Developmental and epileptic encephalopathy, 18

Summary

Developmental and epileptic encephalopathy, 18 (MONDO:0014201) is a disease caused by SZT2 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: SZT2 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 638

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 18
Mondo ID	MONDO:0014201
OMIM	615476
Orphanet	369894
DOID	DOID:0080413
UMLS	C3809624
MedGen	815954
GARD	0013676
Is cancer (heuristic)	no

Also known as: DEE18 · developmental and epileptic encephalopathy 18 · early infantile epileptic encephalopathy without suppression burst · EIEE18 · epileptic encephalopathy, early infantile, 18 · epileptic encephalopathy, early infantile, type 18

Data availability: 638 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › developmental and epileptic encephalopathy, 18

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, 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

600 retrieved; paginated sample, class counts are floors:

350 uncertain significance, 112 likely benign, 40 benign/likely benign, 33 conflicting classifications of pathogenicity, 23 benign, 21 likely pathogenic, 11 pathogenic, 10 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098635	NM_001365999.1(SZT2):c.6976C>T (p.Arg2326Ter)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1375694	NM_001365999.1(SZT2):c.6139C>T (p.Arg2047Ter)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1410681	NM_001365999.1(SZT2):c.3640C>T (p.Arg1214Ter)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456246	NM_001365999.1(SZT2):c.7735C>T (p.Gln2579Ter)	SZT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1990535	NM_001365999.1(SZT2):c.9040C>T (p.Arg3014Ter)	SZT2	Pathogenic	criteria provided, multiple submitters, no conflicts
2585049	NM_001365999.1(SZT2):c.7488dup (p.Asp2497fs)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280377	NM_001365999.1(SZT2):c.4396C>T (p.Arg1466Ter)	SZT2	Pathogenic	criteria provided, multiple submitters, no conflicts
3254920	NM_001365999.1(SZT2):c.203G>A (p.Trp68Ter)	SZT2	Pathogenic	criteria provided, multiple submitters, no conflicts
372895	NM_001365999.1(SZT2):c.6120_6122del (p.Val2041del)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4291100	NM_001365999.1(SZT2):c.9226C>T (p.Arg3076Ter)	SZT2	Pathogenic	criteria provided, single submitter
430047	NM_001365999.1(SZT2):c.2363C>G (p.Ser788Ter)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4536627	NM_001365999.1(SZT2):c.5530G>A (p.Gly1844Arg)	SZT2	Pathogenic	criteria provided, single submitter
4536900	NM_001365999.1(SZT2):c.4503_4594dup (p.Ser1532delinsTrpSerLeuArgValThrGlnSerTer)	SZT2	Pathogenic	criteria provided, single submitter
620537	NM_001365999.1(SZT2):c.5872C>T (p.Arg1958Ter)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
644467	NM_001365999.1(SZT2):c.8811del (p.Ser2938fs)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66996	NM_001365999.1(SZT2):c.73C>T (p.Arg25Ter)	SZT2	Pathogenic	no assertion criteria provided
66997	NM_001365999.1(SZT2):c.2092C>T (p.Gln698Ter)	SZT2	Pathogenic	no assertion criteria provided
66998	NM_001365999.1(SZT2):c.1496G>T (p.Ser499Ile)	SZT2	Pathogenic	no assertion criteria provided
843369	NM_001365999.1(SZT2):c.9874C>T (p.Arg3292Ter)	SZT2	Pathogenic	criteria provided, multiple submitters, no conflicts
932499	NM_001365999.1(SZT2):c.5905C>T (p.Arg1969Ter)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
944876	NM_001365999.1(SZT2):c.8659C>T (p.Arg2887Ter)	SZT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3897895	NM_015284.4:c.[2814+1G>A];[6424C>T]		Likely pathogenic	criteria provided, single submitter
1029531	NM_001365999.1(SZT2):c.5396G>A (p.Trp1799Ter)	SZT2	Likely pathogenic	criteria provided, single submitter
1198403	NM_001365999.1(SZT2):c.153+1G>A	SZT2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723227	NM_001365999.1(SZT2):c.7070T>A (p.Leu2357Ter)	SZT2	Likely pathogenic	criteria provided, single submitter
2584876	NM_001365999.1(SZT2):c.1108_1111del (p.Phe370fs)	SZT2	Likely pathogenic	criteria provided, single submitter
2690762	NM_001365999.1(SZT2):c.1513C>T (p.Gln505Ter)	SZT2	Likely pathogenic	criteria provided, single submitter
3062045	NM_001365999.1(SZT2):c.4699del (p.Leu1567fs)	SZT2	Likely pathogenic	criteria provided, single submitter
3236411	NM_001365999.1(SZT2):c.4401+1G>A	SZT2	Likely pathogenic	criteria provided, single submitter
3341085	NM_001365999.1(SZT2):c.8589del (p.His2863fs)	SZT2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 10 · 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
SZT2	Definitive	Autosomal recessive	developmental and epileptic encephalopathy, 18	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SZT2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SZT2	HGNC:29040	ENSG00000198198	Q5T011	KICSTOR complex protein SZT2	gencc,clinvar
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
HYI	HGNC:26948	ENSG00000178922	Q5T013	Putative hydroxypyruvate isomerase	clinvar
SZT2-AS1	HGNC:41225	ENSG00000229372		SZT2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SZT2	KICSTOR complex protein SZT2	As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
HYI	Putative hydroxypyruvate isomerase	Catalyzes the reversible isomerization between hydroxypyruvate and 2-hydroxy-3-oxopropanoate (also termed tartronate semialdehyde).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SZT2	Other/Unknown	no		SZT2
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
HYI	Other/Unknown	no		Xyl_isomerase-like_TIM-brl, HyI-like, Xyl_isomerase-like_sf
SZT2-AS1	Other/Unknown	no

