Glaucoma

Summary

Glaucoma (MONDO:0005041) is a disease (an umbrella term covering 11 Mondo subtypes) with 75 cohort genes (860 GWAS associations across 74 studies) and 1,034 clinical trials. The dominant Reactome pathway is Regulation of Complement cascade (6 cohort genes). Top therapeutic interventions include timolol, brimonidine, and latanoprost.

At a glance

• Umbrella term: 11 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 860
• ClinVar variants: 52
• Clinical trials: 1,034

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glaucoma
Mondo ID	MONDO:0005041
MeSH	D005901
DOID	DOID:1686
ICD-10-CM	H40, H40-H42
ICD-11	499924848
NCIT	C26782
SNOMED CT	23986001
UMLS	C0017601
MedGen	42224
Is cancer (heuristic)	no

Also known as: glaucoma · glaucoma (disease)

Data availability: 52 ClinVar variants · 860 GWAS associations (74 studies) · 3 GenCC gene-disease records · 1 HPO phenotype · 3 cell lines.

Disease family

An umbrella term covering 11 Mondo subtypes.

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

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, 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, 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 (11): glaucomatous atrophy of optic disk, hypersecretion glaucoma, aqueous misdirection, phacogenic glaucoma, traumatic glaucoma, angle-closure glaucoma, borderline glaucoma, steroid-induced glaucoma, open-angle glaucoma, hereditary glaucoma, secondary early-onset glaucoma

Genetics & variants

GWAS landscape

860 GWAS associations across 74 studies. Top hits map to 13 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs7030641	3e-140	CDKN2B-AS1	C	0.13
rs6475604	1e-107	CDKN2B-AS1	T	0.14
rs10918274	6e-92	TMCO1	T	1.37
rs4822983	7e-90	CHEK2	C	0.12
chr22:29101357	2e-88		A	0.11
chr12:83996127	4e-86		C	0.1
chr1:165705788	6e-84		C	0.15
rs34935520	3e-80	C14orf39 - SALRNA1	G	0.1
rs7961422	1e-72	RPL6P25 - SLC6A15	G	0.1
rs12133745	1e-71	TMCO1	C	0.15
rs1192415	3e-67	WDR82P2 - HSP90B3P	G	0.11
chr1:165774286	1e-65		G	0.26
rs3858145	3e-60	LINC02640 - KRT19P4	A	0.09
rs2472493	8e-59	ABCA1 - CT70	G	1.19
rs9913911	1e-58	GAS7	A	1.19
chr10:70011354	4e-58		C	0.09
rs12150284	1e-57	GAS7	C	0.09
rs33912345	1e-56	C14orf39, SIX6	C	0.09
chr9:104933258	5e-55		C	0.16
rs7518099	2e-52	TMCO1	T	1.37
chr20:6470094	2e-52		G	0.08
chr1:171636338	1e-50		A	1.46
chr9:22052735	2e-50		C	0.16
chr9:107695539	2e-49		T	0.08
rs59454355	4e-49	CAV2 - CAV1	G	1.19
rs4657476	3e-47	TMCO1	C	0.25
chr17:10127866	2e-46		G	0.16
chr1:165687761	2e-44		A	0.25
rs28464089	2e-43	AFAP1	C	0.07
rs4657477	4e-43	TMCO1	C	0.22

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90271893	Yao X	2023	14,034	784,851	Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders.
GCST90271895	Yao X	2023	14,034	434,963	Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders.
GCST90271894	Yao X	2023	11,306	693,697	Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders.
GCST006395	MacGregor S	2018	11,018	126,068	Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma.
GCST90018852	Sakaue S	2021	10,411	474,568	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90018632	Sakaue S	2021	8,448	168,903	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90079909	Backman JD	2021	8,122	376,438	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083895	Backman JD	2021	8,122	376,438	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST009722	Craig JE	2020	7,947	119,318	Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.
GCST009726	Craig JE	2020	7,947	119,318	Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	1
Tier 3: regulatory	2
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	40
low_freq (0.01-0.05)	1
rare (<0.01)	2
unknown	7

Functional consequences

Consequence	Count
intron_variant	23
unknown	17
intergenic_variant	4
regulatory_region_variant	2
missense_variant	1
non_coding_transcript_exon_variant	1
stop_gained	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs7030641	9	22054041	C>T	0.427	intron_variant	CDKN2B-AS1	3e-140	Tier 4: intronic/intergenic
rs6475604	9	22052735	T>A,C,G	0.338	intron_variant	CDKN2B-AS1	1e-107	Tier 4: intronic/intergenic
rs10918274	1	165745179	T>A,C,G	0.12	intron_variant	TMCO1	6e-92	Tier 4: intronic/intergenic
rs4822983	22	28719078	C>T	0.314	intron_variant	CHEK2	7e-90	Tier 4: intronic/intergenic
chr22:29101357				0.32			2e-88	Tier 4: intronic/intergenic
chr12:83996127				0.48			4e-86	Tier 4: intronic/intergenic
chr1:165705788				0.141			6e-84	Tier 4: intronic/intergenic
rs34935520	14	60624683	G>A	0.405	intron_variant	C14orf39 - SALRNA1	3e-80	Tier 4: intronic/intergenic
rs7961422	12	83672001	G>C,T	0.4	intergenic_variant	RPL6P25 - SLC6A15	1e-72	Tier 4: intronic/intergenic
rs12133745	1	165745445	C>A,G,T	0.13	intron_variant	TMCO1	1e-71	Tier 4: intronic/intergenic
rs1192415	1	91611540	G>A,C,T	0.183	regulatory_region_variant	WDR82P2 - HSP90B3P	3e-67	Tier 3: regulatory
chr1:165774286							1e-65	Tier 4: intronic/intergenic
rs3858145	10	68252081	A>G	0.308	intergenic_variant	LINC02640 - KRT19P4	3e-60	Tier 4: intronic/intergenic
rs2472493	9	104933567	G>A,C,T	0.45	intron_variant	ABCA1 - CT70	8e-59	Tier 4: intronic/intergenic
rs9913911	17	10127866	A>G	0.38	intron_variant	GAS7	1e-58	Tier 4: intronic/intergenic
chr10:70011354				0.276			4e-58	Tier 4: intronic/intergenic
rs12150284	17	10127773	C>A,G,T	0.362	intron_variant	GAS7	1e-57	Tier 4: intronic/intergenic
rs33912345	14	60509819	C>A,G	0.499	missense_variant	C14orf39, SIX6	1e-56	Tier 1: coding
chr9:104933258							5e-55	Tier 4: intronic/intergenic
rs7518099	1	165767643	C>T	0.05	intron_variant	TMCO1	2e-52	Tier 4: intronic/intergenic
chr20:6470094				0.359			2e-52	Tier 4: intronic/intergenic
chr1:171636338							1e-50	Tier 4: intronic/intergenic
chr9:22052735							2e-50	Tier 4: intronic/intergenic
chr9:107695539				0.431			2e-49	Tier 4: intronic/intergenic
rs59454355	7	116515969	C>A,G,T	0.27	intergenic_variant	CAV2 - CAV1	4e-49	Tier 4: intronic/intergenic
rs4657476	1	165763424	C>A,T	0.131	intron_variant	TMCO1	3e-47	Tier 4: intronic/intergenic
chr17:10127866							2e-46	Tier 4: intronic/intergenic
chr1:165687761				0.139			2e-44	Tier 4: intronic/intergenic
rs28464089	4	7888230	C>A	0.409	intron_variant	AFAP1	2e-43	Tier 4: intronic/intergenic
rs4657477	1	165766938	C>G,T	0.138	intron_variant	TMCO1	4e-43	Tier 4: intronic/intergenic

