Optic atrophy

Summary

Optic atrophy (MONDO:0003608) is a disease caused by variants in OPA1 and TMEM126A, with 75 cohort genes (6 GWAS associations across 7 studies) and 10 clinical trials. The dominant Reactome pathway is Cilium Assembly (12 cohort genes). Top therapeutic interventions include deferiprone and sitagliptin.

At a glance

• Causal genes: OPA1 (GenCC Definitive), TMEM126A (GenCC Definitive)
• Cohort genes: 75
• GWAS associations: 6
• ClinVar variants: 476
• Clinical trials: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	optic atrophy
Mondo ID	MONDO:0003608
MeSH	D009896
DOID	DOID:5723
ICD-10-CM	H47.2
ICD-11	568505454
NCIT	C34863
SNOMED CT	76976005
UMLS	C0029124
MedGen	18180
Is cancer (heuristic)	no

Also known as: atrophy of optic disk

Data availability: 476 ClinVar variants · 6 GWAS associations (7 studies) · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › optic nerve disorder › optic atrophy

Related subtypes (7): optic disk drusen, optic nerve neoplasm, optic neuritis, anterior ischemic optic neuropathy, low tension glaucoma, extensive peripapillary myelinated nerve fibers, isolated optic nerve aplasia

Subtypes (3): glaucomatous atrophy of optic disk, primary optic atrophy, partial optic atrophy

Genetics & variants

GWAS landscape

6 GWAS associations across 7 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs144654840	3e-11	IRX1 - LINC02063	T	1.75
rs746386	1e-09	SERPINA12 - SERPINA4	?
rs75720470	9e-08	LYPD6B	T	0.67
rs76914338	4e-07	NEK7 - ATP6V1G3	G	0.54
rs546337899	4e-07	TMPRSS2	G	0.94
rs12405441	8e-07	LINC02781 - LINC02782	T	0.49

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477763	Verma A	2024	4,922	440,844	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477762	Verma A	2024	2,374	117,039	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480094	Verma A	2024	2,374	117,039	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477761	Verma A	2024	535	58,733	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651304	Liu TY	2025	69	56,493	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90436016	Zhou W	2018	58	401,245	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90104240	Choe EK	2022	0	0	Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	6

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	2
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	3
intron_variant	3

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs144654840	5	3938655	T>A	0.001	intergenic_variant	IRX1 - LINC02063	3e-11	Tier 4: intronic/intergenic
rs746386	14	94540589	T>C	0.05	intergenic_variant	SERPINA12 - SERPINA4	1e-09	Tier 4: intronic/intergenic
rs75720470	2	149056403	G>T	0.046	intron_variant	LYPD6B	9e-08	Tier 4: intronic/intergenic
rs76914338	1	198443151	A>G	0.073	intron_variant	NEK7 - ATP6V1G3	4e-07	Tier 4: intronic/intergenic
rs546337899	21	41502680	T>C,G	0.015	intron_variant	TMPRSS2	4e-07	Tier 4: intronic/intergenic
rs12405441	1	5027090	C>T	0.09	intergenic_variant	LINC02781 - LINC02782	8e-07	Tier 4: intronic/intergenic

ClinVar germline variants

476 retrieved; paginated sample, class counts are floors:

