Coloboma

Summary

Coloboma (MONDO:0001476) is a disease (an umbrella term covering 8 Mondo subtypes) caused by variants in BMPR1B and PDGFRA, with 37 cohort genes and 4 clinical trials.

At a glance

• Causal genes: BMPR1B (GenCC Strong), PDGFRA (GenCC Strong)
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 37
• ClinVar variants: 43
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coloboma
Mondo ID	MONDO:0001476
MeSH	D003103
Orphanet	194
DOID	DOID:12270
NCIT	C98877
SNOMED CT	93390002
UMLS	C0009363
MedGen	1046
Is cancer (heuristic)	no

Also known as: coloboma of macula · coloboma of the eye · congenital ocular coloboma · ocular coloboma

Data availability: 43 ClinVar variants · 6 GenCC gene-disease records.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › coloboma

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Subtypes (8): microphthalmia, isolated, with coloboma, coloboma, ocular, autosomal dominant, coloboma of macula, coloboma of optic nerve, coloboma, ocular, autosomal recessive, coloboma of eye lens, coloboma of eyelid, calloso-genital dysplasia

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

43 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 8 conflicting classifications of pathogenicity, 7 pathogenic, 7 likely pathogenic, 6 pathogenic/likely pathogenic, 3 likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
68468	NM_000104.4(CYP1B1):c.868dup (p.Arg290fs)	CYP1B1	Pathogenic	reviewed by expert panel
3474	NM_001368894.2(PAX6):c.1310A>T (p.Ter437Leu)	ELP4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189359	NM_004214.5(FIBP):c.652C>T (p.Gln218Ter)	FIBP	Pathogenic/Likely pathogenic	no assertion criteria provided
625873	NM_001256012.3(MYH10):c.4505G>C (p.Arg1502Pro)	MYH10	Pathogenic	criteria provided, single submitter
1710335	NM_000278.5(PAX2):c.389_390insTGCT (p.Ser131fs)	PAX2	Pathogenic	criteria provided, single submitter
279862	NM_001368894.2(PAX6):c.823C>T (p.Arg275Ter)	PAX6	Pathogenic	criteria provided, multiple submitters, no conflicts
1710328	NM_000965.5(RARB):c.1151-1G>C	RARB	Pathogenic	criteria provided, single submitter
4056086	NM_001297595.2(SIN3B):c.382-2A>G	SIN3B	Pathogenic	criteria provided, single submitter
1383	NM_153704.6(TMEM67):c.1843T>C (p.Cys615Arg)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
440948	NM_014023.4(WDR37):c.374C>T (p.Thr125Ile)	WDR37	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
633617	NM_014023.4(WDR37):c.356C>T (p.Ser119Phe)	WDR37	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
633618	NM_014023.4(WDR37):c.389C>T (p.Thr130Ile)	WDR37	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
120326	NM_001130145.3(YAP1):c.370C>T (p.Arg124Ter)	YAP1	Pathogenic	no assertion criteria provided
929503	NM_005632.2:c.2904+1_2905-45del	CAPN15	Likely pathogenic	criteria provided, single submitter
637955	NM_001378964.1(CDON):c.622C>T (p.Arg208Ter)	CDON	Likely pathogenic	no assertion criteria provided
3377022	NM_003468.4(FZD5):c.1146del (p.Asp382fs)	FZD5	Likely pathogenic	criteria provided, single submitter
694330	NM_003468.4(FZD5):c.1081_1082insGAA (p.His361delinsArgAsn)	FZD5	Likely pathogenic	criteria provided, single submitter
694331	NM_003468.4(FZD5):c.1181_1246del (p.Asn394_Gly415del)	FZD5	Likely pathogenic	criteria provided, single submitter
2430200	NM_006744.4(RBP4):c.358G>C (p.Asp120His)	RBP4	Likely pathogenic	criteria provided, single submitter
633616	NM_014023.4(WDR37):c.386C>G (p.Ser129Cys)	WDR37	Likely pathogenic	criteria provided, single submitter
2366452	NM_001005273.3(CHD3):c.2626C>T (p.Arg876Cys)	CHD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
694329	NM_003468.4(FZD5):c.820del (p.Leu274fs)	FZD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2873450	NM_006734.4(HIVEP2):c.6404G>C (p.Arg2135Thr)	HIVEP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3675875	NM_001009999.3(KDM1A):c.1157A>G (p.Asn386Ser)	KDM1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