ClinVar germline variants

52 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 13 likely benign, 11 benign, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
374025	NM_004380.3(CREBBP):c.3698G>A (p.Arg1233Lys)	CREBBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374184	NM_001174096.2(ZEB1):c.976C>T (p.Arg326Ter)	ZEB1	Pathogenic	criteria provided, multiple submitters, no conflicts
267877	46;XX;t(X;22)(q13;q13)		Uncertain significance	criteria provided, single submitter
2431657	NM_015313.3(ARHGEF12):c.4449_4455del (p.Met1483fs)	ARHGEF12	Uncertain significance	criteria provided, single submitter
252960	NM_000261.2(MYOC):c.823A>T (p.Lys275Ter)	MYOC	Uncertain significance	reviewed by expert panel
293702	NM_000261.2(MYOC):c.*426C>T	MYOC	Uncertain significance	criteria provided, single submitter
293703	NM_000261.2(MYOC):c.*331A>G	MYOC	Uncertain significance	criteria provided, single submitter
293704	NM_000261.2(MYOC):c.*241A>G	MYOC	Uncertain significance	criteria provided, multiple submitters, no conflicts
293705	NM_000261.2(MYOC):c.*188C>T	MYOC	Uncertain significance	criteria provided, single submitter
293706	NM_000261.2(MYOC):c.*182C>A	MYOC	Uncertain significance	criteria provided, single submitter
293707	NM_000261.2(MYOC):c.*71G>A	MYOC	Uncertain significance	criteria provided, single submitter
293710	NM_000261.2(MYOC):c.992C>T (p.Ser331Leu)	MYOC	Uncertain significance	reviewed by expert panel
293712	NM_000261.2(MYOC):c.871G>A (p.Val291Ile)	MYOC	Uncertain significance	reviewed by expert panel
293713	NM_000261.2(MYOC):c.865G>A (p.Asp289Asn)	MYOC	Uncertain significance	reviewed by expert panel
293714	NM_000261.2(MYOC):c.728C>A (p.Thr243Asn)	MYOC	Uncertain significance	reviewed by expert panel
293716	NM_000261.2(MYOC):c.568G>T (p.Asp190Tyr)	MYOC	Uncertain significance	reviewed by expert panel
293719	NM_000261.2(MYOC):c.335A>G (p.Glu112Gly)	MYOC	Uncertain significance	reviewed by expert panel
293720	NM_000261.2(MYOC):c.304T>A (p.Leu102Met)	MYOC	Uncertain significance	reviewed by expert panel
293721	NM_000261.2(MYOC):c.239C>A (p.Thr80Asn)	MYOC	Uncertain significance	reviewed by expert panel
293722	NM_000261.2(MYOC):c.224A>G (p.Gln75Arg)	MYOC	Uncertain significance	reviewed by expert panel
874097	NM_000261.2(MYOC):c.*273G>A	MYOC	Uncertain significance	criteria provided, single submitter
875032	NM_000261.2(MYOC):c.1408C>T (p.Arg470Cys)	MYOC	Uncertain significance	reviewed by expert panel
875084	NM_000261.2(MYOC):c.652G>A (p.Glu218Lys)	MYOC	Uncertain significance	reviewed by expert panel
875954	NM_000261.2(MYOC):c.1272G>C (p.Gln424His)	MYOC	Uncertain significance	reviewed by expert panel
876022	NM_000261.2(MYOC):c.611C>T (p.Thr204Met)	MYOC	Uncertain significance	reviewed by expert panel
876999	NM_000261.2(MYOC):c.600A>G (p.Arg200=)	MYOC	Uncertain significance	reviewed by expert panel
877000	NM_000261.2(MYOC):c.573T>A (p.Thr191=)	MYOC	Uncertain significance	reviewed by expert panel
877041	NM_000261.2(MYOC):c.31T>C (p.Phe11Leu)	MYOC	Uncertain significance	reviewed by expert panel
193066	NM_000261.2(MYOC):c.227G>A (p.Arg76Lys)	MYOC	Benign	reviewed by expert panel
196241	NM_000261.2(MYOC):c.855G>T (p.Thr285=)	MYOC	Benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 84 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
ARHGEF12	ARHGEF12	GWAS
ANGPT1	ANGPT1	GWAS, GenCC, Orphanet

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
ANGPT1	Moderate	Autosomal dominant	glaucoma	3
GLIS1	Limited	Autosomal recessive	glaucoma
PRPF8	Limited	Autosomal dominant	glaucoma	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANGPT1	Orphanet:599418	Hereditary angioedema with normal C1Inh not related to F12 or PLG variant
PRPF8	Orphanet:528084	Non-specific syndromic intellectual disability
PRPF8	Orphanet:791	Retinitis pigmentosa
SEMA3C	Orphanet:388	Hirschsprung disease
SIX1	Orphanet:107	BOR syndrome
SIX1	Orphanet:52429	Branchiootic syndrome
SIX1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
SIX6	Orphanet:35612	Nanophthalmos
SIX6	Orphanet:435930	Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
SIX6	Orphanet:98938	Colobomatous microphthalmia
ZEB1	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98974	Fuchs endothelial corneal dystrophy
CAV1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
CAV1	Orphanet:220402	Limited cutaneous systemic sclerosis
CAV1	Orphanet:275777	Heritable pulmonary arterial hypertension
CAV1	Orphanet:696206	Congenital generalized lipodystrophy type 3
ANKH	Orphanet:1416	Familial calcium pyrophosphate deposition
ANKH	Orphanet:1522	Craniometaphyseal dysplasia
CHEK2	Orphanet:1331	Familial prostate cancer
CHEK2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
CHEK2	Orphanet:440437	Familial colorectal cancer Type X
CHEK2	Orphanet:524	Li-Fraumeni syndrome
CHEK2	Orphanet:668	Osteosarcoma
CFHR3	Orphanet:329931	C3 glomerulonephritis
TRIOBP	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
PLCE1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
CDH11	Orphanet:1299	Branchioskeletogenital syndrome
CDKN2B	Orphanet:618	Familial melanoma
CDKN2B	Orphanet:652	Multiple endocrine neoplasia type 1
TXNRD2	Orphanet:154	Familial isolated dilated cardiomyopathy
TXNRD2	Orphanet:361	Familial glucocorticoid deficiency
TMCO1	Orphanet:1394	Cerebrofaciothoracic dysplasia
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
ASPM	Orphanet:2512	Autosomal recessive primary microcephaly
BICC1	Orphanet:730	Autosomal dominant polycystic kidney disease
C14orf39	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
ANTXR1	Orphanet:2067	GAPO syndrome
ELOVL5	Orphanet:423296	Spinocerebellar ataxia type 38
POU6F2	Orphanet:654	Nephroblastoma
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome
COL11A1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A1	Orphanet:90654	Stickler syndrome type 2
PNPT1	Orphanet:101111	Spinocerebellar ataxia type 25