208 uncertain significance, 93 pathogenic, 91 conflicting classifications of pathogenicity, 34 pathogenic/likely pathogenic, 32 likely pathogenic, 8 likely benign, 8 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
973107	NM_006796.3(AFG3L2):c.[1385C>T;1858C>A]		Pathogenic	no assertion criteria provided
973111	NM_006796.3(AFG3L2):c.[1901_1902del;916A>G]		Pathogenic	no assertion criteria provided
973112	NM_006796.3(AFG3L2):c.[1814A>G;2375dup]		Pathogenic	no assertion criteria provided
236095	NM_000350.3(ABCA4):c.2875A>G (p.Thr959Ala)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7894	NM_000350.3(ABCA4):c.3113C>T (p.Ala1038Val)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99403	NM_000350.3(ABCA4):c.5714+5G>A	ABCA4	Pathogenic	reviewed by expert panel
433266	NM_001171.6(ABCC6):c.2252T>A (p.Met751Lys)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189314	NM_001098.3(ACO2):c.2328_2331del (p.Lys776fs)	ACO2	Pathogenic	criteria provided, single submitter
3250075	NM_001098.3(ACO2):c.1371-1G>C	ACO2	Pathogenic	no assertion criteria provided
3250099	NM_001098.3(ACO2):c.1360C>T (p.Gln454Ter)	ACO2	Pathogenic	no assertion criteria provided
523244	GRCh37/hg19 1q21.1-21.2(chr1:146618988-147824207)	ACP6	Pathogenic	criteria provided, single submitter
565275	NM_006796.3(AFG3L2):c.1402C>T (p.Arg468Cys)	AFG3L2	Pathogenic	criteria provided, single submitter
973104	NM_006796.3(AFG3L2):c.1394G>A (p.Arg465Lys)	AFG3L2	Pathogenic	no assertion criteria provided
973106	NM_006796.3(AFG3L2):c.1541C>T (p.Pro514Leu)	AFG3L2	Pathogenic	no assertion criteria provided
973108	NM_006796.3(AFG3L2):c.1289C>T (p.Thr430Ile)	AFG3L2	Pathogenic	no assertion criteria provided
973109	NM_006796.3(AFG3L2):c.1036C>T (p.Leu346Phe)	AFG3L2	Pathogenic	no assertion criteria provided
162088	NM_176824.3(BBS7):c.1967_1968delinsC (p.Leu656fs)	BBS7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
587382	NM_001256789.3(CACNA1F):c.4471C>T (p.Arg1491Ter)	CACNA1F	Pathogenic	criteria provided, multiple submitters, no conflicts
812245	NM_001256789.3(CACNA1F):c.4051C>T (p.Arg1351Ter)	CACNA1F	Pathogenic	criteria provided, multiple submitters, no conflicts
9481	NM_001298.3(CNGA3):c.829C>T (p.Arg277Cys)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5225	NM_019098.5(CNGB3):c.1148del (p.Thr383fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3250016	NM_207352.4(CYP4V2):c.1090+1G>C	CYP4V2	Pathogenic	no assertion criteria provided
976691	NM_032317.3(DNAJC30):c.152A>G (p.Tyr51Cys)	DNAJC30	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31204	NM_001004334.4(GPR179):c.984del (p.Ser329fs)	GPR179	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
808255	NM_001004334.4(GPR179):c.1573C>T (p.Arg525Ter)	GPR179	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98582	NM_000180.4(GUCY2D):c.2944+1del	GUCY2D	Pathogenic	reviewed by expert panel
183353	NM_194279.4(ISCA2):c.229G>A (p.Gly77Ser)	ISCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3250032	NC_000003.12:g.(?193593498)(193694763_?)del	LOC126806913	Pathogenic	criteria provided, single submitter
95713	NM_130837.3(OPA1):c.1834C>T (p.Arg612Ter)	LOC126806913	Pathogenic	criteria provided, multiple submitters, no conflicts
374878	NM_016011.5(MECR):c.695G>A (p.Gly232Glu)	MECR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 38 · Orphanet: 145 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MED12	Definitive	Autosomal dominant	autosomal dominant optic atrophy, classic form	21
OPA1	Definitive	Autosomal dominant	autosomal dominant optic atrophy, classic form	11
TMEM126A	Definitive	Autosomal recessive	optic atrophy	5
NDUFA7	Limited	Autosomal recessive	optic atrophy

