Dyskeratosis congenita, autosomal dominant 2

Summary

Dyskeratosis congenita, autosomal dominant 2 (MONDO:0013521) is a disease caused by TERT (GenCC Definitive), with 7 cohort genes.

At a glance

• Causal gene: TERT (GenCC Definitive)
• Cohort genes: 7
• ClinVar variants: 2,802

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyskeratosis congenita, autosomal dominant 2
Mondo ID	MONDO:0013521
OMIM	613989
DOID	DOID:0070016
NCIT	C176922
UMLS	C3151443
MedGen	462793
GARD	0015741
Is cancer (heuristic)	no

Also known as: DKCA2 · dyskeratosis congenita, autosomal dominant 2 · dyskeratosis congenita, autosomal dominant type 2

Data availability: 2,802 ClinVar variants · 11 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › dyskeratosis congenita, autosomal dominant 2

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

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:

301 uncertain significance, 228 likely benign, 41 conflicting classifications of pathogenicity, 18 pathogenic, 6 likely pathogenic, 3 pathogenic/likely pathogenic, 2 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070657	NM_198253.3(TERT):c.198dup (p.Ala67fs)	LOC110806263	Pathogenic	criteria provided, single submitter
12738	NM_198253.3(TERT):c.219+1G>A	LOC110806263	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1381898	NM_198253.3(TERT):c.247C>T (p.Arg83Ter)	LOC110806263	Pathogenic	criteria provided, single submitter
1418828	NM_198253.3(TERT):c.10_11dup (p.Pro5fs)	LOC110806263	Pathogenic	criteria provided, single submitter
1069288	NM_198253.3(TERT):c.1314del (p.Glu439fs)	TERT	Pathogenic	criteria provided, single submitter
1073945	NM_198253.3(TERT):c.1424del (p.Pro475fs)	TERT	Pathogenic	criteria provided, single submitter
1074267	NC_000005.9:g.(?1253843)(1297488_?)del	TERT	Pathogenic	criteria provided, single submitter
1074268	NC_000005.9:g.(?1287194)(1297488_?)del	TERT	Pathogenic	criteria provided, single submitter
1075528	NM_198253.3(TERT):c.3235del (p.Leu1079fs)	TERT	Pathogenic	criteria provided, single submitter
12735	NM_198253.3(TERT):c.2706G>C (p.Lys902Asn)	TERT	Pathogenic	no assertion criteria provided
12736	NM_198253.3(TERT):c.2594G>A (p.Arg865His)	TERT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1357479	NM_198253.3(TERT):c.923dup (p.Ser309fs)	TERT	Pathogenic	criteria provided, single submitter
1379443	NM_198253.3(TERT):c.1122del (p.Thr375fs)	TERT	Pathogenic	criteria provided, single submitter
1379483	NM_198253.3(TERT):c.2315_2330del (p.Tyr772fs)	TERT	Pathogenic	criteria provided, single submitter
1397003	NM_198253.3(TERT):c.598G>T (p.Glu200Ter)	TERT	Pathogenic	criteria provided, multiple submitters, no conflicts
1421091	NM_198253.3(TERT):c.767G>A (p.Trp256Ter)	TERT	Pathogenic	criteria provided, single submitter
1434641	NM_198253.3(TERT):c.1871_1872dup (p.Pro625fs)	TERT	Pathogenic	criteria provided, single submitter
1435798	NM_198253.3(TERT):c.1612G>T (p.Glu538Ter)	TERT	Pathogenic	criteria provided, single submitter
1437767	NM_198253.3(TERT):c.996del (p.Tyr333fs)	TERT	Pathogenic	criteria provided, single submitter
1457059	NM_198253.3(TERT):c.2461del (p.Arg821fs)	TERT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459137	NM_198253.3(TERT):c.329del (p.Gly110fs)	TERT	Pathogenic	criteria provided, single submitter
1065578	NM_198253.3(TERT):c.3026C>T (p.Ala1009Val)	TERT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067497	NM_198253.3(TERT):c.2970+2T>G	TERT	Likely pathogenic	criteria provided, single submitter
1338417	NM_198253.3(TERT):c.3157+1G>T	TERT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1348881	NC_000005.9:g.(?1282524)(1282759_?)dup	TERT	Likely pathogenic	criteria provided, single submitter
1485756	NM_198253.3(TERT):c.3118G>A (p.Ala1040Thr)	TERT	Likely pathogenic	criteria provided, single submitter
1502782	NM_198253.3(TERT):c.2286+1G>A	TERT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1156551	NM_198253.3(TERT):c.171C>T (p.Cys57=)	LOC110806263	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1299388	NM_198253.3(TERT):c.-124C>T	LOC110806263	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1402275	NM_198253.3(TERT):c.227G>C (p.Cys76Ser)	LOC110806263	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 11 · 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
TERT	Definitive	Autosomal recessive	dyskeratosis congenita, autosomal dominant 2	20