Cohort genes → proteins

75 cohort genes, 70 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	69
gwas_and_gencc	1
gwas_and_clinvar	1
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARHGEF12	HGNC:14193	ENSG00000196914	Q9NZN5	Rho guanine nucleotide exchange factor 12	gwas,clinvar
ANGPT1	HGNC:484	ENSG00000154188	Q15389	Angiopoietin-1	gwas,gencc
PRPF8	HGNC:17340	ENSG00000174231	Q6P2Q9	Pre-mRNA-processing-splicing factor 8	gencc
GLIS1	HGNC:29525	ENSG00000174332	Q8NBF1	Zinc finger protein GLIS1	gencc
SEMA3C	HGNC:10725	ENSG00000075223	Q99985	Semaphorin-3C	gwas
SEMA3F	HGNC:10728	ENSG00000001617	Q13275	Semaphorin-3F	gwas
SIX1	HGNC:10887	ENSG00000126778	Q15475	Homeobox protein SIX1	gwas
SIX6	HGNC:10892	ENSG00000184302	O95475	Homeobox protein SIX6	gwas
SUPT3H	HGNC:11466	ENSG00000196284	O75486	Transcription initiation protein SPT3 homolog	gwas
ZEB1	HGNC:11642	ENSG00000148516	P37275	Zinc finger E-box-binding homeobox 1	clinvar
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	gwas
PLEKHA1	HGNC:14335	ENSG00000107679	Q9HB21	Pleckstrin homology domain-containing family A member 1	gwas
TES	HGNC:14620	ENSG00000135269	Q9UGI8	Testin	gwas
CAV1	HGNC:1527	ENSG00000105974	Q03135	Caveolin-1	gwas
CAV2	HGNC:1528	ENSG00000105971	P51636	Caveolin-2	gwas
ANKH	HGNC:15492	ENSG00000154122	Q9HCJ1	Mineralization regulator ANKH	gwas
CTTNBP2	HGNC:15679	ENSG00000077063	Q8WZ74	Cortactin-binding protein 2	gwas
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	gwas
FBXO32	HGNC:16731	ENSG00000156804	Q969P5	F-box only protein 32	gwas
CFHR4	HGNC:16979	ENSG00000134365	Q92496	Complement factor H-related protein 4	gwas
CFHR3	HGNC:16980	ENSG00000116785	Q02985	Complement factor H-related protein 3	gwas
TRIOBP	HGNC:17009	ENSG00000100106	Q9H2D6	TRIO and F-actin-binding protein	gwas
PLCE1	HGNC:17175	ENSG00000138193	Q9P212	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	gwas
CDH11	HGNC:1750	ENSG00000140937	P55287	Cadherin-11	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
TXNRD2	HGNC:18155	ENSG00000184470	Q9NNW7	Thioredoxin reductase 2, mitochondrial	gwas
TMCO1	HGNC:18188	ENSG00000143183	Q9UM00	Calcium load-activated calcium channel	gwas
RBFOX1	HGNC:18222	ENSG00000078328	Q9NWB1	RNA binding protein fox-1 homolog 1	gwas
FMNL2	HGNC:18267	ENSG00000157827	Q96PY5	Formin-like protein 2	gwas
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	gwas
KCNT2	HGNC:18866	ENSG00000162687	Q6UVM3	Potassium channel subfamily T member 2	gwas
ASPM	HGNC:19048	ENSG00000066279	Q8IZT6	Abnormal spindle-like microcephaly-associated protein	gwas
BICC1	HGNC:19351	ENSG00000122870	Q9H694	Protein bicaudal C homolog 1	gwas
C14orf39	HGNC:19849	ENSG00000179008	Q8N1H7	Protein SIX6OS1	gwas
TMEM181	HGNC:20958	ENSG00000146433	Q9P2C4	Transmembrane protein 181	gwas
ANTXR1	HGNC:21014	ENSG00000169604	Q9H6X2	Anthrax toxin receptor 1	gwas
ELOVL5	HGNC:21308	ENSG00000012660	Q9NYP7	Very long chain fatty acid elongase 5	gwas
POU6F2	HGNC:21694	ENSG00000106536	P78424	POU domain, class 6, transcription factor 2	gwas
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	gwas
THSD7A	HGNC:22207	ENSG00000005108	Q9UPZ6	Thrombospondin type-1 domain-containing protein 7A	gwas
PNPT1	HGNC:23166	ENSG00000138035	Q8TCS8	Polyribonucleotide nucleotidyltransferase 1, mitochondrial	gwas
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
AFAP1	HGNC:24017	ENSG00000196526	Q8N556	Actin filament-associated protein 1	gwas
CFHR5	HGNC:24668	ENSG00000134389	Q9BXR6	Complement factor H-related protein 5	gwas
ZBTB41	HGNC:24819	ENSG00000177888	Q5SVQ8	Zinc finger and BTB domain-containing protein 41	gwas
EXOC2	HGNC:24968	ENSG00000112685	Q96KP1	Exocyst complex component 2	gwas
SRBD1	HGNC:25521	ENSG00000068784	Q8N5C6	S1 RNA-binding domain-containing protein 1	gwas
PTCD2	HGNC:25734	ENSG00000049883	Q8WV60	Pentatricopeptide repeat-containing protein 2, mitochondrial	gwas
DNAJC24	HGNC:26979	ENSG00000170946	Q6P3W2	DnaJ homolog subfamily C member 24	gwas
PLEKHA7	HGNC:27049	ENSG00000166689	Q6IQ23	Pleckstrin homology domain-containing family A member 7	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARHGEF12	Rho guanine nucleotide exchange factor 12	Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.
ANGPT1	Angiopoietin-1	Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation.
PRPF8	Pre-mRNA-processing-splicing factor 8	Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome.
GLIS1	Zinc finger protein GLIS1	Acts both as a repressor and an activator of transcription.
SEMA3C	Semaphorin-3C	Binds to plexin family members and plays an important role in the regulation of developmental processes.
SEMA3F	Semaphorin-3F	May play a role in cell motility and cell adhesion.
SIX1	Homeobox protein SIX1	Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development.
SIX6	Homeobox protein SIX6	May be involved in eye development.
SUPT3H	Transcription initiation protein SPT3 homolog	Probable transcriptional activator.
ZEB1	Zinc finger E-box-binding homeobox 1	Acts as a transcriptional repressor.
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).
PLEKHA1	Pleckstrin homology domain-containing family A member 1	Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides.
TES	Testin	Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton.
CAV1	Caveolin-1	May act as a scaffolding protein within caveolar membranes.
CAV2	Caveolin-2	May act as a scaffolding protein within caveolar membranes.
ANKH	Mineralization regulator ANKH	Transports adenosine triphosphate (ATP) and possibly other nucleoside triphosphates (NTPs) from cytosol to the extracellular space.
CTTNBP2	Cortactin-binding protein 2	Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance.
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
FBXO32	F-box only protein 32	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CFHR4	Complement factor H-related protein 4	Involved in complement regulation.
CFHR3	Complement factor H-related protein 3	Might be involved in complement regulation.
TRIOBP	TRIO and F-actin-binding protein	Regulates actin cytoskeletal organization, cell spreading and cell contraction by directly binding and stabilizing filamentous F-actin and prevents its depolymerization.
PLCE1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
CDH11	Cadherin-11	Cadherins are calcium-dependent cell adhesion proteins.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
TXNRD2	Thioredoxin reductase 2, mitochondrial	Involved in the control of reactive oxygen species levels and the regulation of mitochondrial redox homeostasis.
TMCO1	Calcium load-activated calcium channel	Endoplasmic reticulum (ER) calcium-selective channel preventing intracellular Ca2(+) stores from overfilling and maintaining calcium homeostasis in the ER.
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
FMNL2	Formin-like protein 2	Plays a role in the regulation of cell morphology and cytoskeletal organization.
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
KCNT2	Potassium channel subfamily T member 2	Sodium-activated and chloride-activated potassium channel.
ASPM	Abnormal spindle-like microcephaly-associated protein	Involved in mitotic spindle regulation and coordination of mitotic processes.
BICC1	Protein bicaudal C homolog 1	Putative RNA-binding protein.
C14orf39	Protein SIX6OS1	Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination.
TMEM181	Transmembrane protein 181	Mediates action of cytolethal distending toxins (CDT), which are secreted by many pathogenic bacteria.
ANTXR1	Anthrax toxin receptor 1	Plays a role in cell attachment and migration.
ELOVL5	Very long chain fatty acid elongase 5	Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.
POU6F2	POU domain, class 6, transcription factor 2	Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells.
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
THSD7A	Thrombospondin type-1 domain-containing protein 7A	Plays a role in actin cytoskeleton rearrangement.
PNPT1	Polyribonucleotide nucleotidyltransferase 1, mitochondrial	RNA-binding protein implicated in numerous RNA metabolic processes.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
AFAP1	Actin filament-associated protein 1	Can cross-link actin filaments into both network and bundle structures.
CFHR5	Complement factor H-related protein 5	Involved in complement regulation.
ZBTB41	Zinc finger and BTB domain-containing protein 41	May be involved in transcriptional regulation.
EXOC2	Exocyst complex component 2	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
SRBD1	S1 RNA-binding domain-containing protein 1	DNA- and histone-binding protein that localizes to the central axes of mitotic chromosomes.
PTCD2	Pentatricopeptide repeat-containing protein 2, mitochondrial	Involved in mitochondrial RNA maturation and mitochondrial respiratory chain function.
DNAJC24	DnaJ homolog subfamily C member 24	Stimulates the ATPase activity of several Hsp70-type chaperones.
PLEKHA7	Pleckstrin homology domain-containing family A member 7	Required for zonula adherens biogenesis and maintenance.