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
TMEM126A	Orphanet:227976	Autosomal recessive optic atrophy, OPA7 type
OPA1	Orphanet:1215	Autosomal dominant optic atrophy plus syndrome
OPA1	Orphanet:1239	Behr syndrome
OPA1	Orphanet:98673	Autosomal dominant optic atrophy, classic form
RGS9	Orphanet:75374	Bradyopsia
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa
RLBP1	Orphanet:227796	Fundus albipunctatus
RLBP1	Orphanet:52427	Retinitis punctata albescens
RLBP1	Orphanet:791	Retinitis pigmentosa
RLBP1	Orphanet:85128	Bothnia retinal dystrophy
ROM1	Orphanet:791	Retinitis pigmentosa
RP9	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
CWC27	Orphanet:166035	Brachydactyly-short stature-retinitis pigmentosa syndrome
SEMA4A	Orphanet:1872	Cone rod dystrophy
SEMA4A	Orphanet:440437	Familial colorectal cancer Type X
SEMA4A	Orphanet:791	Retinitis pigmentosa
SEMA6B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SNAP25	Orphanet:98914	Presynaptic congenital myasthenic syndromes
SPG7	Orphanet:35689	Primary lateral sclerosis
SPG7	Orphanet:99013	Spastic paraplegia type 7
SSBP1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
PLK4	Orphanet:2518	Autosomal recessive chorioretinopathy-microcephaly syndrome
PLK4	Orphanet:808	Seckel syndrome
ACO2	Orphanet:313850	Infantile cerebellar-retinal degeneration
ACO2	Orphanet:98676	Autosomal recessive isolated optic atrophy
TTPA	Orphanet:96	Ataxia with vitamin E deficiency
USH1C	Orphanet:231169	Usher syndrome type 1
USH1C	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
USH2A	Orphanet:231178	Usher syndrome type 2
USH2A	Orphanet:791	Retinitis pigmentosa
CLRN1	Orphanet:231183	Usher syndrome type 3
CLRN1	Orphanet:791	Retinitis pigmentosa
WFS1	Orphanet:3463	Wolfram syndrome
WFS1	Orphanet:411590	Wolfram-like syndrome
WFS1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
WFS1	Orphanet:98991	Early-onset nuclear cataract
SCAPER	Orphanet:110	Bardet-Biedl syndrome
SCAPER	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	gencc,clinvar
TMEM126A	HGNC:25382	ENSG00000171202	Q9H061	Transmembrane protein 126A	gencc,clinvar
OPA1	HGNC:8140	ENSG00000198836	O60313	Dynamin-like GTPase OPA1, mitochondrial	gencc,clinvar
NDUFA7	HGNC:7691	ENSG00000267855	O95182	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7	gencc
RGS9	HGNC:10004	ENSG00000108370	O75916	Regulator of G-protein signaling 9	clinvar
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
RLBP1	HGNC:10024	ENSG00000140522	P12271	Retinaldehyde-binding protein 1	clinvar
ROM1	HGNC:10254	ENSG00000149489	Q03395	Rod outer segment membrane protein 1	clinvar
RP9	HGNC:10288	ENSG00000164610	Q8TA86	Retinitis pigmentosa 9 protein	clinvar
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	clinvar
CWC27	HGNC:10664	ENSG00000153015	Q6UX04	Spliceosome-associated protein CWC27 homolog	clinvar
SEMA4A	HGNC:10729	ENSG00000196189	Q9H3S1	Semaphorin-4A	clinvar
SEMA6B	HGNC:10739	ENSG00000167680	Q9H3T3	Semaphorin-6B	clinvar
SLC24A1	HGNC:10975	ENSG00000074621	O60721	Sodium/potassium/calcium exchanger 1	clinvar
SNAP25	HGNC:11132	ENSG00000132639	P60880	Synaptosomal-associated protein 25	clinvar
SPG7	HGNC:11237	ENSG00000197912	Q9UQ90	Mitochondrial inner membrane m-AAA protease component paraplegin	clinvar
SSBP1	HGNC:11317	ENSG00000106028	Q04837	Single-stranded DNA-binding protein, mitochondrial	clinvar
PLK4	HGNC:11397	ENSG00000142731	O00444	Serine/threonine-protein kinase PLK4	clinvar
ACO2	HGNC:118	ENSG00000100412	Q99798	Aconitate hydratase, mitochondrial	clinvar
TTPA	HGNC:12404	ENSG00000137561	P49638	Alpha-tocopherol transfer protein	clinvar
USH1C	HGNC:12597	ENSG00000006611	Q9Y6N9	Harmonin	clinvar
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	clinvar
CLRN1	HGNC:12605	ENSG00000163646	P58418	Clarin-1	clinvar
WFS1	HGNC:12762	ENSG00000109501	O76024	Wolframin	clinvar
SCAPER	HGNC:13081	ENSG00000140386	Q9BY12	S phase cyclin A-associated protein in the endoplasmic reticulum	clinvar
ARL6	HGNC:13210	ENSG00000113966	Q9H0F7	ADP-ribosylation factor-like protein 6	clinvar
ESPN	HGNC:13281	ENSG00000187017	B1AK53	Espin	clinvar
RPGRIP1	HGNC:13436	ENSG00000092200	Q96KN7	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	clinvar
ABITRAM	HGNC:1364	ENSG00000119328	Q9NX38	Protein Abitram	clinvar
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	clinvar
ADGRA3	HGNC:13839	ENSG00000152990	Q8IWK6	Adhesion G protein-coupled receptor A3	clinvar
CABP4	HGNC:1386	ENSG00000175544	P57796	Calcium-binding protein 4	clinvar
CACNA1F	HGNC:1393	ENSG00000102001	O60840	Voltage-dependent L-type calcium channel subunit alpha-1F	clinvar
PIGQ	HGNC:14135	ENSG00000007541	Q9BRB3	Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q	clinvar
C1QTNF5	HGNC:14344	ENSG00000223953	Q9BXJ0	Complement C1q tumor necrosis factor-related protein 5	clinvar
ELOVL1	HGNC:14418	ENSG00000066322	Q9BW60	Very long chain fatty acid elongase 1	clinvar
CDHR1	HGNC:14550	ENSG00000148600	Q96JP9	Cadherin-related family member 1	clinvar
PCDH15	HGNC:14674	ENSG00000150275	Q96QU1	Protocadherin-15	clinvar
GPHN	HGNC:15465	ENSG00000171723	Q9NQX3	Gephyrin	clinvar
NBAS	HGNC:15625	ENSG00000151779	A2RRP1	NBAS subunit of NRZ tethering complex	clinvar
ABHD12	HGNC:15868	ENSG00000100997	Q8N2K0	Lysophosphatidylserine lipase ABHD12	clinvar
PANK2	HGNC:15894	ENSG00000125779	Q9BZ23	Pantothenate kinase 2, mitochondrial	clinvar
RP1L1	HGNC:15946	ENSG00000183638	Q8IWN7	Retinitis pigmentosa 1-like 1 protein	clinvar
PNPLA6	HGNC:16268	ENSG00000032444	Q8IY17	Patatin-like phospholipase domain-containing protein 6	clinvar
USH1G	HGNC:16356	ENSG00000182040	Q495M9	pre-mRNA splicing regulator USH1G	clinvar
