Retinal disorder

Summary

Retinal disorder (MONDO:0005283) is a disease (an umbrella term covering 32 Mondo subtypes) with 75 cohort genes (113 GWAS associations across 72 studies) and 27 clinical trials. The dominant Reactome pathway is The canonical retinoid cycle in rods (twilight vision) (6 cohort genes). Top therapeutic interventions include fluorescein, ketamine, and nitroglycerin.

At a glance

• Umbrella term: 32 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 113
• ClinVar variants: 245
• Clinical trials: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinal disorder
Mondo ID	MONDO:0005283
EFO	EFO:0003839
MeSH	D012164
DOID	DOID:5679
NCIT	C26875, C62601
SNOMED CT	29555009
UMLS	C0035309
MedGen	11209
Anatomy (UBERON)	UBERON:0000966
Is cancer (heuristic)	no

Also known as: eye disease of retina · retina eye disease · retinopathy

Data availability: 245 ClinVar variants · 113 GWAS associations (72 studies) · 6 GenCC gene-disease records.

Disease family

An umbrella term covering 32 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder

Related subtypes (71): congenital nervous system disorder, central nervous system disorder, autoimmune disorder of the nervous system, cranial nerve neuropathy, peripheral nervous system disorder, neuronitis, diplegia of upper limb, developmental disability, restless legs syndrome, movement disorder, toxic encephalopathy, Barre-Lieou syndrome, Gerstmann syndrome, drug-induced akathisia, drug-induced dyskinesia, stiff-person syndrome, Worster-Drought syndrome, corneal-cerebellar syndrome, pachygyria-intellectual disability-epilepsy syndrome, porencephaly-cerebellar hypoplasia-internal malformations syndrome, symmetrical thalamic calcifications, neonatal brainstem dysfunction, primary orthostatic hypotension, rippling muscle disease with myasthenia gravis, periodic paralysis, qualitative or quantitative protein defects in neuromuscular diseases, specific learning disability, cerebellar hypoplasia-tapetoretinal degeneration syndrome, locked-in syndrome, dopa-responsive dystonia, idiopathic recurrent stupor, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, spontaneous periodic hypothermia, Sydenham chorea, duplication of the pituitary gland, Balint syndrome, paraneoplastic neurologic syndrome, persistent idiopathic facial pain, serotonin syndrome, hypothalamic adipsic hypernatraemia syndrome, exercise-induced malignant hyperthermia, perineural cyst, neuromuscular disease, neuromyelitis optica, AL amyloidosis, AA amyloidosis, neuroleptic malignant syndrome, infectious disorder of the nervous system, central nervous system malformation, synaptopathy, nervous system neoplasm, sensory ganglionopathy, radiculitis, wet beriberi, perceptual disorders, prepubertal anorexia nervosa, neurocutaneous syndrome, neurovascular disorder, Wallerian degeneration, nervous system injury, neurosarcoidosis, neuroendocrine disorder, tubulinopathy, atactic disorder, hereditary neurological disease, meningitis-retention syndrome, KIF1A related neurological disorder, neurological pain disorder, neurodevelopmental disorder, post 5-alpha-reductase inhibitors treatment syndrome, post-selective serotonin reuptake inhibitor sexual dysfunction

Subtypes (32): retinal ischemia, rubeosis iridis, retinal vascular disorder, retinitis, retinal nerve fiber layer disorder, retinal edema, retinal degeneration, night blindness, hypertensive retinopathy, macular holes, retinal detachment, iris hypoplasia with glaucoma, angioid streaks, bradyopsia, myopic macular degeneration, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, congenital retinal arteriovenous communication, Eales disease, central serous chorioretinopathy, achromatopsia, cancer-associated retinopathy, persistent placoid maculopathy, inherited vitreoretinopathy, retina neoplasm, retinal ciliopathy, melanoma associated retinopathy, isolated foveal hypoplasia, acute macular neuroretinopathy, autoimmune retinopathy, proliferative vitreoretinopathy, isolated chorioretinal dystrophy, torpedo maculopathy

Genetics & variants

GWAS landscape

113 GWAS associations across 72 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1329424	1e-323	CFH	T	0.21
rs12038333	2e-250	CFH	G	0.17
rs10490924	9e-208	HTRA1-AS1, ARMS2	G	0.2
chr1:196660995	8e-188		A	0.46
rs579745	2e-176	CFH	A	0.42
rs11200630	7e-127	HTRA1-AS1	T	0.15
chr10:122454155	5e-104		A	0.27
chr1:196694783	6e-79		T	0.21
chr10:124214976	6e-70		G	0.32
chr6:32659703	4e-43		A	0.3
chr10:112998590	9e-37		T	0.27
chr11:92623608	1e-36		A	0.18
chr3:154024897	7e-34		T	0.13
rs10765567	8e-33	FAT3	A	0.15
rs115803211	1e-32	MIR9-2HG	T	0.64
rs184006295	2e-29	HLA-DRB1 - HLA-DQA1	C	0.34
rs556679	2e-29	C2	C	0.1
rs13319067	1e-28	DHX36	T	0.12
rs2230199	3e-27	C3	G	0.07
rs11864330	7e-27	FOXL1 - LINC02188	G	0.14
chr6:31924880	2e-26		G	0.35
rs34825161	5e-24	RPL7AP36 - RPL21P62	G	0.12
rs8181047	5e-21	CDKN2B-AS1	A	0.1
chr9:22056499	6e-21		G	0.1
rs4844390	3e-19	CD46, MIR29B2CHG	A	0.07
chr19:6718376	1e-18		C	0.11
rs6657476	3e-18	CD46, MIR29B2CHG	G	0.06
rs510497	5e-18	CPLX4	T	0.1
chr9:113801441	2e-17		G	0.11
rs3739706	4e-17	LPAR1	A	0.11

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475847	Verma A	2024	88,461	323,715	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477623	Verma A	2024	20,545	89,438	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475854	Verma A	2024	20,138	419,008	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473427	UK Biobank Whole-Genome Sequencing Consortium	2025	17,813	440,627	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST010548	Vujkovic M	2020	13,881	123,538	Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.
GCST90475845	Verma A	2024	12,993	431,515	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477636	Verma A	2024	12,949	423,316	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477621	Verma A	2024	8,808	45,996	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475855	Verma A	2024	8,539	430,460	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475853	Verma A	2024	6,777	439,411	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	41
low_freq (0.01-0.05)	1
rare (<0.01)	2
unknown	6