Protein-family classification

Druggable: 20 · Difficult: 23 · Unknown: 32 · 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
Complement	7	25.0×	1e-07
Scaffold/PPI	10	2.3×	0.049
Antibody/Immunoglobulin	5	1.9×	0.260
Transcription factor	13	1.4×	0.260
Transporter	2	2.1×	0.452
Ion channel	1	1.5×	0.738
Kinase	2	0.7×	0.975
Other/Unknown	32	0.8×	0.992
Enzyme (other)	3	0.5×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARHGEF12	Scaffold/PPI	no		DH_dom, GDS_CDC24_CS, PDZ
ANGPT1	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS
PRPF8	Other/Unknown	no		JAMM/MPN+_dom, RNaseH-like_sf, PRO8NT
GLIS1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
SEMA3C	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
SEMA3F	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub2, Ig_sub
SIX1	Transcription factor	no		HD, KN_HD, Homeodomain-like_sf
SIX6	Transcription factor	no		HD, Homeodomain-like_sf, SIX1_SD
SUPT3H	Other/Unknown	no		TFIID_TAF13, Histone-fold
ZEB1	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
PLEKHA1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, PI-Interact_SigTrans_Reg
TES	Transcription factor	no		Znf_LIM, PET_domain, PET_testin
CAV1	Other/Unknown	no		Caveolin, Caveolin_CS
CAV2	Other/Unknown	no		Caveolin, Caveolin_CS
ANKH	Other/Unknown	no		ANKH
CTTNBP2	Scaffold/PPI	no		Ankyrin_rpt, Cortactin-binding_p2_N, Ankyrin_rpt-contain_sf
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
FBXO32	Other/Unknown	no		F-box-like_dom_sf, FBX25/32
CFHR4	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFHR3	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
TRIOBP	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, M-RIP_PH
PLCE1	Enzyme (other)	yes	3.1.4.11	C2_dom, RA_dom, PLipase_C_PInositol-sp_X_dom
CDH11	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
TXNRD2	Enzyme (other)	yes	1.8.1.9	Pyr_nuc-diS_OxRdtase, Pyr_nucl-diS_OxRdtase_dimer, Thioredoxin/glutathione_Rdtase
TMCO1	Other/Unknown	no		EMC3/TMCO1, TMCO1
RBFOX1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
FMNL2	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-like
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
KCNT2	Ion channel	yes		RCK_N, K_chnl_BK_asu, K_chnl_dom
ASPM	Antibody/Immunoglobulin	yes		IQ_motif_EF-hand-BS, CH_dom, ARM-like
BICC1	Other/Unknown	no		SAM, KH_dom, KH_dom_type_1
C14orf39	Other/Unknown	no		SIX6OS1
TMEM181	Other/Unknown	no		TMEM181, WLS-like_TM, TMEM181_GOLD
ANTXR1	Other/Unknown	no		VWF_A, Anthrax_toxin_rcpt_C, Anthrax_toxin_rcpt_extracel
ELOVL5	Other/Unknown	no		ELO_fam, ELOVL5
POU6F2	Transcription factor	no		POU_dom, HD, Homeodomain-like_sf
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
THSD7A	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, TSP1_spondin_dom
PNPT1	Scaffold/PPI	no	2.7.7.8	ExoRNase_PH_dom1, S1_domain, KH_dom
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
AFAP1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, AFAP
CFHR5	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
ZBTB41	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
EXOC2	Antibody/Immunoglobulin	yes		IPT_dom, Ig-like_fold, Ig_E-set
SRBD1	Other/Unknown	no		S1_domain, YqgF/RNaseH-like_dom, RuvA_2-like
PTCD2	Other/Unknown	no		PPR_rpt, TPR-like_helical_dom_sf, PTCD2
DNAJC24	Other/Unknown	no		DnaJ_domain, DPH_MB_dom, DPH_MB_sf
PLEKHA7	Scaffold/PPI	no		WW_dom, PH_domain, PH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