WHRN	HGNC:16361	ENSG00000095397	Q9P202	Whirlin	clinvar
DNAJC30	HGNC:16410	ENSG00000176410	Q96LL9	DnaJ homolog subfamily C member 30, mitochondrial	clinvar
TUBGCP4	HGNC:16691	ENSG00000137822	Q9UGJ1	Gamma-tubulin complex component 4	clinvar
ZNF423	HGNC:16762	ENSG00000102935	Q2M1K9	Zinc finger protein 423	clinvar
MFN2	HGNC:16877	ENSG00000116688	O95140	Mitofusin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
TMEM126A	Transmembrane protein 126A	Protein required for the cotranslational protein quality control in the inner membrane of the mitochondria.
OPA1	Dynamin-like GTPase OPA1, mitochondrial	Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain function.
NDUFA7	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
RGS9	Regulator of G-protein signaling 9	Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.
RLBP1	Retinaldehyde-binding protein 1	Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors.
ROM1	Rod outer segment membrane protein 1	Plays a role in rod outer segment (ROS) morphogenesis.
RP9	Retinitis pigmentosa 9 protein	Is thought to be a target protein for the PIM1 kinase.
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.
CWC27	Spliceosome-associated protein CWC27 homolog	As part of the spliceosome, plays a role in pre-mRNA splicing.
SEMA4A	Semaphorin-4A	Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling.
SEMA6B	Semaphorin-6B	Functions as a cell surface repellent for mossy fibers of developing neurons in the hippocampus where it plays a role in axon guidance.
SLC24A1	Sodium/potassium/calcium exchanger 1	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
SNAP25	Synaptosomal-associated protein 25	t-SNARE involved in the molecular regulation of neurotransmitter release.
SPG7	Mitochondrial inner membrane m-AAA protease component paraplegin	Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development.
SSBP1	Single-stranded DNA-binding protein, mitochondrial	Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA).
PLK4	Serine/threonine-protein kinase PLK4	Serine/threonine-protein kinase that plays a central role in centriole duplication.
ACO2	Aconitate hydratase, mitochondrial	Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
TTPA	Alpha-tocopherol transfer protein	Binds alpha-tocopherol, enhances its transfer between separate membranes, and stimulates its release from liver cells.
USH1C	Harmonin	Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells.
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.
WFS1	Wolframin	Participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca(2+) store.
SCAPER	S phase cyclin A-associated protein in the endoplasmic reticulum	CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm.
ARL6	ADP-ribosylation factor-like protein 6	Involved in membrane protein trafficking at the base of the ciliary organelle.
ESPN	Espin	Multifunctional actin-bundling protein.
RPGRIP1	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	May function as scaffolding protein.
ABITRAM	Protein Abitram	Actin-binding protein that regulates actin polymerization, filopodia dynamics and increases the branching of proximal dendrites of developing neurons.
CDH23	Cadherin-23	Cadherins are calcium-dependent cell adhesion proteins.
ADGRA3	Adhesion G protein-coupled receptor A3	Orphan receptor that may have a role in planar cell polarity pathway.
CABP4	Calcium-binding protein 4	Involved in normal synaptic function through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals and in auditory transmission.
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…
PIGQ	Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q	Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI bi…
ELOVL1	Very long chain fatty acid elongase 1	Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.
CDHR1	Cadherin-related family member 1	Potential calcium-dependent cell-adhesion protein.
PCDH15	Protocadherin-15	Calcium-dependent cell-adhesion protein.
GPHN	Gephyrin	Microtubule-associated protein involved in membrane protein-cytoskeleton interactions.
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.
ABHD12	Lysophosphatidylserine lipase ABHD12	Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes.
PANK2	Pantothenate kinase 2, mitochondrial	Mitochondrial isoform that catalyzes the phosphorylation of pantothenate to generate 4’-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.
RP1L1	Retinitis pigmentosa 1-like 1 protein	Required for the differentiation of photoreceptor cells.
PNPLA6	Patatin-like phospholipase domain-containing protein 6	Phospholipase B that deacylates intracellular phosphatidylcholine (PtdCho), generating glycerophosphocholine (GroPtdCho).
USH1G	pre-mRNA splicing regulator USH1G	Plays a role in pre-mRNA splicing by regulating the release and transfer of U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complexes from their assembly site in Cajal bodies to nuclear speckles, thereby contributing to the assemb…
WHRN	Whirlin	Involved in hearing and vision as member of the USH2 complex.
DNAJC30	DnaJ homolog subfamily C member 30, mitochondrial	Mitochondrial protein enriched in neurons that acts as a regulator of mitochondrial respiration.
TUBGCP4	Gamma-tubulin complex component 4	Component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation.
ZNF423	Zinc finger protein 423	Transcription factor that can both act as an activator or a repressor depending on the context.
MFN2	Mitofusin-2	Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion.
ARHGEF18	Rho guanine nucleotide exchange factor 18	Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases.