Functional consequences

Consequence	Count
intron_variant	22
unknown	19
intergenic_variant	4
missense_variant	3
non_coding_transcript_exon_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1329424	1	196677046	T>A,C,G	0.382	intron_variant	CFH	1e-323	Tier 4: intronic/intergenic
rs12038333	1	196703324	G>A,T	0.37	intron_variant	CFH	2e-250	Tier 4: intronic/intergenic
rs10490924	10	122454932	G>C,T	0.215	missense_variant	HTRA1-AS1, ARMS2	9e-208	Tier 1: coding
chr1:196660995				0.385			8e-188	Tier 4: intronic/intergenic
rs579745	1	196695446	A>C,T	0.341	intron_variant	CFH	2e-176	Tier 4: intronic/intergenic
rs11200630	10	122450168	T>C,G	0.209	intron_variant	HTRA1-AS1	7e-127	Tier 4: intronic/intergenic
chr10:122454155							5e-104	Tier 4: intronic/intergenic
chr1:196694783							6e-79	Tier 4: intronic/intergenic
chr10:124214976				0.21			6e-70	Tier 4: intronic/intergenic
chr6:32659703							4e-43	Tier 4: intronic/intergenic
chr10:112998590							9e-37	Tier 4: intronic/intergenic
chr11:92623608				0.381			1e-36	Tier 4: intronic/intergenic
chr3:154024897				0.345			7e-34	Tier 4: intronic/intergenic
rs10765567	11	92868743	A>T	0.314	intron_variant	FAT3	8e-33	Tier 4: intronic/intergenic
rs115803211	5	88611619	T>C,G	0.059	intron_variant	MIR9-2HG	1e-32	Tier 4: intronic/intergenic
rs184006295	6	32591185	C>T	0.109	intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-29	Tier 4: intronic/intergenic
rs556679	6	31926578	C>T	0.112	intron_variant	C2	2e-29	Tier 4: intronic/intergenic
rs13319067	3	154304652	T>A,C	0.28	intron_variant	DHX36	1e-28	Tier 4: intronic/intergenic
rs2230199	19	6718376	G>A,C,T	0.209	missense_variant	C3	3e-27	Tier 1: coding
rs11864330	16	86690782	G>A,C	0.222	intron_variant	FOXL1 - LINC02188	7e-27	Tier 4: intronic/intergenic
chr6:31924880				0.093			2e-26	Tier 4: intronic/intergenic
rs34825161	6	10185180	G>A,C	0.239	intergenic_variant	RPL7AP36 - RPL21P62	5e-24	Tier 4: intronic/intergenic
rs8181047	9	22064466	A>C,G,T	0.256	intron_variant	CDKN2B-AS1	5e-21	Tier 4: intronic/intergenic
chr9:22056499				0.477			6e-21	Tier 4: intronic/intergenic
rs4844390	1	207761504	A>G	0.177	non_coding_transcript_exon_variant	CD46, MIR29B2CHG	3e-19	Tier 4: intronic/intergenic
chr19:6718376							1e-18	Tier 4: intronic/intergenic
rs6657476	1	207786759	G>T	0.21	intron_variant	CD46, MIR29B2CHG	3e-18	Tier 4: intronic/intergenic
rs510497	18	59280034	T>C	0.261	intergenic_variant	CPLX4	5e-18	Tier 4: intronic/intergenic
chr9:113801441				0.188			2e-17	Tier 4: intronic/intergenic
rs3739706	9	111030717	A>G,T	0.164	intron_variant	LPAR1	4e-17	Tier 4: intronic/intergenic

ClinVar germline variants

245 retrieved; paginated sample, class counts are floors:

82 pathogenic/likely pathogenic, 72 pathogenic, 36 conflicting classifications of pathogenicity, 24 uncertain significance, 22 likely pathogenic, 3 benign/likely benign, 3 likely benign, 1 benign, 1 pathogenic/likely pathogenic/established risk allele, 1 pathogenic/likely pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1001082	NM_000350.3(ABCA4):c.1019A>C (p.Tyr340Ser)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1275763	NM_000350.3(ABCA4):c.5578C>T (p.Arg1860Trp)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
193580	NM_000350.3(ABCA4):c.1253T>C (p.Phe418Ser)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212727	NM_000350.3(ABCA4):c.1964T>G (p.Phe655Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
283573	NM_000350.3(ABCA4):c.6729+5_6729+19del	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374183	NM_000350.3(ABCA4):c.5175dup (p.Thr1726fs)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4819965	NM_000350.3(ABCA4):c.973_974del (p.Gly325fs)	ABCA4	Pathogenic	criteria provided, single submitter
635989	NM_000350.3(ABCA4):c.6386+1G>A	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
7882	NM_000350.3(ABCA4):c.6079C>T (p.Leu2027Phe)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7888	NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu)	ABCA4	Pathogenic	reviewed by expert panel
7894	NM_000350.3(ABCA4):c.3113C>T (p.Ala1038Val)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7900	NM_000350.3(ABCA4):c.1715G>A (p.Arg572Gln)	ABCA4	Pathogenic	reviewed by expert panel
7904	NM_000350.3(ABCA4):c.4139C>T (p.Pro1380Leu)	ABCA4	Pathogenic	reviewed by expert panel
7907	NM_000350.3(ABCA4):c.6088C>T (p.Arg2030Ter)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
859348	NM_000350.3(ABCA4):c.859-9T>C	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
92867	NM_000350.3(ABCA4):c.3322C>T (p.Arg1108Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
92870	NM_000350.3(ABCA4):c.5461-10T>C	ABCA4	Pathogenic	reviewed by expert panel
966011	NM_000350.3(ABCA4):c.735T>G (p.Tyr245Ter)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
969178	NM_000350.3(ABCA4):c.4070C>T (p.Ala1357Val)	ABCA4	Pathogenic/Likely pathogenic/Established risk allele	criteria provided, multiple submitters, no conflicts
99043	NM_000350.3(ABCA4):c.1317G>A (p.Trp439Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
99065	NM_000350.3(ABCA4):c.161G>A (p.Cys54Tyr)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99070	NM_000350.3(ABCA4):c.1648G>A (p.Gly550Arg)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99108	NM_000350.3(ABCA4):c.1957C>T (p.Arg653Cys)	ABCA4	Pathogenic	reviewed by expert panel
99173	NM_000350.3(ABCA4):c.2912C>A (p.Thr971Asn)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99196	NM_000350.3(ABCA4):c.3064G>A (p.Glu1022Lys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99260	NM_000350.3(ABCA4):c.4222T>C (p.Trp1408Arg)	ABCA4	Pathogenic/Likely pathogenic; other	criteria provided, multiple submitters, no conflicts
99317	NM_000350.3(ABCA4):c.4773+1G>T	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
99349	NM_000350.3(ABCA4):c.5161_5162del (p.Thr1721fs)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
99428	NM_000350.3(ABCA4):c.6089G>A (p.Arg2030Gln)	ABCA4	Pathogenic	reviewed by expert panel
99452	NM_000350.3(ABCA4):c.6342G>A (p.Val2114=)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 28 · Orphanet: 138 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
TENM4	TENM4	GWAS