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
SLC6A19	Orphanet:2116	Hartnup disease
SLC6A19	Orphanet:42062	Iminoglycinuria

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gencc,clinvar
NKD2	HGNC:17046	ENSG00000145506	Q969F2	Protein naked cuticle homolog 2	clinvar
ZDHHC11	HGNC:19158	ENSG00000188818	Q9H8X9	Palmitoyltransferase ZDHHC11	clinvar
CLPTM1L	HGNC:24308	ENSG00000049656	Q96KA5	Lipid scramblase CLPTM1L	clinvar
EXOC3-AS1	HGNC:25175	ENSG00000221990	Q8N2X6	Uncharacterized protein EXOC3-AS1	clinvar
SLC6A19	HGNC:27960	ENSG00000174358	Q695T7	Sodium-dependent neutral amino acid transporter B(0)AT1	clinvar
AHRR	HGNC:346	ENSG00000063438	A9YTQ3	Aryl hydrocarbon receptor repressor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
NKD2	Protein naked cuticle homolog 2	Cell autonomous antagonist of the canonical Wnt signaling pathway.
ZDHHC11	Palmitoyltransferase ZDHHC11	Endoplasmic reticulum-localized palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes.
CLPTM1L	Lipid scramblase CLPTM1L	Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to th…
SLC6A19	Sodium-dependent neutral amino acid transporter B(0)AT1	Transporter that mediates resorption of neutral amino acids across the apical membrane of renal and intestinal epithelial cells.
AHRR	Aryl hydrocarbon receptor repressor	Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 6 · 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	6	1.5×	0.221
Transcription factor	1	1.2×	0.595

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
NKD2	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, Nkd-like
ZDHHC11	Other/Unknown	no		Palmitoyltrfase_DHHC, PFA4/ZDH16/20/ERF2-like
CLPTM1L	Other/Unknown	no		CLPTM1
EXOC3-AS1	Other/Unknown	no
SLC6A19	Other/Unknown	no		Na/ntran_symport, Neutral_aa_SLC6, SNS_sf
AHRR	Transcription factor	no		PAS, bHLH_dom, PAS_fold

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
ileal mucosa	2
kidney epithelium	2
olfactory bulb	1
type B pancreatic cell	1
lung	1
right lung	1
upper lobe of left lung	1
cardiac muscle of right atrium	1
right hemisphere of cerebellum	1
right uterine tube	1
right lobe of thyroid gland	1
adenohypophysis	1
buccal mucosa cell	1
primordial germ cell in gonad	1
jejunal mucosa	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
NKD2	130	broad	yes	upper lobe of left lung, right lung, lung
ZDHHC11	251		marker	right uterine tube, cardiac muscle of right atrium, right hemisphere of cerebellum
CLPTM1L	255	ubiquitous	marker	ileal mucosa, kidney epithelium, right lobe of thyroid gland
EXOC3-AS1	188	ubiquitous	yes	primordial germ cell in gonad, adenohypophysis, buccal mucosa cell
SLC6A19	67	tissue_specific	marker	ileal mucosa, kidney epithelium, jejunal mucosa
AHRR	131	ubiquitous	yes	left testis, stromal cell of endometrium, right testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERT	5,717
CLPTM1L	1,606
SLC6A19	975
NKD2	745
AHRR	664
ZDHHC11	401
EXOC3-AS1	32