Protein-family classification

Druggable: 20 · Difficult: 14 · Unknown: 41 · 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
Ion channel	4	6.0×	0.042
Scaffold/PPI	9	2.1×	0.129
Protease	3	1.5×	0.757
Enzyme (other)	8	1.3×	0.757
Other/Unknown	41	1.0×	0.939
GPCR	3	1.0×	0.939
Transcription factor	5	0.6×	0.958
Antibody/Immunoglobulin	1	0.4×	0.958
Kinase	1	0.4×	0.958

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
TMEM126A	Other/Unknown	no		TMEM126
OPA1	Enzyme (other)	yes	3.6.5.5	Dynamin_GTPase, Dynamin, P-loop_NTPase
NDUFA7	Other/Unknown	no		NDUA7
RGS9	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
RLBP1	Other/Unknown	no		CRAL-TRIO_dom, CRAL/TRIO_N_dom, CRAL/TRIO_N_dom_sf
ROM1	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS
RP9	Other/Unknown	no		PAP-1
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
CWC27	Enzyme (other)	yes	5.2.1.8	Cyclophilin-type_PPIase_dom, Cyclophilin-type_PPIase_CS, Cyclophilin-like_dom_sf
SEMA4A	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_sf
SEMA6B	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_sf
SLC24A1	Other/Unknown	no		K/Na/Ca-exchanger, SLC24A1, NaCa_Exmemb
SNAP25	Other/Unknown	no		T_SNARE_dom, SNAP-25_dom, SNAP-25_N_SNARE_chord
SPG7	Protease	yes	3.4.24.B18	Peptidase_M41, AAA+_ATPase, ATPase_AAA_core
SSBP1	Other/Unknown	no		Primosome_PriB/ssb, ssDNA-bd, NA-bd_OB-fold
PLK4	Kinase	yes	2.7.11.21	Prot_kinase_dom, POLO_box_dom, Tyr_kinase_AS
ACO2	Enzyme (other)	yes	4.2.1.3	AconitaseA/IPMdHydase_ssu_swvl, Acoase/IPM_deHydtase_lsu_aba, Aconitase_mito-like
TTPA	Other/Unknown	no		CRAL-TRIO_dom, CRAL/TRIO_N_dom, CRAL/TRIO_N_dom_sf
USH1C	Scaffold/PPI	no		PDZ, Harmonin_N, PDZ_sf
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
CLRN1	Other/Unknown	no		Clarin
WFS1	Other/Unknown	no		TPR-like_helical_dom_sf, Wolframin, Wolframin_fam
SCAPER	Transcription factor	no		Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type, SCAPER_N
ARL6	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF
ESPN	Scaffold/PPI	no		Ankyrin_rpt, WH2_dom, Ankyrin_rpt-contain_sf
RPGRIP1	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
ABITRAM	Other/Unknown	no		Single_hybrid_motif, GCV_H/Fam206, Abitram
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
ADGRA3	GPCR	yes		GPS, Cys-rich_flank_reg_C, GPCR_2_secretin-like
CABP4	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
CACNA1F	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, Ion_trans_dom
PIGQ	Enzyme (other)	yes	2.4.1.198	PigQ/GPI1
C1QTNF5	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
ELOVL1	Other/Unknown	no		ELO_fam, ELO_CS, ELOVL1
CDHR1	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
PCDH15	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
GPHN	Other/Unknown	no		MoaB/Mog_dom, MoeA_linker/N, MoeA_C_domain_IV
NBAS	Scaffold/PPI	no		Quino_amine_DH_bsu, Sec39_domain, WD40/YVTN_repeat-like_dom_sf
ABHD12	Other/Unknown	no		AB_hydrolase_1, AB_hydrolase_fold
PANK2	Enzyme (other)	yes	2.7.1.33	Type_II_PanK, ATPase_NBD
RP1L1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
PNPLA6	Other/Unknown	no		cNMP-bd_dom, LysoPLipase_patatin_CS, PNPLA_dom
USH1G	Scaffold/PPI	no		SAM, Ankyrin_rpt, SAM/pointed_sf
WHRN	Scaffold/PPI	no		PDZ, Whirlin_HN-like_dom2, PDZ_sf
DNAJC30	Other/Unknown	no		DnaJ_domain, J_dom_sf, Mito_ATP_Synthase-Asso
TUBGCP4	Other/Unknown	no		GCP, GCP_C, GCP_N
ZNF423	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
MFN2	Other/Unknown	no		Fzo/mitofusin_HR2, Mitofusin_fam, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	7
apex of heart	7
primordial germ cell in gonad	7
right uterine tube	7
calcaneal tendon	6
male germ line stem cell (sensu Vertebrata) in testis	6
ventricular zone	6
adrenal tissue	5
C1 segment of cervical spinal cord	5
sperm	5
sural nerve	5
right lobe of liver	5
secondary oocyte	5
right adrenal gland	4
right adrenal gland cortex	4
left ventricle myocardium	4
oocyte	4
bronchial epithelial cell	4
left testis	4
right testis	4

