Congenital cataracts-facial dysmorphism-neuropathy syndrome

Summary

Congenital cataracts-facial dysmorphism-neuropathy syndrome (MONDO:0011402) is a disease caused by CTDP1 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CTDP1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 22
• Phenotypes (HPO): 32
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		170	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0000518	Cataract	Very frequent (80-99%)
HP:0000568	Microphthalmia	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0000763	Sensory neuropathy	Very frequent (80-99%)
HP:0001256	Intellectual disability, mild	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0002808	Kyphosis	Very frequent (80-99%)
HP:0003134	Abnormality of peripheral nerve conduction	Very frequent (80-99%)
HP:0003401	Paresthesia	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005830	Flexion contracture of toe	Very frequent (80-99%)
HP:0007182	Peripheral hypomyelination	Very frequent (80-99%)
HP:0010620	Malar prominence	Very frequent (80-99%)
HP:0034681	Finger joint contracture	Very frequent (80-99%)
HP:0000044	Hypogonadotropic hypogonadism	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000482	Microcornea	Very frequent (80-99%)
HP:0000486	Strabismus	Very frequent (80-99%)
HP:0000939	Osteoporosis	Frequent (30-79%)
HP:0002120	Cerebral cortical atrophy	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0030890	Hyperintensity of cerebral white matter on MRI	Frequent (30-79%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001310	Dysmetria	Occasional (5-29%)
HP:0001943	Hypoglycemia	Occasional (5-29%)
HP:0002072	Chorea	Occasional (5-29%)
HP:0002080	Intention tremor	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0003319	Abnormality of the cervical spine	Occasional (5-29%)
HP:0007256	Abnormal pyramidal sign	Occasional (5-29%)
HP:0008942	Acute rhabdomyolysis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital cataracts-facial dysmorphism-neuropathy syndrome
Mondo ID	MONDO:0011402
MeSH	C565822
OMIM	604168
Orphanet	48431
SNOMED CT	702433001
UMLS	C1858726
MedGen	346973
GARD	0016645
Is cancer (heuristic)	no

Also known as: CCFDN · congenital cataracts, facial dysmorphism, and neuropathy · congenital cataracts-facial dysmorphism-neuropathy syndrome

Data availability: 22 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 › congenital cataracts-facial dysmorphism-neuropathy syndrome

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, 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

22 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 6 benign, 3 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 pathogenic, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
5301	NM_004715.5(CTDP1):c.863+389C>T	CTDP1	Pathogenic	criteria provided, multiple submitters, no conflicts
252944	NM_021954.4(GJA3):c.56C>T (p.Thr19Met)	GJA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1163617	NM_004715.5(CTDP1):c.1219T>C (p.Trp407Arg)	CTDP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1978365	NM_004715.5(CTDP1):c.1023A>G (p.Arg341=)	CTDP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3237546	NM_004715.5(CTDP1):c.773-9T>G	CTDP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779190	NC_000013.11:g.76901331_76901334del		Uncertain significance	criteria provided, single submitter
1206052	NM_004715.5(CTDP1):c.431C>T (p.Pro144Leu)	CTDP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1495701	NM_004715.5(CTDP1):c.220G>C (p.Val74Leu)	CTDP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805787	NM_004715.5(CTDP1):c.1915A>G (p.Ile639Val)	CTDP1	Uncertain significance	criteria provided, single submitter
2158235	NM_004715.5(CTDP1):c.398A>G (p.Gln133Arg)	CTDP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2158247	NM_004715.5(CTDP1):c.2417+4C>T	CTDP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2419156	NM_004715.5(CTDP1):c.2726C>T (p.Ala909Val)	CTDP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
392399	NM_004715.5(CTDP1):c.440C>T (p.Thr147Met)	CTDP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
808410	NM_004715.5(CTDP1):c.668C>T (p.Thr223Met)	CTDP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
128865	NM_004715.5(CTDP1):c.2817T>C (p.Asp939=)	CTDP1	Benign	criteria provided, multiple submitters, no conflicts
193292	NM_004715.5(CTDP1):c.181T>G (p.Ser61Ala)	CTDP1	Benign	criteria provided, multiple submitters, no conflicts
286855	NM_004715.5(CTDP1):c.1461G>A (p.Pro487=)	CTDP1	Benign	criteria provided, multiple submitters, no conflicts
518282	NM_004715.5(CTDP1):c.978G>A (p.Thr326=)	CTDP1	Benign	criteria provided, multiple submitters, no conflicts
769941	NM_004715.5(CTDP1):c.2070C>T (p.Gly690=)	CTDP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
777336	NM_004715.5(CTDP1):c.492+7C>T	CTDP1	Benign	criteria provided, multiple submitters, no conflicts
803507	NM_004715.5(CTDP1):c.2418-207_2418-165dup	CTDP1	Benign	criteria provided, single submitter
931410	NM_004715.5(CTDP1):c.2649G>A (p.Glu883=)	CTDP1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CTDP1	Definitive	Autosomal recessive	congenital cataracts-facial dysmorphism-neuropathy syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTDP1	Orphanet:48431	Congenital cataracts-facial dysmorphism-neuropathy syndrome
GJA3	Orphanet:98984	Pulverulent cataract
GJA3	Orphanet:98991	Early-onset nuclear cataract
GJA3	Orphanet:98993	Early-onset posterior polar cataract