430902	NM_006744.4(RBP4):c.394T>A (p.Tyr132Asn)	RBP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
68476	NM_213606.4(SLC16A12):c.472T>C (p.Ser158Pro)	SLC16A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2903254	NM_005862.3(STAG1):c.1744-5_1744-3del	STAG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
217725	NM_153704.6(TMEM67):c.1321C>T (p.Arg441Cys)	TMEM67	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
68471	NM_001195.5(BFSP1):c.776G>C (p.Cys259Ser)	BFSP1	Uncertain significance	no assertion criteria provided
1330213	GRCh37/hg19 10q25.3-26.12(chr10:118891670-122349064)x1	CACUL1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 52 · Orphanet: 81 · 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
BMPR1B	Strong	Autosomal dominant	coloboma	17
PDGFRA	Strong	Autosomal dominant	coloboma	8
ANK3	Moderate	Autosomal dominant	coloboma	7
BMP3	Moderate	Autosomal dominant	coloboma
MYH10	Limited	Autosomal dominant	coloboma	4
PRKRA	Limited	Autosomal recessive	coloboma	10
RAX	Limited	Autosomal recessive	coloboma	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMPR1B	Orphanet:2098	Acromesomelic dysplasia, Grebe type
BMPR1B	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
BMPR1B	Orphanet:93384	Brachydactyly type C
BMPR1B	Orphanet:93388	Brachydactyly type A1
BMPR1B	Orphanet:93396	Brachydactyly type A2
RAX	Orphanet:35612	Nanophthalmos
RAX	Orphanet:98938	Colobomatous microphthalmia
ANK3	Orphanet:356996	ANK3-related intellectual disability-sleep disturbance syndrome
PDGFRA	Orphanet:168940	Chronic eosinophilic leukemia
PDGFRA	Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRA	Orphanet:199306	Cleft lip/palate
PDGFRA	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRA	Orphanet:44890	Gastrointestinal stromal tumor
PDGFRA	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
PRKRA	Orphanet:210571	Dystonia 16
BFSP1	Orphanet:98991	Early-onset nuclear cataract
SMO	Orphanet:1553	Curry-Jones syndrome
SMO	Orphanet:2495	Meningioma
SMO	Orphanet:388	Hirschsprung disease
CAPN15	Orphanet:611201	Oculogastrointestinal-neurodevelopmental syndrome
STAG1	Orphanet:502434	STAG1-related intellectual disability-facial dysmorphism-gastroesophageal reflux syndrome
YAP1	Orphanet:1473	Uveal coloboma-cleft lip and palate-intellectual disability
YAP1	Orphanet:157791	Epithelioid hemangioendothelioma
CDON	Orphanet:220386	Semilobar holoprosencephaly
CDON	Orphanet:280195	Septopreoptic holoprosencephaly
CDON	Orphanet:280200	Microform holoprosencephaly
CDON	Orphanet:93924	Lobar holoprosencephaly
CDON	Orphanet:93925	Alobar holoprosencephaly
CDON	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
CDON	Orphanet:95496	Pituitary stalk interruption syndrome
AFF4	Orphanet:444077	Cognitive impairment-coarse facies-heart defects-obesity-pulmonary involvement-short stature-skeletal dysplasia syndrome
CDK5RAP2	Orphanet:2512	Autosomal recessive primary microcephaly
CHD3	Orphanet:599082	CHD3-related developmental delay-speech delay-intellectual disability-abnormalities of vision-facial dysmorphism syndrome
CHD4	Orphanet:653712	CHD4-related neurodevelopmental disorder
SIN3B	Orphanet:500166	SIN3-related intellectual disability syndrome due to a point mutation
CILK1	Orphanet:199332	Endocrine-cerebro-osteodysplasia syndrome
CILK1	Orphanet:307	Juvenile myoclonic epilepsy
SLC16A12	Orphanet:247794	Juvenile cataract-microcornea-renal glucosuria syndrome
CYP1B1	Orphanet:708	Peters anomaly
CYP1B1	Orphanet:98976	Congenital glaucoma
CYP1B1	Orphanet:98977	Juvenile glaucoma
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
NIPBL	Orphanet:199	Cornelia de Lange syndrome
NIPBL	Orphanet:329802	5p13 microduplication syndrome
KDM1A	Orphanet:189427	Cushing syndrome due to bilateral macronodular adrenocortical disease
KDM1A	Orphanet:477993	Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome

Cohort genes → proteins

37 cohort genes, 37 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	37

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYH10	HGNC:7568	ENSG00000133026	P35580	Myosin-10	gencc,clinvar
BMP3	HGNC:1070	ENSG00000152785	P12645	Bone morphogenetic protein 3	gencc
BMPR1B	HGNC:1077	ENSG00000138696	O00238	Bone morphogenetic protein receptor type-1B	gencc
RAX	HGNC:18662	ENSG00000134438	Q9Y2V3	Retinal homeobox protein Rx	gencc
ANK3	HGNC:494	ENSG00000151150	Q12955	Ankyrin-3	gencc
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	gencc
PRKRA	HGNC:9438	ENSG00000180228	O75569	Interferon-inducible double-stranded RNA-dependent protein kinase activator A	gencc
BFSP1	HGNC:1040	ENSG00000125864	Q12934	Filensin	clinvar
SMO	HGNC:11119	ENSG00000128602	Q99835	Protein smoothened	clinvar
CAPN15	HGNC:11182	ENSG00000103326	O75808	Calpain-15	clinvar
STAG1	HGNC:11354	ENSG00000118007	Q8WVM7	Cohesin subunit SA-1	clinvar
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	clinvar
PMEPA1	HGNC:14107	ENSG00000124225	Q969W9	Protein TMEPAI	clinvar
SMOX	HGNC:15862	ENSG00000088826	Q9NWM0	Spermine oxidase	clinvar
YAP1	HGNC:16262	ENSG00000137693	P46937	Transcriptional coactivator YAP1	clinvar
CDON	HGNC:17104	ENSG00000064309	Q4KMG0	Cell adhesion molecule-related/down-regulated by oncogenes	clinvar
AFF4	HGNC:17869	ENSG00000072364	Q9UHB7	AF4/FMR2 family member 4	clinvar
CDK5RAP2	HGNC:18672	ENSG00000136861	Q96SN8	CDK5 regulatory subunit-associated protein 2	clinvar
CHD3	HGNC:1918	ENSG00000170004	Q12873	ATP-dependent chromatin remodeler CHD3	clinvar
CHD4	HGNC:1919	ENSG00000111642	Q14839	ATP-dependent chromatin remodeler CHD4	clinvar
SIN3B	HGNC:19354	ENSG00000127511	O75182	Paired amphipathic helix protein Sin3b	clinvar
CILK1	HGNC:21219	ENSG00000112144	Q9UPZ9	Serine/threonine-protein kinase ICK	clinvar
SLC16A12	HGNC:23094	ENSG00000152779	Q6ZSM3	Monocarboxylate transporter 12	clinvar
CACUL1	HGNC:23727	ENSG00000151893	Q86Y37	CDK2-associated and cullin domain-containing protein 1	clinvar
CYP1B1	HGNC:2597	ENSG00000138061	Q16678	Cytochrome P450 1B1	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
KDM1A	HGNC:29079	ENSG00000004487	O60341	Lysine-specific histone demethylase 1A	clinvar
WDR37	HGNC:31406	ENSG00000047056	Q9Y2I8	WD repeat-containing protein 37	clinvar
FIBP	HGNC:3705	ENSG00000172500	O43427	Acidic fibroblast growth factor intracellular-binding protein	clinvar
FZD5	HGNC:4043	ENSG00000163251	Q13467	Frizzled-5	clinvar
HIVEP2	HGNC:4921	ENSG00000010818	P31629	Transcription factor HIVEP2	clinvar
NHS	HGNC:7820	ENSG00000188158	Q6T4R5	Actin remodeling regulator NHS	clinvar
PAX2	HGNC:8616	ENSG00000075891	Q02962	Paired box protein Pax-2	clinvar
PAX6	HGNC:8620	ENSG00000007372	P26367	Paired box protein Pax-6	clinvar
RARB	HGNC:9865	ENSG00000077092	P10826	Retinoic acid receptor beta	clinvar
RBP4	HGNC:9922	ENSG00000138207	P02753	Retinol-binding protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH10	Myosin-10	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
BMP3	Bone morphogenetic protein 3	Growth factor of the TGF-beta superfamily that plays an essential role in developmental process by inducing and patterning early skeletal formation and by negatively regulating bone density.