Intra-cohort edges

A	B	Sources
CLPTM1L	TERT	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TERT	O14746	23
SLC6A19	Q695T7	21
AHRR	A9YTQ3	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLPTM1L	Q96KA5	78.54
ZDHHC11	Q9H8X9	74.62
NKD2	Q969F2	56.15
EXOC3-AS1	Q8N2X6	50.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 7 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective transport of neurotransmitters by SLC6A19 causes Hartnup disorder (HND)	1	2855.0×	0.005	SLC6A19
Defective transport of amino acids by SLC6A19 causes Hartnup disorder (HND)	1	2855.0×	0.005	SLC6A19
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	407.9×	0.021	TERT
Extension of Telomeres	1	150.3×	0.040	TERT
Telomere Extension By Telomerase	1	114.2×	0.040	TERT
SLC-mediated transport of neurotransmitters	1	102.0×	0.040	SLC6A19
Telomere Maintenance	1	92.1×	0.040	TERT
Amino acid transport across the plasma membrane	1	75.1×	0.043	SLC6A19
Maturation of spike protein	1	66.4×	0.043	ZDHHC11
Chromosome Maintenance	1	52.9×	0.044	TERT
SLC transporter disorders	1	51.0×	0.044	SLC6A19
R-HSA-425366	1	45.3×	0.044	SLC6A19
MITF-M-dependent gene expression	1	45.3×	0.044	TERT
CHD6, CHD7, CHD8, CHD9 subfamily	1	37.1×	0.046	NKD2
Disorders of transmembrane transporters	1	34.8×	0.046	SLC6A19
R-HSA-425393	1	32.4×	0.046	SLC6A19
Formation of the beta-catenin:TCF transactivating complex	1	30.1×	0.046	TERT
TCF dependent signaling in response to WNT	1	29.4×	0.046	TERT
MITF-M-regulated melanocyte development	1	28.6×	0.046	TERT
Signaling by WNT	1	28.0×	0.046	TERT
SLC-mediated transmembrane transport	1	14.8×	0.082	SLC6A19
Cell Cycle	1	9.0×	0.126	TERT
Transport of small molecules	1	6.3×	0.169	SLC6A19
Developmental Biology	1	3.6×	0.270	TERT
Disease	1	3.3×	0.283	SLC6A19
Signal Transduction	1	2.5×	0.339	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 6 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	2808.7×	0.005	TERT
DNA strand elongation	1	2808.7×	0.005	TERT
siRNA transcription	1	2808.7×	0.005	TERT
positive regulation of transdifferentiation	1	2808.7×	0.005	TERT
RNA-templated DNA biosynthetic process	1	1404.3×	0.005	TERT
positive regulation of hair cycle	1	1404.3×	0.005	TERT
Golgi vesicle fusion to target membrane	1	1404.3×	0.005	NKD2
viral life cycle	1	702.2×	0.009	SLC6A19
positive regulation of protein localization to nucleolus	1	468.1×	0.013	TERT
establishment of protein localization to telomere	1	351.1×	0.015	TERT
siRNA processing	1	312.1×	0.015	TERT
telomere maintenance via recombination	1	255.3×	0.017	TERT
positive regulation of protein processing	1	200.6×	0.019	NKD2
peptidyl-L-cysteine S-palmitoylation	1	200.6×	0.019	ZDHHC11
replicative senescence	1	165.2×	0.020	TERT
positive regulation of vascular associated smooth muscle cell migration	1	165.2×	0.020	TERT
neutral amino acid transport	1	147.8×	0.021	SLC6A19
DNA biosynthetic process	1	133.8×	0.022	TERT
telomere maintenance via telomerase	1	122.1×	0.022	TERT
response to cadmium ion	1	122.1×	0.022	TERT
negative regulation of cellular senescence	1	108.0×	0.023	TERT
positive regulation of defense response to virus by host	1	87.8×	0.026	ZDHHC11
positive regulation of stem cell proliferation	1	87.8×	0.026	TERT
negative regulation of endothelial cell apoptotic process	1	82.6×	0.027	TERT
positive regulation of D-glucose import across plasma membrane	1	75.9×	0.028	TERT
positive regulation of vascular associated smooth muscle cell proliferation	1	72.0×	0.028	TERT
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	68.5×	0.028	TERT
positive regulation of G1/S transition of mitotic cell cycle	1	66.9×	0.028	TERT
positive regulation of Wnt signaling pathway	1	63.8×	0.028	TERT
negative regulation of Wnt signaling pathway	1	57.3×	0.031	NKD2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 3 of 7 evidence-associated genes (43%) 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
SLC6A19	1	2
NKD2	0	0
ZDHHC11	0	0
CLPTM1L	0	0
EXOC3-AS1	0	0
AHRR	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
CINROMIDE	2	SLC6A19

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
SLC6A19	4	Functional:3, Binding:1
CLPTM1L	1	Binding:1

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: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

11 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
CINROMIDE	2	SLC6A19

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	1	SLC6A19
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	NKD2, ZDHHC11, CLPTM1L, EXOC3-AS1, AHRR

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CLPTM1L	1	TERT
NKD2	0	—
ZDHHC11	0	—
EXOC3-AS1	0	—
AHRR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.