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
CTDP1	HGNC:2498	ENSG00000060069	Q9Y5B0	RNA polymerase II subunit A C-terminal domain phosphatase	gencc,clinvar
GJA3	HGNC:4277	ENSG00000121743	Q9Y6H8	Gap junction alpha-3 protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTDP1	RNA polymerase II subunit A C-terminal domain phosphatase	Processively dephosphorylates ‘Ser-2’ and ‘Ser-5’ of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit.
GJA3	Gap junction alpha-3 protein	Structural component of lens fiber gap junctions.

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)
CTDP1	Other/Unknown	no		BRCT_dom, FCP1_dom, FCP1_euk
GJA3	Other/Unknown	no		Connexin, Connexin46, Connexin_N

Expression context

Cohort genes with no expression data: 0.

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
left testis	1
right testis	1
skin of leg	1
heart right ventricle	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTDP1	225	ubiquitous	yes	left testis, right testis, skin of leg
GJA3	75	broad	yes	left ventricle myocardium, heart right ventricle, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTDP1	2,122
GJA3	449

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTDP1	Q9Y5B0	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GJA3	Q9Y6H8	69.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Abortive elongation of HIV-1 transcript in the absence of Tat	1	248.3×	0.011	CTDP1
Pausing and recovery of Tat-mediated HIV elongation	1	184.2×	0.011	CTDP1
Tat-mediated HIV elongation arrest and recovery	1	184.2×	0.011	CTDP1
HIV elongation arrest and recovery	1	173.0×	0.011	CTDP1
Pausing and recovery of HIV elongation	1	173.0×	0.011	CTDP1
Formation of the Early Elongation Complex	1	167.9×	0.011	CTDP1
Formation of the HIV-1 Early Elongation Complex	1	167.9×	0.011	CTDP1
Gap junction assembly	1	146.4×	0.011	GJA3
Formation of HIV-1 elongation complex containing HIV-1 Tat	1	129.8×	0.011	CTDP1
Tat-mediated elongation of the HIV-1 transcript	1	129.8×	0.011	CTDP1
Formation of HIV elongation complex in the absence of HIV Tat	1	124.1×	0.011	CTDP1
Formation of RNA Pol II elongation complex	1	96.8×	0.012	CTDP1
RNA Polymerase II Transcription Elongation	1	96.8×	0.012	CTDP1
TP53 Regulates Transcription of DNA Repair Genes	1	90.6×	0.012	CTDP1
RNA Polymerase II Pre-transcription Events	1	68.8×	0.014	CTDP1

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
gap junction-mediated intercellular transport	1	1404.3×	0.005	GJA3
negative regulation of cell growth involved in cardiac muscle cell development	1	702.2×	0.005	CTDP1
exit from mitosis	1	526.6×	0.005	CTDP1
host-mediated activation of viral transcription	1	443.5×	0.005	CTDP1
transcription elongation by RNA polymerase II	1	221.7×	0.008	CTDP1
protein dephosphorylation	1	110.9×	0.013	CTDP1
visual perception	1	39.8×	0.032	GJA3
cell-cell signaling	1	34.8×	0.032	GJA3
cell division	1	23.1×	0.043	CTDP1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTDP1	0	0
GJA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CTDP1, GJA3

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)
CTDP1	0	—
GJA3	0	—

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
NCT01902940	Not specified	COMPLETED	Natural History in CCFDN and IBM Syndromes