Dyskeratosis congenita, autosomal dominant 3

Summary

Dyskeratosis congenita, autosomal dominant 3 (MONDO:0013522) is a disease caused by TINF2 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: TINF2 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 83

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyskeratosis congenita, autosomal dominant 3
Mondo ID	MONDO:0013522
OMIM	613990
DOID	DOID:0070018
NCIT	C176923
UMLS	C3151445
MedGen	462795
GARD	0015742
Is cancer (heuristic)	no

Also known as: DKCA3 · dyskeratosis congenita, autosomal dominant 3 · dyskeratosis congenita, autosomal dominant type 3

Data availability: 83 ClinVar variants · 4 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 3

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 2, 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

83 retrieved; paginated sample, class counts are floors:

43 uncertain significance, 12 conflicting classifications of pathogenicity, 11 benign/likely benign, 8 pathogenic, 5 benign, 2 likely benign, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
31541	NM_001099274.3(TINF2):c.805C>T (p.Gln269Ter)	TINF2	Pathogenic	no assertion criteria provided
31543	NM_001099274.3(TINF2):c.811C>T (p.Gln271Ter)	TINF2	Pathogenic	no assertion criteria provided
37090	NM_001099274.3(TINF2):c.826del (p.Arg276fs)	TINF2	Pathogenic	no assertion criteria provided
4056134	NM_001099274.3(TINF2):c.848_849dup (p.Thr284fs)	TINF2	Pathogenic	criteria provided, single submitter
5624	NM_001099274.3(TINF2):c.838A>G (p.Lys280Glu)	TINF2	Pathogenic	criteria provided, single submitter
5625	NM_001099274.3(TINF2):c.845G>A (p.Arg282His)	TINF2	Pathogenic	criteria provided, multiple submitters, no conflicts
5626	NM_001099274.3(TINF2):c.844C>A (p.Arg282Ser)	TINF2	Pathogenic	criteria provided, single submitter
5627	NM_001099274.3(TINF2):c.844C>T (p.Arg282Cys)	TINF2	Pathogenic	criteria provided, multiple submitters, no conflicts
3237357	NM_001099274.3(TINF2):c.865C>G (p.Pro289Ala)	TINF2	Likely pathogenic	criteria provided, single submitter
3576544	NM_001099274.3(TINF2):c.848C>T (p.Pro283Leu)	TINF2	Likely pathogenic	criteria provided, single submitter
312957	NM_001099274.3(TINF2):c.62A>G (p.Gln21Arg)	LOC130055403	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
417880	NM_001099274.3(TINF2):c.81C>A (p.Cys27Ter)	LOC130055403	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312958	NM_001099274.3(TINF2):c.-50A>G	LOC130055404	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
38918	NM_001099274.3(TINF2):c.841G>A (p.Glu281Lys)	TGM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
280299	NM_001099274.3(TINF2):c.936C>A (p.Tyr312Ter)	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312948	NM_001099274.3(TINF2):c.1074T>C (p.Asp358=)	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312953	NM_001099274.3(TINF2):c.507+5C>T	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
38916	NM_001099274.3(TINF2):c.734C>A (p.Ser245Tyr)	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
662182	NM_001099274.3(TINF2):c.1307C>T (p.Ala436Val)	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
846888	NM_001099274.3(TINF2):c.318G>C (p.Lys106Asn)	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
880974	NM_001099274.3(TINF2):c.253C>G (p.His85Asp)	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
882334	NM_001099274.3(TINF2):c.30A>G (p.Ala10=)	TINF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1422121	NM_001099274.3(TINF2):c.166C>G (p.Arg56Gly)	LOC130055403	Uncertain significance	criteria provided, multiple submitters, no conflicts
1467172	NM_001099274.3(TINF2):c.128C>A (p.Ala43Asp)	LOC130055403	Uncertain significance	criteria provided, multiple submitters, no conflicts
3001449	NM_001099274.3(TINF2):c.73G>A (p.Gly25Arg)	LOC130055403	Uncertain significance	criteria provided, multiple submitters, no conflicts
3576546	NM_001099274.3(TINF2):c.106G>A (p.Glu36Lys)	LOC130055403	Uncertain significance	criteria provided, multiple submitters, no conflicts
312960	NM_001099274.3(TINF2):c.-93T>C	LOC130055404	Uncertain significance	criteria provided, single submitter
312963	NM_001099274.3(TINF2):c.-223C>G	LOC130055404	Uncertain significance	criteria provided, single submitter
882601	NM_001099274.3(TINF2):c.-130A>G	LOC130055404	Uncertain significance	criteria provided, single submitter
883384	NM_001099274.3(TINF2):c.-233T>G	LOC130055404	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
TINF2	Definitive	Autosomal dominant	dyskeratosis congenita, autosomal dominant 3	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TINF2	Orphanet:1775	Dyskeratosis congenita
TINF2	Orphanet:3088	Revesz syndrome
TINF2	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TGM1	Orphanet:100976	Bathing suit ichthyosis
TGM1	Orphanet:281122	Self-improving collodion baby
TGM1	Orphanet:281127	Acral self-healing collodion baby
TGM1	Orphanet:313	Lamellar ichthyosis
TGM1	Orphanet:79394	Congenital ichthyosiform erythroderma
TNXB	Orphanet:230839	Classical-like Ehlers-Danlos syndrome type 1
TNXB	Orphanet:289365	Familial vesicoureteral reflux