BMPR1B	Bone morphogenetic protein receptor type-1B	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
RAX	Retinal homeobox protein Rx	Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation.
ANK3	Ankyrin-3	Membrane-cytoskeleton linker.
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
PRKRA	Interferon-inducible double-stranded RNA-dependent protein kinase activator A	Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis.
BFSP1	Filensin	Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA.
SMO	Protein smoothened	G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling.
STAG1	Cohesin subunit SA-1	Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication.
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).
PMEPA1	Protein TMEPAI	Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression.
SMOX	Spermine oxidase	Flavoenzyme which catalyzes the oxidation of spermine to spermidine.
YAP1	Transcriptional coactivator YAP1	Transcriptional regulator with dual roles as a coactivator and corepressor.
CDON	Cell adhesion molecule-related/down-regulated by oncogenes	Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells.
AFF4	AF4/FMR2 family member 4	Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.
CDK5RAP2	CDK5 regulatory subunit-associated protein 2	Potential regulator of CDK5 activity via its interaction with CDK5R1.
CHD3	ATP-dependent chromatin remodeler CHD3	ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA.
CHD4	ATP-dependent chromatin remodeler CHD4	ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA.
SIN3B	Paired amphipathic helix protein Sin3b	Acts as a transcriptional repressor.
CILK1	Serine/threonine-protein kinase ICK	Required for ciliogenesis.
SLC16A12	Monocarboxylate transporter 12	Functions as a transporter for creatine and as well for its precursor guanidinoacetate.
CACUL1	CDK2-associated and cullin domain-containing protein 1	Cell cycle associated protein capable of promoting cell proliferation through the activation of CDK2 at the G1/S phase transition.
CYP1B1	Cytochrome P450 1B1	A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins.
TMEM67	Meckelin	Required for ciliary structure and function.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
KDM1A	Lysine-specific histone demethylase 1A	Histone demethylase that can demethylate both ‘Lys-4’ (H3K4me) and ‘Lys-9’ (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context.
WDR37	WD repeat-containing protein 37	Required for normal ER Ca2+ handling in lymphocytes.
FIBP	Acidic fibroblast growth factor intracellular-binding protein	May be involved in mitogenic function of FGF1.
FZD5	Frizzled-5	Receptor for Wnt proteins.
HIVEP2	Transcription factor HIVEP2	This protein specifically binds to the DNA sequence 5’-GGGACTTTCC-3’ which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1.
NHS	Actin remodeling regulator NHS	May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation.
PAX2	Paired box protein Pax-2	Transcription factor that may have a role in kidney cell differentiation.
PAX6	Paired box protein Pax-6	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas.
RARB	Retinoic acid receptor beta	Receptor for retinoic acid.
RBP4	Retinol-binding protein 4	Retinol-binding protein that mediates retinol transport in blood plasma.