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
HBS1L	Moderate	Autosomal recessive	retinal disorder
RNF7	Moderate	Autosomal recessive	retinal disorder	9
SAG	Moderate	Autosomal recessive	retinal disorder	9
DHX32	Limited	Autosomal recessive	retinal disorder	3
DSCAML1	Limited	Autosomal recessive	retinal disorder	4
SYTL4	Limited	X-linked	retinal disorder
TMED7	Limited	Autosomal recessive	retinal disorder

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SAG	Orphanet:75382	Oguchi disease
SAG	Orphanet:791	Retinitis pigmentosa
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa
GRK1	Orphanet:75382	Oguchi disease
RLBP1	Orphanet:227796	Fundus albipunctatus
RLBP1	Orphanet:52427	Retinitis punctata albescens
RLBP1	Orphanet:791	Retinitis pigmentosa
RLBP1	Orphanet:85128	Bothnia retinal dystrophy
RP1	Orphanet:791	Retinitis pigmentosa
RP2	Orphanet:791	Retinitis pigmentosa
RPE65	Orphanet:364055	Severe early-childhood-onset retinal dystrophy
RPE65	Orphanet:65	Leber congenital amaurosis
RPE65	Orphanet:791	Retinitis pigmentosa
RPGR	Orphanet:1872	Cone rod dystrophy
RPGR	Orphanet:244	Primary ciliary dyskinesia
RPGR	Orphanet:247522	Primary ciliary dyskinesia-retinitis pigmentosa syndrome
RPGR	Orphanet:49382	Achromatopsia
RPGR	Orphanet:791	Retinitis pigmentosa
SLC18A2	Orphanet:352649	Brain dopamine-serotonin vesicular transport disease
SRC	Orphanet:480851	Hereditary thrombocytopenia with early-onset myelofibrosis
SSBP1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
CDKL5	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
CDKL5	Orphanet:3095	Atypical Rett syndrome
CDKL5	Orphanet:505652	CDKL5-deficiency disorder
CDKL5	Orphanet:697160	Infantile epileptic spasms syndrome
TCF7L2	Orphanet:528084	Non-specific syndromic intellectual disability
TIMP3	Orphanet:59181	Sorsby fundus dystrophy
MED12	Orphanet:1415	Hardikar syndrome
MED12	Orphanet:293707	Blepharophimosis-intellectual disability syndrome, MKB type
MED12	Orphanet:776	Lujan-Fryns syndrome
MED12	Orphanet:777	X-linked non-syndromic intellectual disability
MED12	Orphanet:93932	FG syndrome type 1
CFAP410	Orphanet:1872	Cone rod dystrophy
CFAP410	Orphanet:653709	Cone rod dystrophy-short stature syndrome
CFAP410	Orphanet:803	Amyotrophic lateral sclerosis
USH2A	Orphanet:231178	Usher syndrome type 2
USH2A	Orphanet:791	Retinitis pigmentosa
CLRN1	Orphanet:231183	Usher syndrome type 3
CLRN1	Orphanet:791	Retinitis pigmentosa
BEST1	Orphanet:1243	Best vitelliform macular dystrophy
BEST1	Orphanet:139455	Autosomal recessive bestrophinopathy
BEST1	Orphanet:263347	MRCS syndrome
BEST1	Orphanet:3086	Autosomal dominant vitreoretinochoroidopathy
BEST1	Orphanet:35612	Nanophthalmos
BEST1	Orphanet:791	Retinitis pigmentosa
BEST1	Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy
RPGRIP1	Orphanet:1872	Cone rod dystrophy
RPGRIP1	Orphanet:564	Meckel syndrome

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	9
gwas_and_clinvar	1
multi_evidence	65

