TELO2-related intellectual disability-neurodevelopmental disorder

Summary

TELO2-related intellectual disability-neurodevelopmental disorder (MONDO:0014848) is a disease caused by TELO2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TELO2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 45
• Phenotypes (HPO): 52

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

52 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0002141	Gait imbalance	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0011451	Congenital microcephaly	Very frequent (80-99%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001344	Absent speech	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0002540	Inability to walk	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004692	4-5 toe syndactyly	Frequent (30-79%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0030084	Clinodactyly	Frequent (30-79%)
HP:0030962	Abnormal morphology of the great vessels	Frequent (30-79%)
HP:0100022	Abnormality of movement	Frequent (30-79%)
HP:0100704	Cerebral visual impairment	Frequent (30-79%)
HP:0000081	Duplicated collecting system	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000308	Microretrognathia	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000510	Rod-cone dystrophy	Occasional (5-29%)
HP:0000519	Developmental cataract	Occasional (5-29%)
HP:0000582	Upslanted palpebral fissure	Occasional (5-29%)
HP:0000592	Blue sclerae	Occasional (5-29%)
HP:0000768	Pectus carinatum	Occasional (5-29%)
HP:0001182	Tapered finger	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001583	Rotary nystagmus	Occasional (5-29%)
HP:0001734	Annular pancreas	Occasional (5-29%)
HP:0001773	Short foot	Occasional (5-29%)
HP:0001800	Hypoplastic toenails	Occasional (5-29%)
HP:0001838	Rocker bottom foot	Occasional (5-29%)
HP:0001845	Overlapping toe	Occasional (5-29%)
HP:0002714	Downturned corners of mouth	Occasional (5-29%)
HP:0002751	Kyphoscoliosis	Occasional (5-29%)
HP:0003273	Hip contracture	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0006380	Knee flexion contracture	Occasional (5-29%)
HP:0006979	Sleep-wake cycle disturbance	Occasional (5-29%)
HP:0007598	Bilateral single transverse palmar creases	Occasional (5-29%)
HP:0008513	Bilateral conductive hearing impairment	Occasional (5-29%)
HP:0008780	Congenital bilateral hip dislocation	Occasional (5-29%)
HP:0010296	Ankyloglossia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	TELO2-related intellectual disability-neurodevelopmental disorder
Mondo ID	MONDO:0014848
OMIM	616954
Orphanet	488642
UMLS	C4310778
MedGen	934745
GARD	0017898
Is cancer (heuristic)	no

Also known as: YHFS · you-Hoover-Fong syndrome

Data availability: 45 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 › TELO2-related intellectual disability-neurodevelopmental disorder

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, 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, 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