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
granulocyte	1
sural nerve	1
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
body of pancreas	1
left ovary	1
right lobe of liver	1
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SZT2	238	ubiquitous	marker	colonic epithelium, sural nerve, granulocyte
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
HYI	267	ubiquitous	yes	body of pancreas, right lobe of liver, left ovary
SZT2-AS1	119		yes	cortical plate, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERT	5,717
SZT2	648
HYI	492
SZT2-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TERT	O14746	23
SZT2	Q5T011	9

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HYI	Q5T013	96.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 4 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
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	815.7×	0.021	TERT
Extension of Telomeres	1	300.5×	0.023	TERT
Telomere Extension By Telomerase	1	228.4×	0.023	TERT
Telomere Maintenance	1	184.2×	0.023	TERT
Chromosome Maintenance	1	105.7×	0.025	TERT
Amino acids regulate mTORC1	1	100.2×	0.025	SZT2
MITF-M-dependent gene expression	1	90.6×	0.025	TERT
Cellular response to starvation	1	82.8×	0.025	SZT2
Formation of the beta-catenin:TCF transactivating complex	1	60.1×	0.025	TERT
TCF dependent signaling in response to WNT	1	58.9×	0.025	TERT
MITF-M-regulated melanocyte development	1	57.1×	0.025	TERT
Signaling by WNT	1	56.0×	0.025	TERT
Cellular responses to stress	1	18.4×	0.066	SZT2
Cell Cycle	1	18.0×	0.066	TERT
Cellular responses to stimuli	1	15.7×	0.071	SZT2
Developmental Biology	1	7.2×	0.142	TERT
Signal Transduction	1	5.1×	0.187	TERT

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
RNA-templated transcription	1	5617.3×	0.001	TERT
DNA strand elongation	1	5617.3×	0.001	TERT
siRNA transcription	1	5617.3×	0.001	TERT
regulation of superoxide dismutase activity	1	5617.3×	0.001	SZT2
positive regulation of transdifferentiation	1	5617.3×	0.001	TERT
RNA-templated DNA biosynthetic process	1	2808.7×	0.002	TERT
positive regulation of hair cycle	1	2808.7×	0.002	TERT
glyoxylate metabolic process	1	936.2×	0.005	HYI
positive regulation of protein localization to nucleolus	1	936.2×	0.005	TERT
corpus callosum morphogenesis	1	802.5×	0.005	SZT2
establishment of protein localization to telomere	1	702.2×	0.005	TERT
siRNA processing	1	624.1×	0.006	TERT
telomere maintenance via recombination	1	510.7×	0.006	TERT
protein localization to lysosome	1	351.1×	0.008	SZT2
replicative senescence	1	330.4×	0.008	TERT
positive regulation of vascular associated smooth muscle cell migration	1	330.4×	0.008	TERT
DNA biosynthetic process	1	267.5×	0.009	TERT
telomere maintenance via telomerase	1	244.2×	0.009	TERT
response to cadmium ion	1	244.2×	0.009	TERT
pigmentation	1	234.1×	0.009	SZT2
negative regulation of cellular senescence	1	216.1×	0.009	TERT
positive regulation of stem cell proliferation	1	175.5×	0.011	TERT
negative regulation of endothelial cell apoptotic process	1	165.2×	0.011	TERT
positive regulation of D-glucose import across plasma membrane	1	151.8×	0.012	TERT
positive regulation of vascular associated smooth muscle cell proliferation	1	144.0×	0.012	TERT
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	137.0×	0.012	TERT
positive regulation of G1/S transition of mitotic cell cycle	1	133.8×	0.012	TERT
positive regulation of Wnt signaling pathway	1	127.7×	0.012	TERT
cellular response to glucose starvation	1	112.3×	0.013	SZT2
negative regulation of TORC1 signaling	1	108.0×	0.013	SZT2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) 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
TERT	BERBERINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TERT	10	4
SZT2	0	0
HYI	0	0
SZT2-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT
ALLICIN	2	TERT
OLEIC ACID	2	TERT
ETHACRIDINE	2	TERT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TERT	391	Binding:389, Functional:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TERT	391

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

10 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)
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT
ALLICIN	2	TERT
OLEIC ACID	2	TERT
ETHACRIDINE	2	TERT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TERT
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	3	SZT2, HYI, SZT2-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SZT2	0	—
HYI	0	—
SZT2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.