71 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)	2
broad (>20)	73
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	14
primordial germ cell in gonad	10
right lobe of liver	8
liver	7
calcaneal tendon	6
lower esophagus mucosa	6
ventricular zone	5
Brodmann (1909) area 23	5
parietal pleura	5
tibia	5
sural nerve	5
lower lobe of lung	4
stromal cell of endometrium	4
parotid gland	4
cortical plate	4
endothelial cell	4
secondary oocyte	4
heart right ventricle	3
adenohypophysis	3
seminal vesicle	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARHGEF12	288	ubiquitous	marker	upper leg skin, visceral pleura, heart right ventricle
ANGPT1	250	ubiquitous	marker	lower lobe of lung, calcaneal tendon, cranial nerve II
PRPF8	145	ubiquitous	marker	adenohypophysis, pituitary gland, ventricular zone
GLIS1	134	broad	yes	stromal cell of endometrium, seminal vesicle, prostate gland
SEMA3C	289	ubiquitous	marker	mammary duct, synovial joint, calcaneal tendon
SEMA3F	289	ubiquitous	marker	cervix squamous epithelium, gingival epithelium, lower esophagus mucosa
SIX1	188	ubiquitous	marker	skeletal muscle tissue of biceps brachii, biceps brachii, parotid gland
SIX6	34	tissue_specific	marker	adenohypophysis, pituitary gland, cranial nerve II
SUPT3H	206	ubiquitous	yes	primordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis
ZEB1	287	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad
PLEKHA1	280	ubiquitous	marker	upper leg skin, sperm, Brodmann (1909) area 23
TES	267	ubiquitous	marker	cauda epididymis, seminal vesicle, saphenous vein
CAV1	287	ubiquitous	marker	parietal pleura, lower lobe of lung, pleura
CAV2	290	ubiquitous	marker	lower lobe of lung, heart right ventricle, blood vessel layer
ANKH	273	ubiquitous	marker	tibia, parotid gland, inferior vagus X ganglion
CTTNBP2	230	broad	marker	cortical plate, corpus callosum, embryo
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
FBXO32	257	ubiquitous	marker	cardiac muscle of right atrium, deltoid, tibialis anterior
CFHR4	79	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
CFHR3	127	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
TRIOBP	289	ubiquitous	marker	lower lobe of lung, cervix squamous epithelium, apex of heart
PLCE1	271	broad	marker	renal glomerulus, metanephric glomerulus, ventricular zone
CDH11	277	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, tibia
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
TXNRD2	264	ubiquitous	marker	right lobe of liver, right adrenal gland cortex, apex of heart
TMCO1	290	ubiquitous	marker	calcaneal tendon, choroid plexus epithelium, rectum
RBFOX1	220	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cortical plate
FMNL2	262	ubiquitous	marker	inferior vagus X ganglion, corpus callosum, subthalamic nucleus
CFTR	193	broad	marker	body of pancreas, gall bladder, pancreas

Protein interactions among cohort

Intra-cohort edges: 61.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFTR	7,664
CREBBP	6,959
CAV1	6,673
PRPF8	5,582
CHEK2	4,795
ZEB1	4,171
PNPT1	3,741
ETS1	3,729
TXNRD2	3,712
ABCA1	3,551

Intra-cohort edges

A	B	Sources
ABCA1	PRPF8	biogrid_interaction
AFAP1	GAS7	string_interaction
AFAP1	GMDS	string_interaction
AFAP1	SIX6	string_interaction
AFAP1	TMCO1	string_interaction
ARHGEF12	KCNT2	intact
ARMS2	CFH	string_interaction
ARMS2	CFHR1	string_interaction
ARMS2	CFHR3	string_interaction
ARMS2	CFHR4	string_interaction
ARMS2	PLEKHA1	string_interaction
CAV1	CAV2	biogrid_interaction, intact, string_interaction
CAV1	CFTR	intact
CAV1	TMCO1	string_interaction
CAV2	SRBD1	string_interaction
CAV2	TMCO1	string_interaction
CFH	CFHR1	intact
CFH	CFHR3	biogrid_interaction, intact
CFH	PLEKHA1	string_interaction
CFHR1	CFHR2	biogrid_interaction, intact
CFHR1	CFHR5	intact
CFHR1	PLEKHA1	string_interaction
CFHR1	ZBTB41	string_interaction
CFHR3	PLEKHA1	string_interaction
CFHR4	KCNT2	string_interaction
CFHR4	ZBTB41	string_interaction
CFHR5	ZBTB41	string_interaction
CFTR	CTTNBP2	string_interaction
CFTR	ELOVL5	intact
CFTR	EXOC2	intact
CFTR	LMO7	intact
CFTR	LMX1B	intact
CFTR	MYOF	intact
CFTR	PLEKHA7	intact
CFTR	PRPF8	intact
CFTR	TES	intact
CFTR	TMCO1	intact
CFTR	TRIOBP	intact
CFTR	TXNRD2	intact
COL11A1	PLEKHA7	string_interaction
CREBBP	ETS1	biogrid_interaction
DGKG	PLCE1	string_interaction
DNAJC24	ELP4	string_interaction
ELOVL5	SRBD1	string_interaction
ELOVL5	THSD7A	biogrid_interaction, intact
FOXC1	GMDS	string_interaction
FOXC1	SIX1	string_interaction
GAS7	GMDS	string_interaction
GAS7	SIX6	string_interaction
GAS7	SRBD1	string_interaction

