Autosomal dominant keratitis

Summary

Autosomal dominant keratitis (MONDO:0007848) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 119
• Phenotypes (HPO): 16

Clinical features

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000491	Keratitis	Obligate (100%)
HP:0000539	Abnormality of refraction	Frequent (30-79%)
HP:0001104	Macular hypoplasia	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0007750	Hypoplasia of the fovea	Frequent (30-79%)
HP:0007759	Opacification of the corneal stroma	Frequent (30-79%)
HP:0007990	Hypoplastic iris stroma	Frequent (30-79%)
HP:0011496	Corneal neovascularization	Frequent (30-79%)
HP:0025348	Abnormality of the corneal limbus	Frequent (30-79%)
HP:0032107	Limbal stem cell deficiency	Frequent (30-79%)
HP:0000482	Microcornea	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000526	Aniridia	Occasional (5-29%)
HP:0000589	Coloboma	Occasional (5-29%)
HP:0006934	Congenital nystagmus	Occasional (5-29%)
HP:0007633	Bilateral microphthalmos	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant keratitis
Mondo ID	MONDO:0007848
MeSH	C537022
OMIM	148190
Orphanet	2334
DOID	DOID:0111383
ICD-11	682617640
SNOMED CT	715339004
UMLS	C1835698
MedGen	332039
GARD	0003089
Is cancer (heuristic)	no

Also known as: dominantly inherited keratitis · hereditary keratitis · keratitis, autosomal dominant

Data availability: 119 ClinVar variants · 2 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 › autosomal dominant keratitis

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-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, 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

119 retrieved; paginated sample, class counts are floors:

64 uncertain significance, 23 conflicting classifications of pathogenicity, 13 benign/likely benign, 12 benign, 3 likely benign, 2 pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3474	NM_001368894.2(PAX6):c.1310A>T (p.Ter437Leu)	ELP4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279862	NM_001368894.2(PAX6):c.823C>T (p.Arg275Ter)	PAX6	Pathogenic	criteria provided, multiple submitters, no conflicts
3469	NM_001368894.2(PAX6):c.959-2A>T	PAX6	Pathogenic	no assertion criteria provided
3471	NM_001368894.2(PAX6):c.419T>A (p.Val140Asp)	PAX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
304291	NM_000280.4(PAX6):c.*4696G>C	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304292	NM_000280.4(PAX6):c.*4627A>C	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304304	NM_000280.4(PAX6):c.*3746C>T	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304307	NM_000280.4(PAX6):c.*3670C>T	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304308	NM_000280.4(PAX6):c.*3318A>G	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304311	NM_000280.4(PAX6):c.*3168C>T	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304319	NM_000280.4(PAX6):c.*2882T>C	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304324	NM_000280.4(PAX6):c.*2506C>T	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304345	NM_001368894.2(PAX6):c.*891G>A	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304350	NM_001368894.2(PAX6):c.*356T>A	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
878113	NM_000280.4(PAX6):c.*3428C>T	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304365	NM_001368894.2(PAX6):c.-316-8C>G	LOC106014249	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304366	NM_001368894.2(PAX6):c.-368G>A	LOC106014249	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258168	NM_001368894.2(PAX6):c.808-12C>T	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290049	NM_001368894.2(PAX6):c.1179A>C (p.Thr393=)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304346	NM_001368894.2(PAX6):c.*841C>T	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304356	NM_001368894.2(PAX6):c.873G>A (p.Gln291=)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304357	NM_001368894.2(PAX6):c.753G>A (p.Val251=)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304362	NM_001368894.2(PAX6):c.-107C>T	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
623768	NM_001368894.2(PAX6):c.985T>C (p.Leu329=)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
877705	NM_001368894.2(PAX6):c.317G>A (p.Arg106Gln)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
878639	NM_001368894.2(PAX6):c.972A>T (p.Thr324=)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
878640	NM_001368894.2(PAX6):c.909T>C (p.Ser303=)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304294	NM_000280.4(PAX6):c.*4533T>C	ELP4	Uncertain significance	criteria provided, single submitter
304296	NM_000280.4(PAX6):c.*4361T>C	ELP4	Uncertain significance	criteria provided, single submitter
304298	NM_000280.4(PAX6):c.*4128C>T	ELP4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 13 · 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
PAX6	Supportive	Autosomal dominant	autosomal dominant keratitis	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX6	Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome
PAX6	Orphanet:2253	Foveal hypoplasia-presenile cataract syndrome
PAX6	Orphanet:2334	Autosomal dominant keratitis
PAX6	Orphanet:250923	Isolated aniridia
PAX6	Orphanet:35737	Morning glory disc anomaly
PAX6	Orphanet:708	Peters anomaly
PAX6	Orphanet:893	WAGR syndrome
PAX6	Orphanet:98942	Coloboma of choroid and retina
PAX6	Orphanet:98943	Coloboma of eye lens
PAX6	Orphanet:98944	Coloboma of iris
PAX6	Orphanet:98945	Coloboma of macula
PAX6	Orphanet:98946	Coloboma of eyelid
PAX6	Orphanet:98947	Coloboma of optic disc