45 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 9 conflicting classifications of pathogenicity, 8 benign, 5 pathogenic, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
236230	NM_016111.3(TELO2):c.[514C>T;2034+1G>A]		Pathogenic	criteria provided, single submitter
1686256	NM_016111.4(TELO2):c.1825C>T (p.Arg609Cys)	TELO2	Pathogenic	criteria provided, single submitter
1927535	NM_016111.4(TELO2):c.1207C>T (p.Arg403Ter)	TELO2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236225	NM_016111.4(TELO2):c.1100G>T (p.Cys367Phe)	TELO2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236229	NM_016111.4(TELO2):c.1826G>A (p.Arg609His)	TELO2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3339339	NM_016111.4(TELO2):c.1612_1621dup (p.Leu541delinsProTer)	TELO2	Pathogenic	criteria provided, single submitter
3907641	NM_016111.4(TELO2):c.434del (p.Thr145fs)	TELO2	Pathogenic	criteria provided, single submitter
4532811	NM_016111.4(TELO2):c.800_801del (p.Val267fs)	TELO2	Pathogenic	criteria provided, multiple submitters, no conflicts
1325187	NM_016111.4(TELO2):c.682+1G>A	TELO2	Likely pathogenic	criteria provided, single submitter
3339225	NM_016111.4(TELO2):c.2226+1G>C	TELO2	Likely pathogenic	criteria provided, single submitter
3367131	NM_016111.4(TELO2):c.946C>T (p.Gln316Ter)	TELO2	Likely pathogenic	criteria provided, single submitter
4086194	NM_016111.4(TELO2):c.2034+2T>C	TELO2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1207111	NM_016111.4(TELO2):c.1842+5G>A	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1331679	NM_016111.4(TELO2):c.2312T>C (p.Leu771Ser)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
236226	NM_016111.4(TELO2):c.2159A>T (p.Asp720Val)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
236227	NM_016111.4(TELO2):c.2296G>A (p.Val766Met)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
236228	NM_016111.4(TELO2):c.779C>T (p.Pro260Leu)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
392873	NM_016111.4(TELO2):c.194G>C (p.Cys65Ser)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
419090	NM_016111.4(TELO2):c.392G>A (p.Gly131Asp)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
430950	NM_016111.4(TELO2):c.1772T>G (p.Val591Gly)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
737992	NM_016111.4(TELO2):c.238C>A (p.His80Asn)	TELO2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2443337	NM_032776.3(JMJD1C):c.1919del (p.Pro640fs)	JMJD1C	Uncertain significance	criteria provided, single submitter
1029577	NM_016111.4(TELO2):c.2003G>A (p.Arg668Gln)	TELO2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030533	NM_016111.4(TELO2):c.2449G>A (p.Ala817Thr)	TELO2	Uncertain significance	criteria provided, single submitter
1033802	NM_016111.4(TELO2):c.1129C>T (p.Arg377Trp)	TELO2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033803	NM_016111.4(TELO2):c.1382C>T (p.Thr461Met)	TELO2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033804	NM_016111.4(TELO2):c.1476T>G (p.Asp492Glu)	TELO2	Uncertain significance	criteria provided, single submitter
1065502	NM_016111.4(TELO2):c.967G>C (p.Ala323Pro)	TELO2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1676226	NM_016111.4(TELO2):c.1747G>A (p.Val583Ile)	TELO2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2081978	NM_016111.4(TELO2):c.830+5G>T	TELO2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
TELO2	Definitive	Autosomal recessive	TELO2-related intellectual disability-neurodevelopmental disorder	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TELO2	Orphanet:488642	TELO2-related intellectual disability-neurodevelopmental disorder
JMJD1C	Orphanet:567	22q11.2 deletion syndrome
JMJD1C	Orphanet:91352	Germinoma of the central nervous system

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
TELO2	HGNC:29099	ENSG00000100726	Q9Y4R8	Telomere length regulation protein TEL2 homolog	gencc,clinvar
JMJD1C	HGNC:12313	ENSG00000171988	Q15652	Jumonji domain-containing protein 1C	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TELO2	Telomere length regulation protein TEL2 homolog	Regulator of the DNA damage response (DDR).
JMJD1C	Jumonji domain-containing protein 1C	Demethylates lysine in proteins, such as STAT3 or MDC1.

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TELO2	Other/Unknown	no		ARM-type_fold, Telomere_length_regulation_dom, TEL2_C_sf
JMJD1C	Enzyme (other)	yes	1.14.11.65	JmjC_dom, LSDs-like, KDM3A/B_DUF7030

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
cerebellar hemisphere	2
right hemisphere of cerebellum	2
right uterine tube	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TELO2	234	ubiquitous	yes	right uterine tube, right hemisphere of cerebellum, cerebellar hemisphere
JMJD1C	291	ubiquitous	marker	calcaneal tendon, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TELO2	1,841
JMJD1C	1,641

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TELO2	Q9Y4R8	3
JMJD1C	Q15652	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.028	JMJD1C
Hemostasis	1	36.0×	0.028	JMJD1C

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
‘de novo’ cotranslational protein folding	1	2808.7×	0.001	TELO2
positive regulation of DNA damage checkpoint	1	2106.5×	0.001	TELO2
blood coagulation	1	86.9×	0.023	JMJD1C
protein stabilization	1	33.4×	0.045	TELO2
regulation of DNA-templated transcription	1	15.8×	0.075	JMJD1C
regulation of transcription by RNA polymerase II	1	5.8×	0.164	JMJD1C

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TELO2	0	0
JMJD1C	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
JMJD1C	2	Binding:2
TELO2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
JMJD1C	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase

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	1	JMJD1C
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TELO2

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)
TELO2	1	—
JMJD1C	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.