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF7	HGNC:10070	ENSG00000114125	Q9UBF6	RING-box protein 2	gencc,clinvar
SAG	HGNC:10521	ENSG00000130561	P10523	S-arrestin	gencc,clinvar
TENM4	HGNC:29945	ENSG00000149256	Q6N022	Teneurin-4	gwas,clinvar
DSCAML1	HGNC:14656	ENSG00000177103	Q8TD84	Cell adhesion molecule DSCAML1	gencc
SYTL4	HGNC:15588	ENSG00000102362	Q96C24	Synaptotagmin-like protein 4	gencc
DHX32	HGNC:16717	ENSG00000089876	Q7L7V1	Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32	gencc
TMED7	HGNC:24253	ENSG00000134970	Q9Y3B3	Transmembrane emp24 domain-containing protein 7	gencc
HBS1L	HGNC:4834	ENSG00000112339	Q9Y450	HBS1-like protein	gencc
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
GRK1	HGNC:10013	ENSG00000185974	Q15835	Rhodopsin kinase GRK1	clinvar
RLBP1	HGNC:10024	ENSG00000140522	P12271	Retinaldehyde-binding protein 1	clinvar
RP1	HGNC:10263	ENSG00000104237	P56715	Oxygen-regulated protein 1	clinvar
RP2	HGNC:10274	ENSG00000102218	O75695	Protein XRP2	clinvar
RPE65	HGNC:10294	ENSG00000116745	Q16518	Retinoid isomerohydrolase	clinvar
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	clinvar
SLC18A2	HGNC:10935	ENSG00000165646	Q05940	Synaptic vesicular amine transporter	gwas
SRC	HGNC:11283	ENSG00000197122	P12931	Proto-oncogene tyrosine-protein kinase Src	gwas
SSBP1	HGNC:11317	ENSG00000106028	Q04837	Single-stranded DNA-binding protein, mitochondrial	clinvar
CDKL5	HGNC:11411	ENSG00000008086	O76039	Cyclin-dependent kinase-like 5	clinvar
SYN3	HGNC:11496	ENSG00000185666	O14994	Synapsin-3	clinvar
TCF7L2	HGNC:11641	ENSG00000148737	Q9NQB0	Transcription factor 7-like 2	gwas
TIMP3	HGNC:11822	ENSG00000100234	P35625	Metalloproteinase inhibitor 3	clinvar
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	clinvar
CFAP410	HGNC:1260	ENSG00000160226	O43822	Cilia- and flagella-associated protein 410	clinvar
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	clinvar
CLRN1	HGNC:12605	ENSG00000163646	P58418	Clarin-1	clinvar
BEST1	HGNC:12703	ENSG00000167995	O76090	Bestrophin-1	clinvar
RPGRIP1	HGNC:13436	ENSG00000092200	Q96KN7	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	clinvar
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	clinvar
CACNA1F	HGNC:1393	ENSG00000102001	O60840	Voltage-dependent L-type calcium channel subunit alpha-1F	clinvar
OR12D3	HGNC:13963	ENSG00000112462	Q9UGF7	Olfactory receptor 12D3	gwas
HDAC9	HGNC:14065	ENSG00000048052	Q9UKV0	Histone deacetylase 9	gwas
PCDH18	HGNC:14268	ENSG00000189184	Q9HCL0	Protocadherin-18	gwas
CDHR1	HGNC:14550	ENSG00000148600	Q96JP9	Cadherin-related family member 1	clinvar
PRPF31	HGNC:15446	ENSG00000105618	Q8WWY3	U4/U6 small nuclear ribonucleoprotein Prp31	clinvar
NBAS	HGNC:15625	ENSG00000151779	A2RRP1	NBAS subunit of NRZ tethering complex	clinvar
RP1L1	HGNC:15946	ENSG00000183638	Q8IWN7	Retinitis pigmentosa 1-like 1 protein	clinvar
CLASP1	HGNC:17088	ENSG00000074054	Q7Z460	CLIP-associating protein 1	clinvar
ADAMTS18	HGNC:17110	ENSG00000140873	Q8TE60	A disintegrin and metalloproteinase with thrombospondin motifs 18	clinvar
PRPF8	HGNC:17340	ENSG00000174231	Q6P2Q9	Pre-mRNA-processing-splicing factor 8	clinvar
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	clinvar
CDH3	HGNC:1762	ENSG00000062038	P22223	Cadherin-3	clinvar
NMNAT1	HGNC:17877	ENSG00000173614	Q9HAN9	Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1	clinvar
WDR19	HGNC:18340	ENSG00000157796	Q8NEZ3	WD repeat-containing protein 19	clinvar
NEK9	HGNC:18591	ENSG00000119638	Q8TD19	Serine/threonine-protein kinase Nek9	clinvar
BBS7	HGNC:18758	ENSG00000138686	Q8IWZ6	BBSome complex member BBS7	clinvar
COQ8B	HGNC:19041	ENSG00000123815	Q96D53	Atypical kinase COQ8B, mitochondrial	clinvar
POMGNT1	HGNC:19139	ENSG00000085998	Q8WZA1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	clinvar
RD3	HGNC:19689	ENSG00000198570	Q7Z3Z2	Protein RD3	gwas
USP45	HGNC:20080	ENSG00000123552	Q70EL2	Ubiquitin carboxyl-terminal hydrolase 45	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF7	RING-box protein 2	Catalytic component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.
SAG	S-arrestin	Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO.
TENM4	Teneurin-4	Involved in neural development, regulating the establishment of proper connectivity within the nervous system.
DSCAML1	Cell adhesion molecule DSCAML1	Cell adhesion molecule that plays a role in neuronal self-avoidance.
SYTL4	Synaptotagmin-like protein 4	Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary.
TMED7	Transmembrane emp24 domain-containing protein 7	Potential role in vesicular protein trafficking, mainly in the early secretory pathway.
HBS1L	HBS1-like protein	GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway.
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.
GRK1	Rhodopsin kinase GRK1	Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade.
RLBP1	Retinaldehyde-binding protein 1	Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors.
RP1	Oxygen-regulated protein 1	Microtubule-associated protein regulating the stability and length of the microtubule-based axoneme of photoreceptors.
RP2	Protein XRP2	Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane.
RPE65	Retinoid isomerohydrolase	Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins.
RPGR	X-linked retinitis pigmentosa GTPase regulator	Acts as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
SLC18A2	Synaptic vesicular amine transporter	Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles.
SRC	Proto-oncogene tyrosine-protein kinase Src	Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G…
SSBP1	Single-stranded DNA-binding protein, mitochondrial	Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA).
CDKL5	Cyclin-dependent kinase-like 5	Mediates phosphorylation of MECP2.
SYN3	Synapsin-3	May be involved in the regulation of neurotransmitter release and synaptogenesis.
TCF7L2	Transcription factor 7-like 2	Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner.
TIMP3	Metalloproteinase inhibitor 3	Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metalloproteinases (MMPs).
MED12	Mediator of RNA polymerase II transcription subunit 12	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
CFAP410	Cilia- and flagella-associated protein 410	Plays a role in cilia formation and/or maintenance.
USH2A	Usherin	Involved in hearing and vision as member of the USH2 complex.
CLRN1	Clarin-1	May have a role in the excitatory ribbon synapse junctions between hair cells and cochlear ganglion cells and presumably also in analogous synapses within the retina.
BEST1	Bestrophin-1	Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+).
RPGRIP1	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	May function as scaffolding protein.
CDH23	Cadherin-23	Cadherins are calcium-dependent cell adhesion proteins.
CACNA1F	Voltage-dependent L-type calcium channel subunit alpha-1F	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
OR12D3	Olfactory receptor 12D3	Odorant receptor.
HDAC9	Histone deacetylase 9	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
PCDH18	Protocadherin-18	Potential calcium-dependent cell-adhesion protein.
CDHR1	Cadherin-related family member 1	Potential calcium-dependent cell-adhesion protein.
PRPF31	U4/U6 small nuclear ribonucleoprotein Prp31	Involved in pre-mRNA splicing as component of the spliceosome.
NBAS	NBAS subunit of NRZ tethering complex	Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER.
RP1L1	Retinitis pigmentosa 1-like 1 protein	Required for the differentiation of photoreceptor cells.
CLASP1	CLIP-associating protein 1	Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules.
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.
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.
CDH3	Cadherin-3	Cadherins are calcium-dependent cell adhesion proteins.
NMNAT1	Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1	Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP.
WDR19	WD repeat-containing protein 19	As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly.
NEK9	Serine/threonine-protein kinase Nek9	Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation.
BBS7	BBSome complex member BBS7	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
COQ8B	Atypical kinase COQ8B, mitochondrial	Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration.
POMGNT1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins.
RD3	Protein RD3	Plays a critical role in the regulation of enzymes involved in nucleotide cycle in photoreceptors.
USP45	Ubiquitin carboxyl-terminal hydrolase 45	Catalyzes the deubiquitination of SPDL1.
GPR143	G-protein coupled receptor 143	Receptor for tyrosine, L-DOPA and dopamine.
CACNA2D4	Voltage-dependent calcium channel subunit alpha-2/delta-4	The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.

Protein-family classification

Druggable: 28 · Difficult: 6 · Unknown: 41 · Druggable fraction: 0.37

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
Ion channel	5	7.4×	0.006
Kinase	6	2.2×	0.267
Protease	4	1.9×	0.496
Enzyme (other)	7	1.1×	0.894
Transporter	1	1.0×	0.894
Other/Unknown	41	1.0×	0.894
GPCR	3	1.0×	0.894
Antibody/Immunoglobulin	2	0.8×	0.907
Scaffold/PPI	3	0.7×	0.907
Transcription factor	3	0.3×	0.996