Structural data

PDB: 34 · AlphaFold-only: 36 · No structure: 5

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CREBBP	Q92793	144
PRPF8	Q6P2Q9	101
CFTR	P13569	58
CFH	P08603	51
CHEK2	O96017	38
ETS1	P14921	21
PNPT1	Q8TCS8	11
MYOF	Q9NZM1	8
ABCA1	O95477	7
GMDS	O60547	7
ANGPT1	Q15389	5
ANTXR1	Q9H6X2	5
ARHGEF12	Q9NZN5	4
SUPT3H	O75486	4
RBFOX1	Q9NWB1	4
CFHR2	P36980	4
PLCE1	Q9P212	3
BICC1	Q9H694	3
PLEKHA7	Q6IQ23	3
TES	Q9UGI8	2
F13B	P05160	2
GAS7	O60861	2
CFHR1	Q03591	2
SIX1	Q15475	1
ZEB1	P37275	1
PLEKHA1	Q9HB21	1
CAV1	Q03135	1
TMCO1	Q9UM00	1
FMNL2	Q96PY5	1
THSD7A	Q9UPZ6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFHR3	Q02985	91.93
CDKN2B	P42772	90.12
CFHR4	Q92496	87.75
SEMA3C	Q99985	85.69
ANKH	Q9HCJ1	84.57
SEMA3F	Q13275	84.06
CFHR5	Q9BXR6	83.76
PTCD2	Q8WV60	82.95
ELOVL5	Q9NYP7	82.53
CADM2	Q8N3J6	82.53
SIX6	O95475	81.68
EXOC2	Q96KP1	80.82
FBXO32	Q969P5	80.15
TMEM181	Q9P2C4	78.28
CAV2	P51636	78.26
CDH11	P55287	77.65
DGKG	P49619	77.53
KCNT2	Q6UVM3	76.42
SRBD1	Q8N5C6	75.68
ELP4	Q96EB1	74.49
LMX1B	O60663	70.79
AFAP1	Q8N556	67.09
SH2B3	Q9UQQ2	63.45
ZBTB41	Q5SVQ8	61.91
LPP	Q93052	60.99
C14orf39	Q8N1H7	58.97
CTTNBP2	Q8WZ74	58.83
ARMS2	P0C7Q2	58.14
FOXC1	Q12948	56.09
GLIS1	Q8NBF1	53.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 321. Enrichment computed across 81 evidence-associated genes (50 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 50 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of Complement cascade	6	28.0×	2e-05	CFHR4, CFHR3, CFHR5, CFH, CFHR1, CFHR2
Kidney development	2	32.6×	0.177	SIX1, MECOM
Signaling by Nuclear Receptors	4	8.2×	0.177	CAV1, CAV2, CREBBP, ABCA1
Defective ABCA1 causes TGD	1	114.2×	0.262	ABCA1
RHO GTPases regulate CFTR trafficking	1	76.1×	0.262	CFTR
Metabolism of nitric oxide: NOS3 activation and regulation	1	45.7×	0.262	CAV1
NOSTRIN mediated eNOS trafficking	1	45.7×	0.262	CAV1
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	45.7×	0.262	CREBBP
MECP2 regulates transcription factors	1	45.7×	0.262	RBFOX1
NFE2L2 regulating inflammation associated genes	1	45.7×	0.262	CREBBP
NFE2L2 regulating ER-stress associated genes	1	45.7×	0.262	CREBBP
GDP-fucose biosynthesis	1	38.1×	0.262	GMDS
CDH11 homotypic and heterotypic interactions	1	32.6×	0.262	CDH11
Mitochondrial RNA degradation	1	32.6×	0.262	PNPT1
AMPK inhibits chREBP transcriptional activation activity	1	28.6×	0.262	PRKAG2
Synthesis of diphthamide-EEF2	1	28.6×	0.262	DNAJC24
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	28.6×	0.262	CREBBP
HDL assembly	1	28.6×	0.262	ABCA1
Formation of intermediate mesoderm	1	28.6×	0.262	FOXC1
NFE2L2 regulates pentose phosphate pathway genes	1	28.6×	0.262	CREBBP
NFE2L2 regulating MDR associated enzymes	1	28.6×	0.262	CREBBP
Regulation of NFE2L2 gene expression	1	28.6×	0.262	CREBBP
Lipophagy	1	25.4×	0.262	PRKAG2
Regulation of CDH11 mRNA translation by microRNAs	1	25.4×	0.262	CDH11
Linoleic acid (LA) metabolism	1	22.8×	0.262	ELOVL5
Activation of PPARGC1A (PGC-1alpha) by phosphorylation	1	22.8×	0.262	PRKAG2
Regulation of FOXO transcriptional activity by acetylation	1	22.8×	0.262	CREBBP
Regulation of CDH11 function	1	20.8×	0.262	CDH11
Regulation of CDH11 gene transcription	1	20.8×	0.262	CDH11
Formation of the ureteric bud	2	19.9×	0.262	SIX1, FOXC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 75 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
complement activation	6	49.9×	1e-06	CFHR4, CFHR3, CFHR5, CFH, CFHR1, CFHR2
obsolete cytolysis by host of symbiont cells	3	84.3×	0.002	CFHR5, CFHR1, CFHR2
regulation of entry of bacterium into host cell	2	89.9×	0.026	CAV1, EXOC2
ventricular cardiac muscle tissue morphogenesis	3	28.1×	0.026	COL11A1, PTCD2, FOXC1
negative regulation of protein binding	3	25.0×	0.026	CFHR5, CFHR1, CFHR2
kidney development	5	9.4×	0.026	SIX1, BICC1, PTCD2, FOXC1, PKHD1
regulation of skeletal muscle satellite cell proliferation	2	74.9×	0.028	ANGPT1, SIX1
caveola assembly	2	56.2×	0.046	CAV1, CAV2
regulation of fatty acid metabolic process	2	49.9×	0.053	CAV1, PRKAG2
homeostatic process	2	44.9×	0.058	CREBBP, PKHD1
embryonic skeletal system morphogenesis	3	15.7×	0.058	SIX1, ZEB1, COL11A1
receptor-mediated endocytosis of virus by host cell	2	40.9×	0.060	CAV1, CAV2
response to oxygen radical	1	224.7×	0.092	TXNRD2
regulation of mesenchymal cell proliferation	1	224.7×	0.092	ZEB1
skeletal muscle hypertrophy	1	224.7×	0.092	MYOC
negative regulation of skeletal muscle cell proliferation	1	224.7×	0.092	CAV2
RNA import into mitochondrion	1	224.7×	0.092	PNPT1
negative regulation of asymmetric cell division	1	224.7×	0.092	ASPM
nuclear polyadenylation-dependent mRNA catabolic process	1	224.7×	0.092	PNPT1
glomerular epithelium development	1	224.7×	0.092	FOXC1
mesonephric tubule formation	1	224.7×	0.092	SIX1
mesenchymal cell proliferation involved in ureter development	1	224.7×	0.092	SIX1
cardiac endothelial to mesenchymal transition	1	224.7×	0.092	SEMA3C
positive regulation of hematopoietic stem cell differentiation	1	224.7×	0.092	FOXC1
regulation of cholangiocyte proliferation	1	224.7×	0.092	PKHD1
regulation of macrophage migration inhibitory factor signaling pathway	1	224.7×	0.092	ANGPT1
mitochondrial RNA 5’-end processing	1	112.3×	0.092	PNPT1
regulation of the force of heart contraction by chemical signal	1	112.3×	0.092	CAV1
aortic valve formation	1	112.3×	0.092	CDH11
apoptotic process involved in outflow tract morphogenesis	1	112.3×	0.092	FOXC1