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
TMEM126A	257	ubiquitous	marker	left ventricle myocardium, tibialis anterior, deltoid
OPA1	288	ubiquitous	marker	adrenal tissue, calcaneal tendon, endothelial cell
NDUFA7	164	ubiquitous	marker	hindlimb stylopod muscle, apex of heart, gastrocnemius
RGS9	178	ubiquitous	marker	putamen, caudate nucleus, islet of Langerhans
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm
RLBP1	126	tissue_specific	marker	pigmented layer of retina, retina, optic choroid
ROM1	201	broad	marker	primordial germ cell in gonad, C1 segment of cervical spinal cord, spinal cord
RP9	256	ubiquitous	marker	oocyte, left ventricle myocardium, hindlimb stylopod muscle
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube
CWC27	253	ubiquitous	marker	tendon of biceps brachii, medial globus pallidus, globus pallidus
SEMA4A	219	broad	marker	monocyte, mononuclear cell, leukocyte
SEMA6B	177	ubiquitous	marker	right frontal lobe, anterior cingulate cortex, cingulate cortex
SLC24A1	220	ubiquitous	marker	endothelial cell, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
SNAP25	220	broad	marker	pons, cerebellar cortex, cerebellum
SPG7	302	ubiquitous	marker	primordial germ cell in gonad, sural nerve, left lobe of thyroid gland
SSBP1	153	ubiquitous	marker	calcaneal tendon, endometrium, islet of Langerhans
PLK4	201	ubiquitous	marker	ventricular zone, ganglionic eminence, primordial germ cell in gonad
ACO2	291	ubiquitous	marker	heart right ventricle, apex of heart, left ventricle myocardium
TTPA	135	broad	yes	right lobe of liver, liver, buccal mucosa cell
USH1C	203	broad	marker	mucosa of transverse colon, C1 segment of cervical spinal cord, rectum
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
WFS1	280	ubiquitous	marker	right ovary, left ovary, body of uterus
SCAPER	282	ubiquitous	marker	cortical plate, male germ line stem cell (sensu Vertebrata) in testis, sural nerve
ARL6	228	ubiquitous	marker	oviduct epithelium, Brodmann (1909) area 23, endothelial cell
ESPN	184	broad	marker	right testis, left testis, right uterine tube
RPGRIP1	168	tissue_specific	marker	left testis, sperm, right testis
ABITRAM	287	ubiquitous	marker	bronchial epithelial cell, tongue squamous epithelium, epithelium of bronchus
CDH23	161	broad	marker	ventricular zone, left ovary, right ovary

Protein interactions among cohort

Intra-cohort edges: 82.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACO2	4,776
SSBP1	4,725
SPG7	3,970
MFN2	3,853
PLK4	3,694
PMPCA	3,679
RHO	3,578
WFS1	3,409
MED12	3,322
CWC27	2,984

Intra-cohort edges

A	B	Sources
ABHD12	ZNF408	string_interaction
ACO2	DNAJC30	intact
ACO2	ISCA2	string_interaction
ADGRA3	ADGRV1	string_interaction
ADGRV1	CDH23	string_interaction
ADGRV1	CLRN1	string_interaction
ADGRV1	PCDH15	string_interaction
ADGRV1	USH1G	string_interaction
ADGRV1	USH2A	string_interaction
ADGRV1	WHRN	string_interaction
ARL6	BBS7	intact, string_interaction
BBS7	INPP5E	string_interaction
C10orf105	CDH23	string_interaction
CABP4	CACNA1F	biogrid_interaction, string_interaction
CABP4	CACNA2D4	string_interaction
CABP4	SLC24A1	string_interaction
CACNA1F	CACNA2D4	string_interaction
CACNA1F	RPGR	string_interaction
CACNA2D4	KCNV2	string_interaction
CDH23	CLRN1	string_interaction
CDH23	ESPN	string_interaction
CDH23	PCDH15	string_interaction
CDH23	USH1C	biogrid_interaction, intact
CDH23	USH1G	string_interaction
CDH23	USH2A	string_interaction
CDH23	WHRN	string_interaction
CDHR1	KCNV2	string_interaction
CDHR1	RPGRIP1	string_interaction
CDHR1	SEMA4A	string_interaction
CEP250	CLRN1	string_interaction
CEP250	USH1G	string_interaction
CLRN1	PCDH15	string_interaction
CLRN1	USH1G	string_interaction
CLRN1	USH2A	string_interaction
CLRN1	WHRN	string_interaction
CNGA1	RHO	string_interaction
CNGA1	ROM1	string_interaction
CNGA1	SLC24A1	biogrid_interaction, string_interaction
CNGA3	KCNV2	string_interaction
CNGA3	RHO	string_interaction
CNGA3	RPGR	string_interaction
CNGA3	SLC24A1	string_interaction
DNAJC30	NDUFA7	biogrid_interaction, intact
ESPN	WHRN	string_interaction
INPP5E	RPGR	intact
INVS	NPHP4	biogrid_interaction, intact, string_interaction
KCNV2	RPGRIP1	string_interaction
MFN2	OPA1	string_interaction
NBAS	SCAPER	string_interaction
NDUFA7	TTPA	intact