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF7	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_H2
SAG	Other/Unknown	no		Arrestin, Arrestin-like_N, Arrestin-like_C
TENM4	Other/Unknown	no		EGF, YD, CarboxyPept-like_regulatory
DSCAML1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SYTL4	Transcription factor	no		C2_dom, Synaptotagmin, Rab_BD
DHX32	Other/Unknown	no		Helicase-assoc_dom, DEAD-box_helicase_OB_fold, Helicase_ATP-bd
TMED7	Other/Unknown	no		GOLD_dom, Emp24-like, GOLD_dom_sf
HBS1L	Other/Unknown	no		T_Tr_GTP-bd_dom, EFTu-like_2, Transl_B-barrel_sf
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
GRK1	Kinase	yes	2.7.11.14	GPCR_kinase, Prot_kinase_dom, AGC-kinase_C
RLBP1	Other/Unknown	no		CRAL-TRIO_dom, CRAL/TRIO_N_dom, CRAL/TRIO_N_dom_sf
RP1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
RP2	Other/Unknown	no		CARP_motif, Tubulin-bd_cofactor_C_dom, CAP/MinC_C
RPE65	Enzyme (other)	yes	3.1.1.64	Carotenoid_Oase
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
SLC18A2	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
SRC	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
SSBP1	Other/Unknown	no		Primosome_PriB/ssb, ssDNA-bd, NA-bd_OB-fold
CDKL5	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SYN3	Other/Unknown	no		Synapsin, ATP_grasp_subdomain_1, PreATP-grasp_dom_sf
TCF7L2	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
TIMP3	Other/Unknown	no		Netrin_domain, TIMP, TIMP-like_OB-fold
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
CFAP410	Other/Unknown	no		Leu-rich_rpt, U2A’_phosphoprotein32A_C, LRR_dom_sf
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
CLRN1	Other/Unknown	no		Clarin
BEST1	Other/Unknown	no		Bestrophin, Bestrophin-like
RPGRIP1	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CACNA1F	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, Ion_trans_dom
OR12D3	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
HDAC9	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
PCDH18	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Cadherin-like_sf
CDHR1	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
PRPF31	Other/Unknown	no		Nop_dom, NOSIC, Prp31_C
NBAS	Scaffold/PPI	no		Quino_amine_DH_bsu, Sec39_domain, WD40/YVTN_repeat-like_dom_sf
RP1L1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
CLASP1	Other/Unknown	no		ARM-like, ARM-type_fold, HEAT_type_2
ADAMTS18	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
PRPF8	Other/Unknown	no		JAMM/MPN+_dom, RNaseH-like_sf, PRO8NT
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
CDH3	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
NMNAT1	Enzyme (other)	yes	2.7.7.1	Cyt_trans-like, NadD/NMNAT, Rossmann-like_a/b/a_fold
WDR19	Transcription factor	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
NEK9	Kinase	yes		Reg_chr_condens, Prot_kinase_dom, Ser/Thr_kinase_AS
BBS7	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Bardet-Biedl_syndrome_7_prot, WD40_repeat_dom_sf
COQ8B	Kinase	yes		ABC1_dom, Kinase-like_dom_sf, ADCK3_dom
POMGNT1	Enzyme (other)	yes	2.4.1.312	Glyco_trans_13, Nucleotide-diphossugar_trans, POMGNT1_PANDER-like
RD3	Other/Unknown	no		RD3
USP45	Protease	yes		Peptidase_C19_UCH, Znf_UBP, Znf_RING/FYVE/PHD

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	11
calcaneal tendon	9
secondary oocyte	8
pigmented layer of retina	7
right uterine tube	7
primordial germ cell in gonad	7
ventricular zone	7
adenohypophysis	6
right adrenal gland	5
oocyte	5
cortical plate	4
left ovary	4
islet of Langerhans	4
monocyte	4
bronchial epithelial cell	4
right adrenal gland cortex	4
buccal mucosa cell	4
right hemisphere of cerebellum	4
pituitary gland	4
left adrenal gland	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF7	292	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, right adrenal gland
SAG	106	tissue_specific	marker	nucleus accumbens, male germ line stem cell (sensu Vertebrata) in testis, left testis
TENM4	228	ubiquitous	marker	hair follicle, ganglionic eminence, lateral nuclear group of thalamus
DSCAML1	187	broad	marker	cortical plate, germinal epithelium of ovary, C1 segment of cervical spinal cord
SYTL4	230	ubiquitous	marker	left ovary, right ovary, body of uterus
DHX32	289	ubiquitous	marker	nasal cavity epithelium, esophagus squamous epithelium, tongue squamous epithelium
TMED7	291	ubiquitous	marker	choroid plexus epithelium, islet of Langerhans, calcaneal tendon
HBS1L	290	ubiquitous	marker	calcaneal tendon, muscle of leg, gastrocnemius
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm
GRK1	52	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, right lobe of thyroid gland, left lobe of thyroid gland
RLBP1	126	tissue_specific	marker	pigmented layer of retina, retina, optic choroid
RP1	103	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, male germ line stem cell (sensu Vertebrata) in testis
RP2	242	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
RPE65	92	tissue_specific	marker	pigmented layer of retina, retina, male germ line stem cell (sensu Vertebrata) in testis
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube
SLC18A2	191	broad	marker	substantia nigra pars reticulata, substantia nigra pars compacta, secondary oocyte
SRC	236	ubiquitous	marker	body of stomach, gall bladder, rectum
SSBP1	153	ubiquitous	marker	calcaneal tendon, endometrium, islet of Langerhans
CDKL5	257	ubiquitous	marker	frontal pole, Brodmann (1909) area 23, cortical plate
SYN3	176	broad	marker	primordial germ cell in gonad, cortical plate, primary visual cortex
TCF7L2	291	ubiquitous	marker	lateral nuclear group of thalamus, endothelial cell, pancreatic ductal cell
TIMP3	299	ubiquitous	marker	synovial joint, decidua, pigmented layer of retina
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
CFAP410	190	ubiquitous	marker	right uterine tube, adenohypophysis, right frontal lobe
USH2A	30	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
CLRN1	61	tissue_specific	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland
BEST1	209	ubiquitous	marker	pigmented layer of retina, lateral globus pallidus, inferior olivary complex
RPGRIP1	168	tissue_specific	marker	left testis, sperm, right testis
CDH23	161	broad	marker	ventricular zone, left ovary, right ovary
CACNA1F	143	tissue_specific	marker	parotid gland, granulocyte, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 72.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRC	11,608
PRPF8	5,582
SSBP1	4,725
CTSD	4,280
TCF7L2	3,775
RHO	3,578
PRPF31	3,427
MED12	3,322
HDAC9	3,047
TIMP3	2,921