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
PAX6	HGNC:8620	ENSG00000007372	P26367	Paired box protein Pax-6	gencc,clinvar
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX6	Paired box protein Pax-6	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas.
ELP4	Elongator complex protein 4	Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
palpebral conjunctiva	1
type B pancreatic cell	1
calcaneal tendon	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX6	201	broad	marker	palpebral conjunctiva, type B pancreatic cell, ventricular zone
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971
ELP4	1,740

Intra-cohort edges

A	B	Sources
ELP4	PAX6	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PAX6	P26367	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELP4	Q96EB1	74.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the anterior neural plate	1	519.1×	0.006	PAX6
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	439.2×	0.006	PAX6
Regulation of gene expression in beta cells	1	259.6×	0.006	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	259.6×	0.006	PAX6
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	45.7×	0.025	PAX6
HATs acetylate histones	1	39.6×	0.025	ELP4

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
pancreatic A cell development	1	8426.0×	0.002	PAX6
oligodendrocyte cell fate specification	1	8426.0×	0.002	PAX6
forebrain-midbrain boundary formation	1	8426.0×	0.002	PAX6
somatic motor neuron fate commitment	1	8426.0×	0.002	PAX6
habenula development	1	2808.7×	0.004	PAX6
regulation of asymmetric cell division	1	2106.5×	0.004	PAX6
regulation of timing of cell differentiation	1	2106.5×	0.004	PAX6
ventral spinal cord interneuron specification	1	1404.3×	0.004	PAX6
commitment of neuronal cell to specific neuron type in forebrain	1	1404.3×	0.004	PAX6
salivary gland morphogenesis	1	1203.7×	0.004	PAX6
cerebral cortex regionalization	1	1203.7×	0.004	PAX6
type B pancreatic cell differentiation	1	1053.2×	0.004	PAX6
forebrain dorsal/ventral pattern formation	1	1053.2×	0.004	PAX6
lacrimal gland development	1	1053.2×	0.004	PAX6
ventral spinal cord development	1	936.2×	0.004	PAX6
positive regulation of epithelial cell differentiation	1	936.2×	0.004	PAX6
iris morphogenesis	1	936.2×	0.004	PAX6
dorsal/ventral axis specification	1	766.0×	0.004	PAX6
spinal cord motor neuron cell fate specification	1	766.0×	0.004	PAX6
cornea development in camera-type eye	1	648.1×	0.005	PAX6
tRNA wobble uridine modification	1	601.9×	0.005	ELP4
negative regulation of neuroblast proliferation	1	601.9×	0.005	PAX6
embryonic camera-type eye morphogenesis	1	561.7×	0.005	PAX6
cell fate determination	1	468.1×	0.006	PAX6
eye photoreceptor cell development	1	421.3×	0.006	PAX6
neuron fate commitment	1	401.2×	0.006	PAX6
astrocyte differentiation	1	383.0×	0.006	PAX6
signal transduction involved in regulation of gene expression	1	351.1×	0.006	PAX6
sensory organ development	1	337.0×	0.006	PAX6
pituitary gland development	1	324.1×	0.006	PAX6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PAX6	0	0
ELP4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PAX6, ELP4

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)
PAX6	0	—
ELP4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.