Progressive myoclonic epilepsy type 3

Summary

Progressive myoclonic epilepsy type 3 (MONDO:0012721) is a disease caused by KCTD7 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: KCTD7 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 421
• Phenotypes (HPO): 22
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001336	Myoclonus	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0007221	Progressive truncal ataxia	Frequent (30-79%)
HP:0007272	Progressive psychomotor deterioration	Frequent (30-79%)
HP:0011166	Focal myoclonic seizure	Frequent (30-79%)
HP:0011188	Focal EEG discharges with secondary generalization	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000504	Abnormality of vision	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000726	Dementia	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001327	Photomyoclonic seizures	Occasional (5-29%)
HP:0002059	Cerebral atrophy	Occasional (5-29%)
HP:0002069	Bilateral tonic-clonic seizure	Occasional (5-29%)
HP:0002073	Progressive cerebellar ataxia	Occasional (5-29%)
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)	Occasional (5-29%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0011185	EEG with focal epileptiform discharges	Occasional (5-29%)
HP:0012462	Chin myoclonus	Occasional (5-29%)
HP:0045084	Limb myoclonus	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	progressive myoclonic epilepsy type 3
Mondo ID	MONDO:0012721
MeSH	C567095
OMIM	611726
Orphanet	263516, 699708
DOID	DOID:0111446
ICD-11	383417276
SNOMED CT	783064000
UMLS	C2673257
MedGen	388595
GARD	0002167
Is cancer (heuristic)	no

Also known as: CLN14 disease · epilepsy progressive myoclonic type 3 · epilepsy, progressive myoclonic 3, with or without intracellular inclusions · epilepsy, progressive myoclonic, 3, with or without intracellular inclusions · EPM 3 · EPM3 · KCTD7 progressive myoclonic epilepsy · neuronal ceroid lipofuscinosis type 14 · PME type 3 · progressive myoclonic epilepsy 3 · progressive myoclonic epilepsy caused by mutation in KCTD7 · progressive myoclonic epilepsy due to KCTD7 deficiency · progressive myoclonic epilepsy type 3 · progressive myoclonus epilepsy type 3

Data availability: 421 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › progressive myoclonic epilepsy type 3

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, 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

421 retrieved; paginated sample, class counts are floors:

198 uncertain significance, 140 likely benign, 24 conflicting classifications of pathogenicity, 20 pathogenic, 19 benign, 11 likely pathogenic, 4 benign/likely benign, 3 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; affects, 1 uncertain significance; affects

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069708	NM_153033.5(KCTD7):c.339_340del (p.Asp115fs)	KCTD7	Pathogenic	criteria provided, multiple submitters, no conflicts
1075621	NC_000007.13:g.(?66094052)(66104219_?)del	KCTD7	Pathogenic	criteria provided, single submitter
1252047	NM_153033.5(KCTD7):c.696del (p.Phe232fs)	KCTD7	Pathogenic	no assertion criteria provided
1332817	NM_153033.5(KCTD7):c.205C>G (p.Leu69Val)	KCTD7	Pathogenic	criteria provided, single submitter
1405546	NM_153033.5(KCTD7):c.388C>T (p.Gln130Ter)	KCTD7	Pathogenic	criteria provided, single submitter
1427810	NM_153033.5(KCTD7):c.827A>G (p.Tyr276Cys)	KCTD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452016	NC_000007.13:g.(?66103220)(66104219_?)del	KCTD7	Pathogenic	criteria provided, single submitter
2164909	NM_153033.5(KCTD7):c.367C>T (p.Arg123Ter)	KCTD7	Pathogenic	criteria provided, single submitter
2722390	NM_153033.5(KCTD7):c.130dup (p.Leu44fs)	KCTD7	Pathogenic	criteria provided, single submitter
3245776	NC_000007.13:g.(?66068499)(66098288_?)del	KCTD7	Pathogenic	criteria provided, single submitter
3652794	NM_153033.5(KCTD7):c.514G>T (p.Glu172Ter)	KCTD7	Pathogenic	criteria provided, single submitter
36926	NM_153033.5(KCTD7):c.550C>T (p.Arg184Cys)	KCTD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37009	NM_153033.5(KCTD7):c.594del (p.Ile199fs)	KCTD7	Pathogenic	criteria provided, single submitter
37011	NM_153033.5(KCTD7):c.818A>T (p.Asn273Ile)	KCTD7	Pathogenic	no assertion criteria provided
37012	NM_153033.5(KCTD7):c.343G>T (p.Asp115Tyr)	KCTD7	Pathogenic	no assertion criteria provided
37013	NM_153033.5(KCTD7):c.322C>A (p.Leu108Met)	KCTD7	Pathogenic	no assertion criteria provided
379332	NM_153033.5(KCTD7):c.631C>T (p.Arg211Ter)	KCTD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4731709	NM_153033.5(KCTD7):c.338C>G (p.Ser113Ter)	KCTD7	Pathogenic	criteria provided, single submitter
583587	NC_000007.14:g.(?66638233)(66639252_?)del	KCTD7	Pathogenic	criteria provided, single submitter
831752	NC_000007.14:g.(?66629045)(66640414_?)del	KCTD7	Pathogenic	criteria provided, single submitter
843	NM_153033.5(KCTD7):c.295C>T (p.Arg99Ter)	KCTD7	Pathogenic	criteria provided, multiple submitters, no conflicts
860762	NM_153033.5(KCTD7):c.331del (p.Leu111fs)	KCTD7	Pathogenic	criteria provided, single submitter
1452460	NM_153033.5(KCTD7):c.139C>T (p.Gln47Ter)	LOC129998533	Pathogenic	criteria provided, single submitter
1188829	NM_153033.5(KCTD7):c.685G>T (p.Asp229Tyr)	KCTD7	Likely pathogenic	no assertion criteria provided
1324611	NM_153033.5(KCTD7):c.493+2_493+6del	KCTD7	Likely pathogenic	criteria provided, single submitter
1332794	NM_153033.5(KCTD7):c.458G>C (p.Arg153Pro)	KCTD7	Likely pathogenic	criteria provided, single submitter
2168099	NM_153033.5(KCTD7):c.520G>A (p.Ala174Thr)	KCTD7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2502292	NM_153033.5(KCTD7):c.207_214del (p.Cys71fs)	KCTD7	Likely pathogenic	criteria provided, single submitter
2671704	NM_153033.5(KCTD7):c.294C>T (p.Asp98=)	KCTD7	Likely pathogenic	criteria provided, single submitter
3067831	NM_153033.5(KCTD7):c.835_840del (p.Arg279_Pro280del)	KCTD7	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
KCTD7	Definitive	Autosomal recessive	progressive myoclonic epilepsy type 3	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCTD7	Orphanet:263516	Progressive myoclonic epilepsy type 3
KCTD7	Orphanet:699708	CLN14 disease
CLN3	Orphanet:699780	Juvenile CLN3 disease
CLN3	Orphanet:699796	Protracted juvenile CLN3 disease