Intra-cohort edges

A	B	Sources
ACBD5	CNGA3	biogrid_interaction, intact
ADAMTS18	KLHL22	intact
ADAMTS18	USH2A	string_interaction
ADGRV1	CDH23	string_interaction
ADGRV1	CLRN1	string_interaction
ADGRV1	USH2A	string_interaction
AHI1	COL18A1	intact
AHI1	TMEM216	string_interaction
BBS7	VPS13B	string_interaction
BEST1	EYS	string_interaction
BEST1	PRPF31	string_interaction
BEST1	RLBP1	string_interaction
BEST1	RPE65	string_interaction
BEST1	RPGR	string_interaction
CACNA1F	CACNA2D4	string_interaction
CACNA1F	RPGR	string_interaction
CDH23	CLRN1	string_interaction
CDH23	USH2A	string_interaction
CDHR1	CERKL	string_interaction
CDHR1	RPGRIP1	string_interaction
CERKL	CLRN1	string_interaction
CERKL	CNGA1	string_interaction
CERKL	CNGB1	string_interaction
CERKL	EYS	string_interaction
CERKL	PRPF31	string_interaction
CERKL	PRPF8	string_interaction
CERKL	RP1L1	string_interaction
CERKL	RPGR	string_interaction
CLN6	CTSD	string_interaction
CLN6	TPP1	string_interaction
CLRN1	USH2A	string_interaction
CNGA1	CNGB1	string_interaction
CNGA1	EYS	string_interaction
CNGA1	RHO	string_interaction
CNGA3	CNGB3	biogrid_interaction, string_interaction
CNGA3	RHO	string_interaction
CNGA3	RPE65	string_interaction
CNGA3	RPGR	string_interaction
CNGB1	EYS	string_interaction
CNGB1	RHO	string_interaction
CNGB1	RPE65	string_interaction
CNGB3	RPE65	string_interaction
CNGB3	RPGR	string_interaction
CNGB3	RPGRIP1	string_interaction
CTSD	TPP1	string_interaction
CYP4V2	EYS	string_interaction
CYP4V2	PRPF31	string_interaction
CYP4V2	RPGR	string_interaction
CYP4V2	USH2A	string_interaction
EYS	PRPF31	string_interaction

Structural data

PDB: 47 · AlphaFold-only: 28 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRPF8	Q6P2Q9	101
SRC	P12931	79
SLC18A2	Q05940	32
PRPF31	Q8WWY3	30
BEST1	O76090	19
CDH3	P22223	19
CNGA1	P29973	19
ACD	Q96AP0	19
HBS1L	Q9Y450	11
CNGB1	Q14028	11
POMGNT1	Q8WZA1	10
CNGA3	Q16281	10
CNGB3	Q9NQW8	9
COL18A1	P39060	9
CTSD	P07339	9
RNF7	Q9UBF6	7
CDH23	Q9H251	6
NMNAT1	Q9HAN9	6
SSBP1	Q04837	5
TENM4	Q6N022	4
RHO	P08100	4
RLBP1	P12271	4
WDR19	Q8NEZ3	4
KLHL22	Q53GT1	4
SYTL4	Q96C24	3
RP2	O75695	3
RPGR	Q92834	3
CDKL5	O76039	3
TCF7L2	Q9NQB0	3
MED12	Q93074	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RPE65	Q16518	95.34
BBS7	Q8IWZ6	92.99
CYP7B1	O75881	91.98
CYP4V2	Q6ZWL3	91.05
CLRN1	P58418	90.74
TMEM216	Q9P0N5	89.18
SRD5A3	Q9H8P0	89.07
DHX32	Q7L7V1	86.34
CLN6	Q9NWW5	85.86
SAG	P10523	85.44
TMED7	Q9Y3B3	84.82
OR12D3	Q9UGF7	81.77
CACNA2D4	Q7Z3S7	81.69
IFT74	Q96LB3	81.21
CERKL	Q49MI3	79.82
CDHR1	Q96JP9	78.79
COQ8B	Q96D53	77.00
NBAS	A2RRP1	74.42
GPR143	P51810	74.37
ADAMTS18	Q8TE60	73.83
CACNA1F	O60840	67.46
USP45	Q70EL2	66.28
RP1L1	Q8IWN7	38.97
RP1	P56715	37.45
USH2A	O75445
ADGRV1	Q8WXG9
EYS	Q5T1H1
VPS13B	Q7Z7G8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 456. Enrichment computed across 125 evidence-associated genes (88 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 88 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
The canonical retinoid cycle in rods (twilight vision)	6	35.4×	3e-06	RHO, RLBP1, RPE65, CYP4V2, ABCA4, MYO7A
Inactivation, recovery and regulation of the phototransduction cascade	7	25.2×	3e-06	SAG, RHO, GRK1, CNGA1, CNGB1, GUCA1A, GUCY2D
BBSome-mediated cargo-targeting to cilium	5	28.2×	1e-04	BBS7, BBS9, BBS1, BBS2, BBS5
Activation of the phototransduction cascade	4	43.3×	1e-04	SAG, RHO, CNGA1, CNGB1
Cilium Assembly	8	9.9×	1e-04	BBS7, AHI1, IQCB1, CEP290, MKS1, BBS1, BBS2, BBS5
Organelle biogenesis and maintenance	9	6.8×	5e-04	SSBP1, BBS7, AHI1, IQCB1, CEP290, MKS1, BBS1, BBS2 (+1 more)
Intraflagellar transport	5	11.4×	0.005	WDR19, IFT74, IFT140, DYNC2H1, IFT172
Hedgehog ‘off’ state	5	10.1×	0.007	WDR19, IFT140, DYNC2H1, IFT172, MKS1
Anchoring of the basal body to the plasma membrane	6	7.7×	0.007	CLASP1, AHI1, TMEM216, IQCB1, CEP290, MKS1
Visual phototransduction	4	11.8×	0.016	SAG, RPE65, ABCA4, MYO7A
Cargo trafficking to the periciliary membrane	4	11.3×	0.017	BBS7, BBS1, BBS2, BBS5
Signaling by RNF43 mutants	2	28.8×	0.078	FZD4, LRP5
Sensory Perception	5	5.4×	0.081	SAG, RPE65, CDH23, ABCA4, MYO7A
Purine ribonucleoside monophosphate biosynthesis	2	23.6×	0.101	IMPDH1, PFAS
MPS IIIC - Sanfilippo syndrome C	1	129.8×	0.185	HGSNAT
Defective SRD5A3 causes SRD5A3-CDG, KHRZ	1	129.8×	0.185	SRD5A3
Defective CYP7B1 causes SPG5A and CBAS3	1	129.8×	0.185	CYP7B1
Defective ABCC6 causes PXE	1	129.8×	0.185	ABCC6
Defective visual phototransduction due to ABCA4 loss of function	1	129.8×	0.185	ABCA4
Serotonin Neurotransmitter Release Cycle	2	14.4×	0.189	SLC18A2, SYN3
Signaling by WNT in cancer	2	13.7×	0.191	TCF7L2, LRP5
MET promotes cell motility	2	13.7×	0.191	SRC, LAMA1
Regulation of FZD by ubiquitination	2	11.8×	0.233	FZD4, LRP5
VxPx cargo-targeting to cilium	2	11.8×	0.233	RHO, CNGB1
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	64.9×	0.239	POMGNT1
Diseases associated with glycosylation precursor biosynthesis	1	64.9×	0.239	SRD5A3
Nucleotide biosynthesis	1	64.9×	0.239	IMPDH1
Defective visual phototransduction due to RDH5 loss of function	1	64.9×	0.239	RLBP1
Dopamine Neurotransmitter Release Cycle	2	11.3×	0.239	SLC18A2, SYN3
Nuclear Envelope Breakdown	2	10.4×	0.239	NEK9, NDC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 123 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
visual perception	46	29.7×	1e-53	RHO, GRK1, RLBP1, RP1, RP2, RPE65, RPGR, TIMP3 (+38 more)
photoreceptor cell maintenance	19	55.4×	1e-26	RHO, RP1, USH2A, CLRN1, CDH23, CDHR1, RP1L1, ADGRV1 (+11 more)
photoreceptor cell outer segment organization	9	77.1×	1e-13	RP1, CDHR1, RP1L1, CNGB1, AHI1, CRB1, IFT140, PCARE (+1 more)
cilium assembly	19	11.4×	9e-13	RP2, RPGR, CFAP410, WDR19, BBS7, IFT74, AHI1, TMEM216 (+11 more)
non-motile cilium assembly	11	26.0×	6e-11	RPGRIP1, BBS7, IFT74, TMEM216, CEP290, IFT140, DYNC2H1, IFT172 (+3 more)
retina development in camera-type eye	11	22.8×	2e-10	RP1, RP1L1, RD3, CNGA3, MFSD8, DRAM2, SAXO6, MERTK (+3 more)
detection of light stimulus involved in visual perception	8	42.2×	1e-09	RPE65, BEST1, CACNA1F, CACNA2D4, CNGB1, EYS, CRB1, PRPH2
sensory perception of light stimulus	5	76.1×	2e-07	USH2A, CLRN1, CDH23, ADGRV1, MYO7A
Norrin signaling pathway	4	109.6×	1e-06	TSPAN12, FZD4, LRP5, NDP
retinal blood vessel morphogenesis	4	78.3×	8e-06	FZD4, LAMA1, LRP5, NDP
monoatomic cation transmembrane transport	5	25.4×	1e-04	CNGA1, CNGA3, CNGB1, CNGB3, TRPM1
phototransduction, visible light	4	42.2×	1e-04	RHO, RP1, ABCA4, AIPL1
G protein-coupled opsin signaling pathway	3	82.2×	2e-04	SAG, RHO, GRK1
extracellular matrix-cell signaling	3	82.2×	2e-04	FZD4, LRP5, NDP
maintenance of animal organ identity	3	82.2×	2e-04	USH2A, ADGRV1, IQCB1
retina homeostasis	4	36.5×	2e-04	RPE65, CDH3, CNGB1, AIPL1
cellular response to light stimulus	4	34.2×	2e-04	RHO, RP1, CRB1, TRPM1
photoreceptor cell morphogenesis	3	68.5×	4e-04	CDHR1, TMEM216, BBS1
eye photoreceptor cell development	4	27.4×	5e-04	RPGR, CEP290, MYO7A, NR2E3
equilibrioception	3	58.7×	5e-04	CLRN1, CDH23, MYO7A
melanosome transport	4	24.9×	7e-04	BBS7, GPR143, BBS2, BBS5
retina layer formation	4	21.1×	0.001	TSPAN12, CRB1, NDP, PROM1
regulation of opsin-mediated signaling pathway	3	41.1×	0.002	GRK1, AIPL1, GUCY2D
intraciliary transport	4	18.3×	0.002	RPGR, WDPCP, IFT172, LCA5
establishment of blood-brain barrier	3	34.2×	0.003	FZD4, LRP5, NDP
phototransduction	4	16.1×	0.003	RHO, CNGB1, GUCA1A, NR2E3
determination of left/right symmetry	5	10.4×	0.004	BBS7, IFT74, IFT140, DYNC2H1, MKS1
intraciliary retrograde transport	3	27.4×	0.005	WDR19, IFT140, DYNC2H1
sensory perception of sound	7	5.7×	0.007	USH2A, CLRN1, CDH23, ADGRV1, POMGNT1, FZD4, MYO7A
protein localization to cilium	4	13.1×	0.007	IFT140, DYNC2H1, BBS9, BBS1