Structural data

PDB: 39 · AlphaFold-only: 36 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUBGCP6	Q96RT7	30
TUBGCP4	Q9UGJ1	28
PLK4	O00444	19
CNGA1	P29973	19
SNAP25	P60880	14
OPA1	O60313	11
USH1C	Q9Y6N9	11
POMGNT1	Q8WZA1	10
CNGA3	Q16281	10
CWC27	Q6UX04	9
PCDH15	Q96QU1	8
NDUFA7	O95182	7
TTPA	P49638	6
CDH23	Q9H251	6
SSBP1	Q04837	5
WHRN	Q9P202	5
RHO	P08100	4
RLBP1	P12271	4
WDR19	Q8NEZ3	4
MECR	Q9BV79	4
MED12	Q93074	3
RPGR	Q92834	3
USH1G	Q495M9	3
MFN2	O95140	3
TRNT1	Q96Q11	3
SCAPER	Q9BY12	2
C1QTNF5	Q9BXJ0	2
ROM1	Q03395	1
SPG7	Q9UQ90	1
ARL6	Q9H0F7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACO2	Q99798	95.44
BBS7	Q8IWZ6	92.99
CLRN1	P58418	90.74
ELOVL1	Q9BW60	90.46
TMEM126A	Q9H061	89.75
PMPCA	Q10713	88.46
ABHD12	Q8N2K0	85.60
SEMA4A	Q9H3S1	85.05
CACNA2D4	Q7Z3S7	81.69
IFT74	Q96LB3	81.21
ABITRAM	Q9NX38	80.21
RP9	Q8TA86	78.99
CDHR1	Q96JP9	78.79
ISCA2	Q86U28	77.98
KCNV2	Q8TDN2	75.55
SEMA6B	Q9H3T3	74.81
NBAS	A2RRP1	74.42
RGS9	O75916	74.35
WFS1	O76024	73.85
NPHP4	O75161	72.44
INVS	Q9Y283	70.76
ADGRA3	Q8IWK6	70.20
PNPLA6	Q8IY17	69.75
ESPN	B1AK53	68.76
CACNA1F	O60840	67.46
USP45	Q70EL2	66.28
CABP4	P57796	65.01
PIGQ	Q9BRB3	64.70
C10orf105	Q8TEF2	63.46
ARHGEF18	Q6ZSZ5	62.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 306. Enrichment computed across 164 evidence-associated genes (114 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 114 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cilium Assembly	12	11.4×	1e-07	ARL6, BBS7, INPP5E, AHI1, CEP78, BBS10, SCLT1, CEP290 (+4 more)
Anchoring of the basal body to the plasma membrane	11	10.9×	7e-07	PLK4, CEP250, NPHP4, AHI1, CEP78, SCLT1, CEP290, RPGRIP1L (+3 more)
Organelle biogenesis and maintenance	13	7.5×	2e-06	SSBP1, ARL6, BBS7, INPP5E, AHI1, CEP78, BBS10, SCLT1 (+5 more)
The canonical retinoid cycle in rods (twilight vision)	6	27.3×	4e-06	RHO, RLBP1, CYP4V2, ABCA4, MYO7A, RBP3
Sensory processing of sound by inner hair cells of the cochlea	8	11.4×	3e-05	SNAP25, USH1C, ESPN, CDH23, PCDH15, USH1G, WHRN, MYO7A
Mitochondrial protein degradation	9	9.0×	3e-05	OPA1, SPG7, SSBP1, ACO2, PMPCA, AFG3L2, MT-CO1, MT-ND1 (+1 more)
Sensory processing of sound by outer hair cells of the cochlea	7	12.5×	6e-05	USH1C, ESPN, CDH23, PCDH15, USH1G, WHRN, MYO7A
Activation of the phototransduction cascade	4	33.4×	2e-04	RHO, SLC24A1, CNGA1, CNGB1
Intraflagellar transport	6	10.5×	6e-04	WDR19, IFT74, IFT140, DYNC2H1, IFT172, KIF3B
Recruitment of mitotic centrosome proteins and complexes	7	8.3×	6e-04	PLK4, TUBGCP4, TUBGCP6, CEP250, CEP78, CEP290, ALMS1
Inactivation, recovery and regulation of the phototransduction cascade	5	13.9×	7e-04	RGS9, RHO, CNGA1, CNGB1, GUCY2D
Hedgehog ‘off’ state	6	9.4×	0.001	WDR19, IFT140, RPGRIP1L, DYNC2H1, IFT172, MKS1
Recruitment of NuMA to mitotic centrosomes	7	7.2×	0.001	PLK4, TUBGCP4, TUBGCP6, CEP250, CEP78, CEP290, ALMS1
Complex I biogenesis	6	8.7×	0.001	TMEM126A, MT-ND1, MT-ND4, MT-ND6, NDUFA7, NDUFS2
BBSome-mediated cargo-targeting to cilium	4	17.4×	0.001	ARL6, BBS7, BBS10, BBS9
Respiratory electron transport	7	5.8×	0.004	TMEM126A, MT-CO1, MT-ND1, MT-ND4, MT-ND6, NDUFA7, NDUFS2
Processing of SMDT1	3	16.7×	0.012	SPG7, PMPCA, AFG3L2