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TINF2	HGNC:11824	ENSG00000092330	Q9BSI4	TERF1-interacting nuclear factor 2	gencc,clinvar
TGM1	HGNC:11777	ENSG00000092295	P22735	Protein-glutamine gamma-glutamyltransferase K	clinvar
TNXB	HGNC:11976	ENSG00000168477	P22105	Tenascin-X	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TINF2	TERF1-interacting nuclear factor 2	Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection.
TGM1	Protein-glutamine gamma-glutamyltransferase K	Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.
TNXB	Tenascin-X	Appears to mediate interactions between cells and the extracellular matrix.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
Antibody/Immunoglobulin	2	19.5×	0.007
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TINF2	Other/Unknown	no		TINF2_N, TINF2
TGM1	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
TNXB	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right adrenal gland	2
right adrenal gland cortex	2
granulocyte	1
esophagus mucosa	1
lower esophagus mucosa	1
skin of leg	1
apex of heart	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TINF2	144	ubiquitous	marker	granulocyte, right adrenal gland, right adrenal gland cortex
TGM1	135	broad	marker	lower esophagus mucosa, esophagus mucosa, skin of leg
TNXB	134	ubiquitous	marker	apex of heart, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TGM1	1,978
TINF2	1,769
TNXB	1,335

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TINF2	Q9BSI4	3
TNXB	P22105	3
TGM1	P22735	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Telomere C-strand synthesis initiation	1	271.9×	0.022	TINF2
Processive synthesis on the C-strand of the telomere	1	253.8×	0.022	TINF2
Telomere C-strand (Lagging Strand) Synthesis	1	253.8×	0.022	TINF2
Removal of the Flap Intermediate from the C-strand	1	211.5×	0.022	TINF2
Telomere Extension By Telomerase	1	152.3×	0.022	TINF2
Polymerase switching on the C-strand of the telomere	1	141.0×	0.022	TINF2
Packaging Of Telomere Ends	1	73.2×	0.027	TINF2
Recognition and association of DNA glycosylase with site containing an affected purine	1	68.0×	0.027	TINF2
Cleavage of the damaged purine	1	68.0×	0.027	TINF2
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	1	61.4×	0.027	TINF2
Cleavage of the damaged pyrimidine	1	61.4×	0.027	TINF2
Inhibition of DNA recombination at telomere	1	56.0×	0.027	TINF2
DNA Damage/Telomere Stress Induced Senescence	1	54.4×	0.027	TINF2
ECM proteoglycans	1	50.1×	0.027	TNXB
Meiotic synapsis	1	47.0×	0.027	TINF2
Formation of the cornified envelope	1	29.3×	0.040	TGM1
Extracellular matrix organization	1	21.0×	0.052	TNXB
Keratinization	1	18.6×	0.056	TGM1
Developmental Biology	1	4.8×	0.194	TGM1

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
regulation of telomere maintenance via telomere lengthening	1	5617.3×	0.003	TINF2
positive regulation of cell fate determination	1	5617.3×	0.003	TNXB
cell envelope organization	1	1872.4×	0.005	TGM1
telomere assembly	1	1404.3×	0.005	TINF2
positive regulation of collagen fibril organization	1	1404.3×	0.005	TNXB
elastic fiber assembly	1	510.7×	0.008	TNXB
protein localization to chromosome, telomeric region	1	510.7×	0.008	TINF2
telomere capping	1	432.1×	0.008	TINF2
positive regulation of vascular endothelial growth factor signaling pathway	1	374.5×	0.008	TNXB
collagen metabolic process	1	351.1×	0.008	TNXB
cornification	1	351.1×	0.008	TGM1
positive regulation of keratinocyte proliferation	1	330.4×	0.008	TGM1
regulation of JNK cascade	1	295.6×	0.008	TNXB
negative regulation of telomere maintenance via telomerase	1	244.2×	0.009	TINF2
positive regulation of telomere maintenance	1	170.2×	0.012	TINF2
triglyceride metabolic process	1	147.8×	0.012	TNXB
positive regulation of cell cycle	1	147.8×	0.012	TGM1
regulation of cell differentiation	1	144.0×	0.012	TNXB
positive regulation of epithelial to mesenchymal transition	1	106.0×	0.016	TNXB
regulation of cell adhesion	1	102.1×	0.016	TNXB
negative regulation of epithelial cell proliferation	1	96.8×	0.016	TINF2
keratinocyte differentiation	1	82.6×	0.017	TGM1
protein modification process	1	81.4×	0.017	TGM1
collagen fibril organization	1	74.9×	0.018	TNXB
fatty acid metabolic process	1	64.6×	0.020	TNXB
cell-matrix adhesion	1	54.5×	0.022	TNXB
regulation of cell migration	1	52.5×	0.022	TNXB
neuron projection development	1	40.7×	0.028	TNXB
cell-cell adhesion	1	33.8×	0.032	TNXB
actin cytoskeleton organization	1	26.4×	0.040	TNXB

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TINF2	0	0
TGM1	0	0
TNXB	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
TGM1	11	Binding:11

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TGM1	2.3.2.13	protein-glutamine gamma-glutamyltransferase

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

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	2	TGM1, TNXB
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TINF2

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)
TINF2	0	—
TGM1	11	—
TNXB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.