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
KCTD7	HGNC:21957	ENSG00000243335	Q96MP8	BTB/POZ domain-containing protein KCTD7	gencc,clinvar
CLN3	HGNC:2074	ENSG00000188603	Q13286	Battenin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCTD7	BTB/POZ domain-containing protein KCTD7	May be involved in the control of excitability of cortical neurons.
CLN3	Battenin	Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome prote…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCTD7	Other/Unknown	no		BTB/POZ_dom, T1-type_BTB, SKP1/BTB/POZ_sf
CLN3	Transporter	yes		Battenin_disease_Cln3, Battenin_disease_Cln3_subgr, MFS_trans_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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
C1 segment of cervical spinal cord	1
cortical plate	1
ganglionic eminence	1
granulocyte	1
mucosa of transverse colon	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCTD7	261	ubiquitous	yes	cortical plate, ganglionic eminence, C1 segment of cervical spinal cord
CLN3	134	ubiquitous	marker	mucosa of transverse colon, placenta, granulocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLN3	1,613
KCTD7	981

Intra-cohort edges

A	B	Sources
CLN3	KCTD7	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLN3	Q13286	81.81
KCTD7	Q96MP8	81.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Glycosphingolipid transport	1	713.8×	0.011	CLN3
Class I MHC mediated antigen processing & presentation	1	35.0×	0.106	KCTD7
Neddylation	1	23.7×	0.106	KCTD7
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.106	KCTD7
Adaptive Immune System	1	14.9×	0.106	KCTD7
Post-translational protein modification	1	9.6×	0.135	KCTD7
Immune System	1	6.5×	0.155	KCTD7
Metabolism of proteins	1	6.2×	0.155	KCTD7

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
obsolete phagosome-lysosome docking	1	8426.0×	0.002	CLN3
regulation of cellular response to osmotic stress	1	8426.0×	0.002	CLN3
regulation of arginine biosynthetic process	1	8426.0×	0.002	CLN3
renal potassium excretion	1	4213.0×	0.002	CLN3
regulation of phagosome maturation	1	4213.0×	0.002	CLN3
regulation of autophagosome size	1	2808.7×	0.002	CLN3
glycolipid transport	1	2808.7×	0.002	CLN3
regulation of modification of synaptic structure	1	2808.7×	0.002	CLN3
positive regulation of caveolin-mediated endocytosis	1	2106.5×	0.003	CLN3
lysosomal lumen pH elevation	1	1685.2×	0.003	CLN3
positive regulation of pinocytosis	1	1685.2×	0.003	CLN3
positive regulation of Golgi to plasma membrane protein transport	1	1404.3×	0.003	CLN3
plasma membrane raft organization	1	1404.3×	0.003	CLN3
intracellular glutamate homeostasis	1	1404.3×	0.003	KCTD7
regulation of autophagosome maturation	1	1404.3×	0.003	CLN3
intracellular water homeostasis	1	1203.7×	0.003	CLN3
glycerophospholipid biosynthetic process	1	936.2×	0.003	CLN3
membrane hyperpolarization	1	936.2×	0.003	KCTD7
ceramide transport	1	766.0×	0.003	CLN3
regulation of protein processing	1	766.0×	0.003	CLN3
Golgi to lysosome transport	1	766.0×	0.003	CLN3
blood vessel endothelial cell migration	1	702.2×	0.003	CLN3
L-arginine transmembrane transport	1	702.2×	0.003	CLN3
regulation of fibroblast migration	1	648.1×	0.003	CLN3
ionotropic glutamate receptor signaling pathway	1	648.1×	0.003	CLN3
phagosome-lysosome fusion	1	648.1×	0.003	CLN3
amyloid precursor protein catabolic process	1	601.9×	0.003	CLN3
autophagosome-lysosome fusion	1	601.9×	0.003	CLN3
regulation of short-term neuronal synaptic plasticity	1	561.7×	0.003	CLN3
regulation of synaptic transmission, GABAergic	1	526.6×	0.003	CLN3

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
KCTD7	0	0
CLN3	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	1	CLN3
E	Difficult family or no structure, no drug	1	KCTD7

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)
KCTD7	0	—
CLN3	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
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database