Protein-family classification

Druggable: 10 · Difficult: 11 · Unknown: 16 · Druggable fraction: 0.27

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
Nuclear receptor	1	10.4×	0.409
Kinase	3	2.2×	0.409
Scaffold/PPI	4	1.9×	0.409
Transcription factor	7	1.6×	0.409
Transporter	1	2.1×	0.761
GPCR	2	1.3×	0.769
Protease	1	1.0×	0.906
Antibody/Immunoglobulin	1	0.8×	0.906
Other/Unknown	16	0.8×	0.960
Enzyme (other)	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYH10	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
BMP3	Other/Unknown	no		TGF-b_C, TGF-beta-like, BMP3/BMP3B
BMPR1B	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
RAX	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
ANK3	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
PRKRA	Other/Unknown	no		dsRBD_dom, PRKRA_DSRM_1, PRKRA_DSRM_2
BFSP1	Other/Unknown	no		IF_rod_dom, BFSP1
SMO	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
CAPN15	Protease	yes	3.4.22.B35	Pept_cys_AS, Peptidase_C2_calpain_cat, Znf_RanBP2
STAG1	Other/Unknown	no		STAG, ARM-type_fold, SCD
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
PMEPA1	Other/Unknown	no		TMEPAI/LRAD4
SMOX	Enzyme (other)	yes	1.5.3.16	Amino_oxidase, FAD/NAD-bd_sf, Flavin_monoamine_oxidase
YAP1	Scaffold/PPI	no		WW_dom, WW_dom_sf, YAP1
CDON	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
AFF4	Other/Unknown	no		AF4/FMR2, AF4_int, AF4/FMR2_CHD
CDK5RAP2	Other/Unknown	no		Cnn_1N, CDK5RAP2, CDK5RAP2_MYOME_CC
CHD3	Transcription factor	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
CHD4	Transcription factor	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
SIN3B	Other/Unknown	no		PAH, HDAC_interact_dom, Sin3_C
CILK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SLC16A12	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
CACUL1	Other/Unknown	no		Cullin_N, Cullin_repeat-like_dom_sf, CACUL1
CYP1B1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
KDM1A	Transcription factor	no	1.14.11.65	Amino_oxidase, SWIRM, Homeodomain-like_sf
WDR37	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
FIBP	Other/Unknown	no		FIBP
FZD5	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
HIVEP2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf,
NHS	Other/Unknown	no		NHS-like
PAX2	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf
RARB	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RBP4	Other/Unknown	no		Lipocln_cytosolic_FA-bd_dom, Retinol-bd/Purpurin, Calycin

Expression context

Cohort genes with no expression data: 0.

36 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)	37
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	7
calcaneal tendon	6
ganglionic eminence	4
male germ line stem cell (sensu Vertebrata) in testis	3
cortical plate	3
right uterine tube	3
palpebral conjunctiva	3
buccal mucosa cell	3
right coronary artery	2
saphenous vein	2
cauda epididymis	2
biceps brachii	2
parotid gland	2
endothelial cell	2
synovial joint	2
tibia	2
sperm	2
primordial germ cell in gonad	2
tendon of biceps brachii	2
right ovary	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH10	300	ubiquitous	marker	blood vessel layer, saphenous vein, right coronary artery
BMP3	126	tissue_specific	marker	muscle layer of sigmoid colon, male germ line stem cell (sensu Vertebrata) in testis, rectum
BMPR1B	239	broad	marker	calcaneal tendon, bronchial epithelial cell, cauda epididymis
RAX	29	tissue_specific	marker	parotid gland, nasal cavity epithelium, biceps brachii
ANK3	298	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, dorsal motor nucleus of vagus nerve
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint
PRKRA	294	ubiquitous	marker	sperm, skeletal muscle tissue of biceps brachii, biceps brachii
BFSP1	176	broad	yes	tendon of biceps brachii, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
SMO	225	ubiquitous	marker	ventricular zone, left ovary, right ovary
CAPN15	235	ubiquitous	marker	lower esophagus mucosa, granulocyte, mucosa of transverse colon
STAG1	293	ubiquitous	marker	calcaneal tendon, parotid gland, sural nerve
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad
PMEPA1	277	ubiquitous	marker	visceral pleura, ascending aorta, thoracic aorta
SMOX	258	ubiquitous	marker	amygdala, lower esophagus mucosa, C1 segment of cervical spinal cord
YAP1	279	ubiquitous	marker	saphenous vein, germinal epithelium of ovary, cauda epididymis
CDON	222	ubiquitous	marker	ventricular zone, ganglionic eminence, calcaneal tendon
AFF4	271	ubiquitous	marker	esophagus squamous epithelium, germinal epithelium of ovary, sperm
CDK5RAP2	272	ubiquitous	marker	sural nerve, ventricular zone, right coronary artery
CHD3	263	ubiquitous	marker	cortical plate, ganglionic eminence, right uterine tube
CHD4	284	ubiquitous	marker	ventricular zone, ganglionic eminence, colonic epithelium
SIN3B	261	ubiquitous	marker	body of uterus, right uterine tube, right ovary
CILK1	268	ubiquitous	marker	adrenal tissue, palpebral conjunctiva, cortical plate
SLC16A12	119	broad	marker	body of pancreas, adult mammalian kidney, pancreas
CACUL1	254	ubiquitous	marker	upper arm skin, epithelium of nasopharynx, kidney epithelium
CYP1B1	285	ubiquitous	marker	pericardium, cartilage tissue, synovial joint
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
KDM1A	287	ubiquitous	marker	ganglionic eminence, ventricular zone, cortical plate
WDR37	279	ubiquitous	marker	secondary oocyte, tibia, middle temporal gyrus
FIBP	290	ubiquitous	marker	stromal cell of endometrium, right frontal lobe, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
YAP1	6,742
CHD4	6,397
KDM1A	6,235
ANK3	6,145
CHD3	5,202
PDGFRA	5,186
PAX6	4,971
MYH10	3,368
NIPBL	3,278
CYP1B1	2,883