Therapeutics

Drugs indicated for this disease

30 approved, 14 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetazolamide	Approved (phase 4)
Acetylcholine	Approved (phase 4)
Apraclonidine	Approved (phase 4)
Betaxolol	Approved (phase 4)
Bimatoprost	Approved (phase 4)
Brimonidine	Approved (phase 4)
Brinzolamide	Approved (phase 4)
Carteolol	Approved (phase 4)
Clonidine	Approved (phase 4)
Dapiprazole	Approved (phase 4)
Demecarium	Approved (phase 4)
Dichlorphenamide	Approved (phase 4)
Dipivefrin	Approved (phase 4)
Dorzolamide	Approved (phase 4)
Echothiophate	Approved (phase 4)
Epinephrine	Approved (phase 4)
Guanethidine	Approved (phase 4)
Isoflurophate	Approved (phase 4)
Latanoprost	Approved (phase 4)
Latanoprostene Bunod	Approved (phase 4)
Levobunolol	Approved (phase 4)
Methazolamide	Approved (phase 4)
Metipranolol	Approved (phase 4)
Mitomycin	Approved (phase 4)
Neostigmine	Approved (phase 4)
Physostigmine	Approved (phase 4)
Pilocarpine	Approved (phase 4)
Tafluprost	Approved (phase 4)
Timolol	Approved (phase 4)
Travoprost	Approved (phase 4)
Aceclidine	Phase 3 (in late-stage trials)
Aflibercept	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Netarsudil	Phase 3 (in late-stage trials)
Ofloxacin	Phase 3 (in late-stage trials)
Omidenepag Isopropyl	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Ranibizumab	Phase 3 (in late-stage trials)
Ripasudil	Phase 3 (in late-stage trials)
Sildenafil	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): AMA0076, Betamethasone, Cannabinol, Ciliary Neurotrophic Factor, Cyclosporine, Piclidenoson, Sodium Chloride, Triamcinolone Acetonide, Zinpentraxin Alfa.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 4 · Phased (≥1): 6 · Undrugged: 69

Druggability breadth: 28 of 81 evidence-associated genes (35%) 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
CHEK2	NERATINIB
CFTR	IVACAFTOR
CREBBP	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHEK2	30	4
CFTR	14	4
CREBBP	13	4
TXNRD2	3	3
PRPF8	1	2
GMDS	1	2
ARHGEF12	0	0
ANGPT1	0	0
GLIS1	0	0
SEMA3C	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2
GEFITINIB	4	CHEK2
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
DOVITINIB	3	CHEK2
LESTAURTINIB	3	CHEK2
RUBOXISTAURIN	3	CHEK2
CURCUMIN	3	CREBBP, TXNRD2
RUTIN	3	CFTR
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR
PAPAVERINE	3	CREBBP
EPIGALOCATECHIN GALLATE	3	CREBBP
MOLIBRESIB	2	CREBBP, GMDS, PRPF8
DORAMAPIMOD	2	CHEK2
FORETINIB	2	CHEK2
SU-014813	2	CHEK2
CENISERTIB	2	CHEK2
ILORASERTIB	2	CHEK2
CEP-11981	2	CHEK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
CHEK2	690	Binding:687, Functional:2, ADMET:1
CREBBP	687	Binding:644, Functional:43
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
TXNRD2	91	Binding:76, Functional:15
MYOF	14	Binding:14
SIX1	12	Binding:12
ARHGEF12	11	Binding:11
PRPF8	8	Binding:8
GMDS	8	Binding:8
KCNT2	7	Binding:7
CAV1	5	Binding:5
ELOVL5	5	Binding:5
DGKG	5	Binding:5
F13B	3	Binding:3
TES	2	Binding:2
ABCA1	2	Binding:2
ANGPT1	1	Binding:1
PLEKHA1	1	Binding:1
TMCO1	1	Binding:1
PLEKHA7	1	Binding:1
MECOM	1	Binding:1
CFH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
PLCE1	3.1.4.11	phosphoinositide phospholipase C
TXNRD2	1.8.1.9	thioredoxin-disulfide reductase (NADPH)
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase
PNPT1	2.7.7.8	polyribonucleotide nucleotidyltransferase
CREBBP	2.3.1.48	histone acetyltransferase
DGKG	2.7.1.107	diacylglycerol kinase (ATP)
GMDS	4.2.1.47	GDP-mannose 4,6-dehydratase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHEK2	690
CFTR	520
CREBBP	687

Pharmacogenomics

Cohort genes with a PharmGKB record: 72; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

