM5C	Orphanet:85279	KDM5C-related syndromic X-linked intellectual disability
DDX3X	Orphanet:3338	Toriello-Carey syndrome
DDX3X	Orphanet:457260	X-linked intellectual disability-hypotonia-movement disorder syndrome
DDX3X	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
FGD1	Orphanet:915	Aarskog-Scott syndrome

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
KDM5C	HGNC:11114	ENSG00000126012	P41229	Lysine-specific demethylase 5C	gencc,clinvar
DDX3X	HGNC:2745	ENSG00000215301	O00571	ATP-dependent RNA helicase DDX3X	clinvar
FGD1	HGNC:3663	ENSG00000102302	P98174	FYVE, RhoGEF and PH domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KDM5C	Lysine-specific demethylase 5C	Histone demethylase that specifically demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code.
DDX3X	ATP-dependent RNA helicase DDX3X	Multifunctional ATP-dependent RNA helicase.
FGD1	FYVE, RhoGEF and PH domain-containing protein 1	Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 0 · 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
Transcription factor	2	5.5×	0.081
Enzyme (other)	1	4.0×	0.230

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KDM5C	Transcription factor	no	1.14.11.67	ARID_dom, Znf_PHD, JmjC_dom
DDX3X	Enzyme (other)	yes	3.6.4.13	RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
FGD1	Transcription factor	no		DH_dom, Znf_FYVE, PH_domain

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
right uterine tube	1
sural nerve	1
choroid plexus epithelium	1
oocyte	1
sperm	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KDM5C	279	ubiquitous	marker	sural nerve, stromal cell of endometrium, right uterine tube
DDX3X	294	ubiquitous	marker	choroid plexus epithelium, oocyte, sperm
FGD1	179	ubiquitous	yes	cortical plate, stromal cell of endometrium, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDX3X	6,454
KDM5C	4,183
FGD1	932

Intra-cohort edges

A	B	Sources
DDX3X	KDM5C	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DDX3X	O00571	17
KDM5C	P41229	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FGD1	P98174	66.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 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
Dengue virus activates/modulates innate and adaptive immune responses	1	112.0×	0.043	DDX3X
HDMs demethylate histones	1	76.1×	0.043	KDM5C
NRAGE signals death through JNK	1	61.4×	0.043	FGD1
G alpha (12/13) signalling events	1	45.9×	0.043	FGD1
Chromatin organization	1	27.2×	0.047	KDM5C
Chromatin modifying enzymes	1	24.1×	0.047	KDM5C
CDC42 GTPase cycle	1	24.1×	0.047	FGD1
Neutrophil degranulation	1	7.7×	0.124	DDX3X

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of toll-like receptor 8 signaling pathway	1	1872.4×	0.010	DDX3X
positive regulation of translation in response to endoplasmic reticulum stress	1	1404.3×	0.010	DDX3X
positive regulation of toll-like receptor 7 signaling pathway	1	1123.5×	0.010	DDX3X
positive regulation of chemokine (C-C motif) ligand 5 production	1	936.2×	0.010	DDX3X
cytosolic ribosome assembly	1	802.5×	0.010	DDX3X
cellular response to arsenic-containing substance	1	702.2×	0.010	DDX3X
positive regulation of protein K63-linked ubiquitination	1	702.2×	0.010	DDX3X
protein localization to cytoplasmic stress granule	1	702.2×	0.010	DDX3X
cellular response to osmotic stress	1	401.2×	0.015	DDX3X
positive regulation of mitochondrial translation	1	374.5×	0.015	DDX3X
cytoplasmic pattern recognition receptor signaling pathway	1	295.6×	0.015	DDX3X
gamete generation	1	295.6×	0.015	DDX3X
positive regulation of translational initiation	1	280.9×	0.015	DDX3X
negative regulation of intrinsic apoptotic signaling pathway	1	255.3×	0.015	DDX3X
positive regulation of interferon-alpha production	1	216.1×	0.015	DDX3X
filopodium assembly	1	216.1×	0.015	FGD1
stress granule assembly	1	200.6×	0.015	DDX3X
positive regulation of viral genome replication	1	193.7×	0.015	DDX3X
positive regulation of NLRP3 inflammasome complex assembly	1	193.7×	0.015	DDX3X
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	193.7×	0.015	DDX3X
regulation of GTPase activity	1	170.2×	0.015	FGD1
negative regulation of non-canonical NF-kappaB signal transduction	1	170.2×	0.015	DDX3X
negative regulation of protein-containing complex assembly	1	151.8×	0.016	DDX3X
positive regulation of type I interferon production	1	140.4×	0.016	DDX3X
extrinsic apoptotic signaling pathway via death domain receptors	1	133.8×	0.016	DDX3X
positive regulation of G1/S transition of mitotic cell cycle	1	133.8×	0.016	DDX3X
positive regulation of interferon-beta production	1	130.6×	0.016	DDX3X
translational initiation	1	119.5×	0.017	DDX3X
intrinsic apoptotic signaling pathway	1	119.5×	0.017	DDX3X
lipid homeostasis	1	112.3×	0.017	DDX3X

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 evidence-associated genes (100%) 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
KDM5C	DEFERIPRONE
DDX3X	IMATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KDM5C	1	4
DDX3X	1	4
FGD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DEFERIPRONE	4	KDM5C
IMATINIB	4	DDX3X

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
KDM5C	49	Binding:49
DDX3X	32	Binding:31, ADMET:1
FGD1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KDM5C	1.14.11.67	[histone H3]-trimethyl-L-lysine4 demethylase
DDX3X	3.6.4.13	RNA helicase

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

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

Compound	Max phase	Cohort target (bioactivity)
DEFERIPRONE	4	KDM5C
IMATINIB	4	DDX3X

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	KDM5C, DDX3X
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	1	FGD1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FGD1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.