Intra-cohort edges

A	B	Sources
ANK3	YAP1	intact
BMP3	KDM1A	biogrid_interaction, intact
CACUL1	KDM1A	intact
CDON	SMO	string_interaction
CHD3	CHD4	string_interaction
CHD3	KDM1A	string_interaction
CHD4	KDM1A	string_interaction
ELP4	PAX6	string_interaction
NIPBL	STAG1	string_interaction

Structural data

PDB: 23 · AlphaFold-only: 14 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KDM1A	O60341	128
YAP1	P46937	41
RBP4	P02753	23
STAG1	Q8WVM7	20
PDGFRA	P16234	15
SMO	Q99835	15
CHD4	Q14839	12
AFF4	Q9UHB7	9
RARB	P10826	9
CDK5RAP2	Q96SN8	4
SIN3B	O75182	4
FZD5	Q13467	4
CDON	Q4KMG0	3
NIPBL	Q6KC79	3
PRKRA	O75569	2
SMOX	Q9NWM0	2
CYP1B1	Q16678	2
PAX6	P26367	2
MYH10	P35580	1
BMP3	P12645	1
BMPR1B	O00238	1
ANK3	Q12955	1
TMEM67	Q5HYA8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FIBP	O43427	92.33
SLC16A12	Q6ZSM3	80.04
WDR37	Q9Y2I8	78.86
ELP4	Q96EB1	74.49
CACUL1	Q86Y37	74.25
CAPN15	O75808	71.65
RAX	Q9Y2V3	65.10
BFSP1	Q12934	64.66
CHD3	Q12873	63.21
PAX2	Q02962	61.52
CILK1	Q9UPZ9	61.47
PMEPA1	Q969W9	57.03
NHS	Q6T4R5	43.65
HIVEP2	P31629	36.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 176. Enrichment computed across 37 evidence-associated genes (28 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 28 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP1B1 causes Glaucoma	1	407.9×	0.031	CYP1B1
Retinoid metabolism disease events	1	407.9×	0.031	RBP4
Imatinib-resistant PDGFR mutants	1	407.9×	0.031	PDGFRA
Sunitinib-resistant PDGFR mutants	1	407.9×	0.031	PDGFRA
Regorafenib-resistant PDGFR mutants	1	407.9×	0.031	PDGFRA
Sorafenib-resistant PDGFR mutants	1	407.9×	0.031	PDGFRA
PDGFR mutants bind TKIs	1	407.9×	0.031	PDGFRA
Cohesin Loading onto Chromatin	2	81.6×	0.031	STAG1, NIPBL
Activation of SMO	2	45.3×	0.031	SMO, CDON
Regulation of TP53 Activity through Acetylation	2	32.6×	0.031	CHD3, CHD4
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	2	27.2×	0.031	CHD3, CHD4
Regulation of PTEN gene transcription	3	19.1×	0.031	CHD3, CHD4, KDM1A
HDACs deacetylate histones	3	12.9×	0.031	CHD3, CHD4, KDM1A
Potential therapeutics for SARS	3	12.2×	0.031	CHD3, CHD4, KDM1A
RHO GTPases activate PKNs	2	22.7×	0.041	MYH10, KDM1A
PAOs oxidise polyamines to amines	1	135.9×	0.072	SMOX
Defective visual phototransduction due to STRA6 loss of function	1	135.9×	0.072	RBP4
RNA Polymerase I Transcription Initiation	2	16.0×	0.072	CHD3, CHD4
Interconversion of polyamines	1	102.0×	0.084	SMOX
Class B/2 (Secretin family receptors)	2	13.6×	0.084	SMO, FZD5
Signaling by Hedgehog	2	13.2×	0.084	SMO, CDON
Hedgehog ‘on’ state	2	11.3×	0.107	SMO, CDON
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	2	10.9×	0.110	CHD3, CHD4