Therapeutics

Drugs indicated for this disease

1 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ocriplasmin	Approved (phase 4)
Bevacizumab	Phase 3 (in late-stage trials)
Povidone-Iodine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aflibercept, Finasteride, Fluocinolone Acetonide, Ranibizumab.

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 11 · Phased (≥1): 14 · Undrugged: 61

Druggability breadth: 51 of 125 evidence-associated genes (41%) 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
GRK1	RUXOLITINIB
SLC18A2	TETRABENAZINE
SRC	PONATINIB
CDKL5	FEDRATINIB
CACNA1F	BEPRIDIL
HDAC9	CELECOXIB
NEK9	MOMELOTINIB
COQ8B	FEDRATINIB
CACNA2D4	NIMODIPINE
CTSD	AMPRENAVIR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRC	103	4
CACNA1F	48	4
HDAC9	28	4
NEK9	21	4
CDKL5	14	4
GRK1	12	4
COQ8B	9	4
CTSD	8	4
SLC18A2	6	4
CACNA2D4	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RUXOLITINIB	4	GRK1
NINTEDANIB	4	GRK1, SRC
SUNITINIB	4	CACNA1F, GRK1, SRC
MIDOSTAURIN	4	GRK1, SRC
TETRABENAZINE	4	SLC18A2
KETANSERIN	4	SLC18A2
RESERPINE	4	SLC18A2
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	CDKL5, COQ8B, NEK9, SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	COQ8B, SRC
NILOTINIB	4	CACNA1F, SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
DASATINIB	4	CACNA1F, SRC
ERLOTINIB	4	COQ8B, SRC

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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