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)
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2
GEFITINIB	4	CHEK2
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
DOVITINIB	3	CHEK2
LESTAURTINIB	3	CHEK2
RUBOXISTAURIN	3	CHEK2
CURCUMIN	3	CREBBP, TXNRD2
RUTIN	3	CFTR
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR
PAPAVERINE	3	CREBBP
EPIGALOCATECHIN GALLATE	3	CREBBP
MOLIBRESIB	2	CREBBP, GMDS, PRPF8
DORAMAPIMOD	2	CHEK2
FORETINIB	2	CHEK2
SU-014813	2	CHEK2
CENISERTIB	2	CHEK2
ILORASERTIB	2	CHEK2
CEP-11981	2	CHEK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CHEK2, CFTR, CREBBP
B	Phased (≥1) drug, not yet approved	3	PRPF8, TXNRD2, GMDS
C	Druggable family + PDB, no drug	6	PLCE1, ABCA1, F13B, CFH, CFHR1, CFHR2
D	Druggable family + AlphaFold only, no drug	10	SEMA3C, SEMA3F, CFHR4, CFHR3, KCNT2, ASPM, CFHR5, EXOC2, DGKG, CADM2
E	Difficult family or no structure, no drug	53	ARHGEF12, ANGPT1, GLIS1, SIX1, SIX6, SUPT3H, ZEB1, ELP4, PLEKHA1, TES (+43 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AFAP1	0	GMDS
FOXC1	0	GMDS
ARHGEF12	11	—
ANGPT1	1	—
GLIS1	0	—
SEMA3C	0	—
SEMA3F	0	—
SIX1	12	—
SIX6	0	—
SUPT3H	0	—
ZEB1	0	—
ELP4	0	—
PLEKHA1	1	—
TES	2	—
CAV1	5	—
CAV2	0	—
ANKH	0	—
CTTNBP2	0	—
FBXO32	0	—
CFHR4	0	—
CFHR3	0	—
TRIOBP	0	—
PLCE1	0	—
CDH11	0	—
CDKN2B	0	—
TMCO1	1	—
RBFOX1	0	—
FMNL2	0	—
KCNT2	7	—
ASPM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,034.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	701
PHASE4	142
PHASE3	80
PHASE2	48
PHASE1	29
PHASE1/PHASE2	17
PHASE2/PHASE3	9
EARLY_PHASE1	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04007276	PHASE4	NOT_YET_RECRUITING	The Effect of Lumify™ on Ocular Redness, Intraocular Pressure, and Eyelid Position in Glaucoma Patients
NCT04957329	PHASE4	RECRUITING	Effect of Benzalkonium Chloride Preserved and Preservative-free Latanoprost Eye Drops on Conjunctival Goblet Cells
NCT05344274	PHASE4	RECRUITING	Retinal Blood Flow and Autoregulation
NCT06017362	PHASE4	RECRUITING	Clinical Trial to Determine the Efficacy and Safety of Insulin Eye Drops in Dry Eye in Patients with Topical Hypotensors
NCT06761313	PHASE4	ACTIVE_NOT_RECRUITING	Triplenex (triple Fixed Combination) Use Evaluation in Patients with Glaucoma
NCT06792422	PHASE4	RECRUITING	A Study Investigating Oral Semaglutide in People with Open-Angle Glaucoma
NCT07174401	PHASE4	NOT_YET_RECRUITING	Rocklatan Retinal Perfusion OCT Study
NCT07209410	PHASE4	RECRUITING	Evaluating Injection With the Use of Brimonidine Tartrate Ophthalmic 0.025% on Patients Using Netarsudil 0.02%/Latanoprost 0.005% to Treat Glaucoma
NCT07217678	PHASE4	RECRUITING	Biomarkers of Ocular Surface Damage in the Setting of Topical Ocular Hypotensive Medication Use
NCT07465913	PHASE4	RECRUITING	Rocklatan vs Latanoprost Post-DSLT
NCT07588152	PHASE4	NOT_YET_RECRUITING	Imaging the Effects of Netarsudil (Rhopressa) on the Trabecular Meshwork in Glaucoma and Ocular Hypertension
NCT00061503	PHASE4	COMPLETED	Mechanism of Action of TRAVATAN 0.004% in Subjects With Glaucoma or Ocular Hypertension
NCT00143208	PHASE4	COMPLETED	Evaluation Of Intraocular Pressure Lowering-Effect Of Xalacom In Patients With Poag Or Oh.
NCT00224289	PHASE4	COMPLETED	Effect of Age on Latanoprost 0.005% in Patients With Glaucoma
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00329095	PHASE4	COMPLETED	An Evaluation of Use of Topical Ocular Hypotensive Medication by Compliance
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00346489	PHASE4	COMPLETED	Outcomes of Intraoperative 5-Fluorouracil Versus Mitomycin C
NCT00347035	PHASE4	TERMINATED	INFLUENCE OF TOPICAL INDOMETHACIN ON HYPOTHENSIVE EFFECT OF BRIMONIDINE
NCT00347802	PHASE4	COMPLETED	Diurnal Curves With Bimatoprost 0.03% Versus Travoprost 0.004%
NCT00347841	PHASE4	COMPLETED	Efficacy of Bimatoprost 0.03% in Patients Who Are Low-Responders to Latanoprost
NCT00348023	PHASE4	COMPLETED	Bimatoprost Monotherapy vs. Dual Therapy With Travoprost and Timolol in Patients With Glaucoma and Ocular Hypertension
NCT00348062	PHASE4	COMPLETED	A Multicenter Evaluation of Methods to Reduce Hyperemia Associated With Bimatoprost Therapy for Glaucoma or Ocular Hypertension
NCT00348400	PHASE4	COMPLETED	Brimonidine Purite 0.15% Versus Dorzolamide 2% Used as Adjunctive Therapy to Latanoprost
NCT00351429	PHASE4	COMPLETED	Study of PGA Suture in Ophthalmology
NCT00376974	PHASE4	UNKNOWN	The Effect of Education on Patient Compliance
NCT00379834	PHASE4	COMPLETED	12-Month Stability of Diurnal IOP Control on Cosopt
NCT00382226	PHASE4	COMPLETED	IOP-Lowering Efficacy of Brinzolamide 1.0% Added to Travoprost 0.004%/Timolol 0.5% Fixed Combination as Adjunctive Therapy
NCT00404729	PHASE4	COMPLETED	Neural Conduction Along the Visual Pathways After Oral Treatment With Citicoline in Patients With Optic Nerve Diseases
NCT00440011	PHASE4	COMPLETED	Bimatoprost 0.03% Versus Travoprost 0.004% in Patients Currently on Latanoprost 0.005%
NCT00440141	PHASE4	COMPLETED	Brimonidine 0.1% Versus Brinzolamide 1% as Adjunctive Therapy to Latanoprost 0.005%
NCT00442312	PHASE4	UNKNOWN	Combigan Ophthalmic Solution(Brimonidine 0.2% and Timolol 0.5%)With Latanoprost Compared With Latanoprost Monotherapy
NCT00444184	PHASE4	COMPLETED	24-hour Intraocular Pressure Control With Travoprost/Timolol Fixed Combination Versus Travoprost
NCT00444665	PHASE4	COMPLETED	Examining The Efficacy, Safety And Improved Tolerability Of Travoprost BAK Free Ophthalmic Solution (Travatan-Z) Compared To Prior Prostaglandin Therapy
NCT00449098	PHASE4	UNKNOWN	Ologen (OculusGen)-Glaucoma MMC Control Trial in India
NCT00466479	PHASE4	COMPLETED	Brimonidine vs ALTP in Progressing Human Glaucoma
NCT00468429	PHASE4	UNKNOWN	Subconjunctival Bevacizumab to Prevent Bleb Failure After Glaucoma Filtration Surgery
NCT00468988	PHASE4	COMPLETED	Short Term Comparative Study of Xalatan With Benzalkonium Chloride vs. Travatan Z Without Benzalkonium Chloride in Healthy Volunteers
NCT00471380	PHASE4	COMPLETED	A Phase IV Study of Travoprost + Brinzolamide to Treat Glaucoma or Ocular Hypertension
NCT00485238	PHASE4	UNKNOWN	ALPI vs Medical Therapy Effects on Optic Nerve Structure & Function

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TIMOLOL	4	86
BRIMONIDINE	4	76
LATANOPROST	4	51
TRAVOPROST	4	37
BIMATOPROST	4	32
BRINZOLAMIDE	4	23
DORZOLAMIDE	4	17
MITOMYCIN	4	8
RANIBIZUMAB	4	6
NIACINAMIDE	4	5
BEVACIZUMAB	4	4
HYPROMELLOSE	4	4
FLUOROURACIL	4	3
KETOROLAC	4	3
NETARSUDIL	4	3
TAFLUPROST	4	3
ACETAZOLAMIDE	4	2
PILOCARPINE	4	2
PREDNISOLONE	4	2
ROSUVASTATIN	4	2
TRIAMCINOLONE ACETONIDE	4	2
AFLIBERCEPT	4	1
APRACLONIDINE	4	1
APRACLONIDINE HYDROCHLORIDE	4	1
BOSENTAN	4	1
BROMFENAC	4	1
CENEGERMIN	4	1
CHLORPROMAZINE	4	1
CHLORPROMAZINE HYDROCHLORIDE	4	1
FLUOROMETHOLONE	4	1