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	51.0×	0.112	CYP1B1
Ligand-receptor interactions	1	51.0×	0.112	CDON
Mitotic Telophase/Cytokinesis	1	51.0×	0.112	STAG1
RUNX3 regulates YAP1-mediated transcription	1	51.0×	0.112	YAP1
Formation of intermediate mesoderm	1	51.0×	0.112	PAX2
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	2	10.5×	0.112	CHD3, CHD4
NuRD complex assembly	2	10.1×	0.112	CHD3, CHD4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 37 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of neuroblast proliferation	4	62.8×	2e-04	SMO, CDON, KDM1A, PAX6
eye development	4	38.0×	7e-04	BMPR1B, FZD5, PAX6, RBP4
positive regulation of transcription by RNA polymerase II	12	4.8×	7e-04	BMP3, BMPR1B, SMO, YAP1, CDON, RAX, NIPBL, KDM1A (+4 more)
central nervous system neuron differentiation	3	48.8×	0.004	BMPR1B, SMO, CDON
regulation of metanephric nephron tubule epithelial cell differentiation	2	182.2×	0.005	YAP1, PAX2
establishment of mitotic sister chromatid cohesion	2	130.1×	0.008	STAG1, NIPBL
embryonic retina morphogenesis in camera-type eye	2	130.1×	0.008	CDON, RBP4
lens development in camera-type eye	3	30.4×	0.008	CDON, NHS, PAX6
neuroblast proliferation	3	29.7×	0.008	SMO, CDON, PAX6
negative regulation of transcription by RNA polymerase II	9	4.3×	0.009	SMO, YAP1, CHD3, CHD4, SIN3B, NIPBL, KDM1A, PAX6 (+1 more)
regulation of cell fate specification	2	70.1×	0.016	CHD3, CHD4
cardiac myofibril assembly	2	70.1×	0.016	MYH10, PDGFRA
negative regulation of epithelial cell differentiation	2	65.1×	0.016	SMO, YAP1
retina development in camera-type eye	3	20.7×	0.016	MYH10, BMPR1B, PAX6
embryonic camera-type eye morphogenesis	2	60.7×	0.017	FZD5, PAX6
positive regulation of epithelial cell proliferation	3	19.8×	0.017	SMO, YAP1, PAX2
cell fate determination	2	50.6×	0.020	PAX2, PAX6
retinal metabolic process	2	50.6×	0.020	CYP1B1, RBP4
embryonic digestive tract morphogenesis	2	50.6×	0.020	NIPBL, PDGFRA
cerebral cortex development	3	16.7×	0.021	SMO, CDON, KDM1A
regulation of stem cell differentiation	2	41.4×	0.027	CHD3, CHD4
smoothened signaling pathway	3	14.7×	0.027	SMO, CDON, PAX6
pancreatic A cell development	1	455.5×	0.029	PAX6
ventral midline determination	1	455.5×	0.029	SMO
oligodendrocyte cell fate specification	1	455.5×	0.029	PAX6
forebrain-midbrain boundary formation	1	455.5×	0.029	PAX6
somatic motor neuron fate commitment	1	455.5×	0.029	PAX6
external genitalia morphogenesis	1	455.5×	0.029	NIPBL
benzene-containing compound metabolic process	1	455.5×	0.029	CYP1B1
optic chiasma development	1	455.5×	0.029	PAX2

Therapeutics

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 10 · Phased (≥1): 11 · Undrugged: 26