Symbol	Assays	Type breakdown
SRC	1,917	Binding:1858, Functional:43, ADMET:16
HDAC9	1,625	Binding:1612, ADMET:8, Functional:4, Toxicity:1
CTSD	352	Binding:331, ADMET:15, Toxicity:3, Functional:3
NEK9	254	Binding:254
CACNA1F	221	Binding:135, Functional:79, Toxicity:5, ADMET:2
GRK1	123	Binding:123
COQ8B	77	Binding:77
CDKL5	74	Binding:74
SLC18A2	28	Binding:26, ADMET:1, Functional:1
TCF7L2	22	Binding:22
CACNA2D4	13	Binding:13
CLASP1	10	Binding:10
PRPF8	8	Binding:8
MED12	6	Binding:6
PRPF31	6	Binding:6
NMNAT1	3	Binding:3
USP45	3	Binding:3
GPR143	3	Binding:3
CYP7B1	2	ADMET:2
DHX32	1	Binding:1
TMED7	1	Binding:1
HBS1L	1	Binding:1
RHO	1	Binding:1
RP1	1	Binding:1
SSBP1	1	Binding:1
TIMP3	1	Binding:1
CFAP410	1	Binding:1
NBAS	1	Binding:1
POMGNT1	1	Binding:1
TPP1	1	Binding:1
CLN6	1	Binding:1
NDC1	1	Binding:1
SRD5A3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GRK1	2.7.11.14	rhodopsin kinase
RPE65	3.1.1.64, 5.3.3.22	retinoid isomerohydrolase, lutein isomerase
SRC	2.7.10.2	non-specific protein-tyrosine kinase
CDKL5	2.7.11.22	cyclin-dependent kinase
HDAC9	3.5.1.98	histone deacetylase
NMNAT1	2.7.7.1, 2.7.7.18	nicotinamide-nucleotide adenylyltransferase, nicotinate-nucleotide adenylyltransferase
POMGNT1	2.4.1.312	protein O-mannose beta-1,4-N-acetylglucosaminyltransferase
TPP1	3.4.14.9	tripeptidyl-peptidase I
CYP4V2	1.14.14.79	docosahexaenoic acid omega-hydroxylase
CTSD	3.4.23.5	cathepsin D
SRD5A3	1.3.1.22, 1.3.1.94, 1.3.1.B13	3-oxo-5alpha-steroid 4-dehydrogenase (NADP+), polyprenal reductase,
CYP7B1	1.14.14.29	25/26-hydroxycholesterol 7alpha-hydroxylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GRK1	123
SRC	1,917
CACNA1F	221
HDAC9	1,625
NEK9	254
CTSD	352

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; 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)
RUXOLITINIB	4	GRK1
NINTEDANIB	4	GRK1, SRC
SUNITINIB	4	CACNA1F, GRK1, SRC
MIDOSTAURIN	4	GRK1, SRC
TETRABENAZINE	4	SLC18A2
KETANSERIN	4	SLC18A2
RESERPINE	4	SLC18A2
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	CDKL5, COQ8B, NEK9, SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	COQ8B, SRC
NILOTINIB	4	CACNA1F, SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
DASATINIB	4	CACNA1F, SRC
ERLOTINIB	4	COQ8B, SRC

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	10	GRK1, SLC18A2, SRC, CDKL5, CACNA1F, HDAC9, NEK9, COQ8B, CACNA2D4, CTSD
B	Phased (≥1) drug, not yet approved	4	TIMP3, MED12, PRPF31, PRPF8
C	Druggable family + PDB, no drug	9	DSCAML1, RHO, NMNAT1, POMGNT1, TPP1, CNGA1, CNGA3, CNGB1, CNGB3
D	Druggable family + AlphaFold only, no drug	10	RPE65, USH2A, OR12D3, ADAMTS18, ADGRV1, USP45, CERKL, CYP4V2, SRD5A3, CYP7B1
E	Difficult family or no structure, no drug	42	RNF7, SAG, TENM4, SYTL4, DHX32, TMED7, HBS1L, RLBP1, RP1, RP2 (+32 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SAG	0	GRK1
RHO	1	GRK1
EYS	0	PRPF31
RNF7	0	—
TENM4	0	—
DSCAML1	0	—
SYTL4	0	—
DHX32	1	—
TMED7	1	—
HBS1L	1	—
RLBP1	0	—
RP1	1	—
RP2	0	—
RPE65	0	—
RPGR	0	—
SSBP1	1	—
SYN3	0	—
TCF7L2	22	—
CFAP410	1	—
USH2A	0	—
CLRN1	0	—
BEST1	0	—
RPGRIP1	0	—
CDH23	0	—
OR12D3	0	—
PCDH18	0	—
CDHR1	0	—
NBAS	1	—
RP1L1	0	—
CLASP1	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	22
PHASE2	2
PHASE4	1
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT04311112	PHASE2/PHASE3	WITHDRAWN	Safety and Efficacy of Zuretinol Acetate in Subjects With Inherited Retinal Disease
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT04008121	EARLY_PHASE1	RECRUITING	Feasibility and Safety of MB-102 in Ocular Angiography as Compared to Fluorescein Sodium
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT03542734	Not specified	RECRUITING	Cognitive Impairment, Retinopathy, and Cerebrovascular Lesions in the Elderly
NCT04819893	Not specified	RECRUITING	Study of the Involvement of Fatty Acids in Retinopathy of Prematurity: Relationship Between Retinopathy of Prematurity and the Rate of Expression of Transplacental Fatty Acid Receptors.
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT06837181	Not specified	RECRUITING	Studying the Presence of CFRD Complications With Thoughtful Recruitment (SPeCTRuM)
NCT00259701	Not specified	COMPLETED	Microvascular Reactivity.
NCT00331370	Not specified	UNKNOWN	Hypertension Related Damage to the Microcirculation in South Asian: Emergence, Predictive Power and Reversibility
NCT00618644	Not specified	WITHDRAWN	Ranibizumab for Neovascularization in Sickle Cell Retinopathy
NCT00735657	Not specified	COMPLETED	Anesthesia for Pars Plana Vitrectomy (PPV) With Insulin Needle
NCT00828425	Not specified	COMPLETED	Management of Diabetes Mellitus Patients With Retinopathy
NCT00969956	Not specified	TERMINATED	Time To Complications Occurs in Diabetes
NCT01412905	Not specified	COMPLETED	Telemedicine Retinal Screening Utilizing a Mobile Medical Unit
NCT01546766	Not specified	COMPLETED	Rapid, Non-invasive, Regional Functional Imaging of the Retina. (Diabetic Retinopathy Diagnosis Device)
NCT01552993	Not specified	TERMINATED	Registration and Treatment of Pain During Eye Examination of Prematurity
NCT01815567	Not specified	COMPLETED	DETECT and Retinal Outcomes in Hypertension
NCT02321904	Not specified	COMPLETED	Corneal Confocal Microscopy to Detect Diabetic Neuropathy in Children
NCT02466607	Not specified	COMPLETED	Study of Stimulus Parameters in Flicker Electroretinogram (ERG)
NCT02558478	Not specified	UNKNOWN	Identification of New Genes Implicated in Rare Neurosensory Diseases by Whole Exome Sequencing
NCT02702973	Not specified	UNKNOWN	Characteristic Analysis of Retinopathy Associated With High Doses of Interferon α-2b Therapy
NCT03901898	Not specified	COMPLETED	Feasibility of an Intervention to Increase Diabetic Retinopathy Screening Attendance
NCT05921981	Not specified	COMPLETED	Multisensory Stimulation Versus White Noise
NCT06355219	Not specified	COMPLETED	Macrovascular and Microvascular Morbidity and Mortality After Metabolic Surgery Versus Medicines

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUORESCEIN	4	1
KETAMINE	4	1
NITROGLYCERIN	4	1
PROPOFOL	4	1
SEVOFLURANE	4	1
RELMAPIRAZIN	3	1
VATIQUINONE	3	1
CHEMBL177756	0	1