Druggability breadth: 18 of 37 evidence-associated genes (49%) 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
MYH10	QUIZARTINIB
BMPR1B	MOMELOTINIB
PDGFRA	PONATINIB
SMO	INFIGRATINIB
CILK1	MOMELOTINIB
CYP1B1	PAZOPANIB
KDM1A	OSIMERTINIB
RARB	BEXAROTENE
RBP4	RETINOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRA	77	4
KDM1A	38	4
BMPR1B	28	4
CILK1	24	4
CYP1B1	22	4
RARB	18	4
SMO	11	4
RBP4	3	4
MYH10	2	4
CHD4	2	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
QUIZARTINIB	4	BMPR1B, MYH10, PDGFRA
MOMELOTINIB	4	BMPR1B, CILK1
FEDRATINIB	4	BMPR1B, CILK1, PDGFRA
AXITINIB	4	BMPR1B, PDGFRA
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B, PDGFRA
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B, CYP1B1, PDGFRA
SUNITINIB	4	BMPR1B, CILK1, PDGFRA
DASATINIB	4	BMPR1B, PDGFRA
CRIZOTINIB	4	BMPR1B
PONATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA, SMO
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
NINTEDANIB	4	CILK1, PDGFRA
ERLOTINIB	4	KDM1A, PDGFRA
MIDOSTAURIN	4	CILK1, PDGFRA
IMATINIB	4	PDGFRA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
KDM1A	1,089	Binding:1075, Functional:7, ADMET:7
CYP1B1	408	ADMET:281, Binding:127
RARB	278	Binding:199, Functional:78, ADMET:1
BMPR1B	166	Binding:164, ADMET:2
YAP1	135	Binding:135
SMO	131	Binding:111, Functional:20
CILK1	119	Binding:119
RBP4	32	Binding:29, Functional:3
SMOX	18	Binding:15, ADMET:3
CHD4	10	Binding:9, Functional:1
AFF4	9	Binding:9
FZD5	8	Functional:6, Binding:2
MYH10	3	Binding:3
CHD3	1	Binding:1
FIBP	1	Binding:1
HIVEP2	1	Binding:1
PAX2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMPR1B	2.7.10.2	non-specific protein-tyrosine kinase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
CAPN15	3.4.22.B35
SMOX	1.5.3.16	spermine oxidase
KDM1A	1.14.11.65, 1.14.11.66, 1.14.11.67, 1.14.99.66	[histone H3]-dimethyl-L-lysine9 demethylase, [histone H3]-trimethyl-L-lysine9 demethylase, [histone H3]-trimethyl-L-lysine4 demethylase, [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BMPR1B	166
PDGFRA	1,172
SMO	131
YAP1	135
CILK1	119
CYP1B1	408
KDM1A	1,089
RARB	278

Pharmacogenomics

Cohort genes with a PharmGKB record: 37; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
QUIZARTINIB	4	BMPR1B, MYH10, PDGFRA
MOMELOTINIB	4	BMPR1B, CILK1
FEDRATINIB	4	BMPR1B, CILK1, PDGFRA
AXITINIB	4	BMPR1B, PDGFRA
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B, PDGFRA
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B, CYP1B1, PDGFRA
SUNITINIB	4	BMPR1B, CILK1, PDGFRA
DASATINIB	4	BMPR1B, PDGFRA
CRIZOTINIB	4	BMPR1B
PONATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA, SMO
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
NINTEDANIB	4	CILK1, PDGFRA
ERLOTINIB	4	KDM1A, PDGFRA
MIDOSTAURIN	4	CILK1, PDGFRA
IMATINIB	4	PDGFRA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	9	MYH10, BMPR1B, PDGFRA, SMO, CILK1, CYP1B1, KDM1A, RARB, RBP4
B	Phased (≥1) drug, not yet approved	2	AFF4, CHD4
C	Druggable family + PDB, no drug	3	SMOX, CDON, FZD5
D	Druggable family + AlphaFold only, no drug	2	CAPN15, SLC16A12
E	Difficult family or no structure, no drug	21	BMP3, RAX, ANK3, PRKRA, BFSP1, STAG1, ELP4, PMEPA1, YAP1, CDK5RAP2 (+11 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
YAP1	135	—
BMP3	0	—
RAX	0	—
ANK3	0	—
PRKRA	0	—
BFSP1	0	—
CAPN15	0	—
STAG1	0	—
ELP4	0	—
PMEPA1	0	—
SMOX	18	—
CDON	0	—
CDK5RAP2	0	—
CHD3	1	—
SIN3B	0	—
SLC16A12	0	—
CACUL1	0	—
TMEM67	0	—
NIPBL	0	—
WDR37	0	—
FIBP	1	—
FZD5	8	—
HIVEP2	1	—
NHS	0	—
PAX2	1	—
PAX6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01778543	Not specified	RECRUITING	Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)
NCT06293560	Not specified	RECRUITING	Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children
NCT00368004	Not specified	TERMINATED	Family Studies of Uveal Coloboma
NCT04833361	Not specified	COMPLETED	Potential Environmental Causes of Uveal Coloboma