Loss of Nlp from mitotic centrosomes	5	7.0×	0.012	PLK4, CEP250, CEP78, CEP290, ALMS1
Loss of proteins required for interphase microtubule organization from the centrosome	5	7.0×	0.012	PLK4, CEP250, CEP78, CEP290, ALMS1
AURKA Activation by TPX2	5	6.7×	0.014	PLK4, CEP250, CEP78, CEP290, ALMS1
Mitochondrial calcium ion transport	3	14.3×	0.016	SPG7, PMPCA, AFG3L2
Cargo trafficking to the periciliary membrane	4	8.7×	0.016	ARL6, BBS7, INPP5E, BBS10
The retinoid cycle in cones (daylight vision)	2	28.6×	0.026	RLBP1, RBP3
Regulation of PLK1 Activity at G2/M Transition	5	5.6×	0.026	PLK4, CEP250, CEP78, CEP290, ALMS1
Citric acid cycle (TCA cycle)	3	11.1×	0.029	ACO2, ISCA2, IDH3B
Opsins	2	22.3×	0.038	RHO, RGR
Signaling by RNF43 mutants	2	22.3×	0.038	FZD4, LRP5
Sensory processing of sound	3	8.1×	0.064	SNAP25, CDH23, MYO7A
Sensory Perception	5	4.2×	0.073	SLC24A1, SNAP25, CDH23, ABCA4, MYO7A
Defective SLC24A1 causes congenital stationary night blindness 1D (CSNB1D)	1	100.2×	0.082	SLC24A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 161 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	44	21.7×	4e-44	OPA1, RGS9, RHO, RLBP1, ROM1, RPGR, SLC24A1, USH2A (+36 more)
photoreceptor cell maintenance	20	44.5×	4e-26	RHO, USH1C, USH2A, CLRN1, CDH23, CDHR1, PCDH15, RP1L1 (+12 more)
photoreceptor cell outer segment organization	11	72.0×	5e-17	ROM1, CDHR1, RP1L1, NPHP4, CNGB1, AHI1, TOPORS, CRB1 (+3 more)
sensory perception of light stimulus	9	104.7×	1e-16	USH1C, USH2A, CLRN1, CDH23, PCDH15, USH1G, WHRN, ADGRV1 (+1 more)
cilium assembly	21	9.6×	9e-13	RPGR, PLK4, ARL6, WDR19, CEP250, BBS7, IFT74, INPP5E (+13 more)
non-motile cilium assembly	13	23.5×	1e-12	RPGRIP1, CEP250, BBS7, IFT74, BBS10, CEP290, IFT140, RPGRIP1L (+5 more)
detection of light stimulus involved in visual perception	10	40.3×	3e-12	ROM1, CACNA1F, CEP250, CACNA2D4, CNGB1, EYS, CRB1, REEP6 (+2 more)
equilibrioception	6	89.7×	5e-10	USH1C, CLRN1, CDH23, PCDH15, USH1G, MYO7A
retina development in camera-type eye	11	17.4×	3e-09	SCAPER, RP1L1, NPHP4, TTLL5, CNGA3, ZNF513, MFSD8, GRM6 (+3 more)
determination of left/right symmetry	10	15.9×	6e-08	ARL6, BBS7, IFT74, IFT140, RPGRIP1L, CC2D2A, DYNC2H1, KIF3B (+2 more)
sensory perception of sound	14	8.8×	6e-08	USH1C, USH2A, CLRN1, WFS1, ESPN, CDH23, PCDH15, USH1G (+6 more)
aerobic respiration	8	12.3×	2e-05	PANK2, MFN2, MT-CO1, MT-ND1, MT-ND4, MT-ND6, NDUFA7, NDUFS2
eye photoreceptor cell development	5	26.2×	7e-05	RPGR, POC5, CEP290, MYO7A, NR2E3
inner ear receptor cell stereocilium organization	5	26.2×	7e-05	USH1C, USH1G, WHRN, ADGRV1, MKS1
mitochondrial respiratory chain complex I assembly	6	15.3×	1e-04	TMEM126A, MIEF1, MT-ND1, MT-ND4, MT-ND6, NDUFS2
protein localization to cilium	6	14.9×	2e-04	ARL6, ZNF423, CEP78, IFT140, DYNC2H1, BBS9
retina layer formation	5	20.1×	2e-04	ARL6, TSPAN12, TOPORS, CRB1, PROM1
regulation of smoothened signaling pathway	5	19.4×	2e-04	ARL6, IFT140, RPGRIP1L, MKS1, OTX2
monoatomic cation transmembrane transport	5	19.4×	2e-04	CNGA1, CNGA3, CNGB1, CNGB3, TRPM1
maintenance of animal organ identity	3	62.8×	3e-04	USH2A, ADGRV1, NPHP3
inner ear receptor cell differentiation	3	62.8×	3e-04	USH2A, WHRN, ADGRV1
Norrin signaling pathway	3	62.8×	3e-04	TSPAN12, FZD4, LRP5
intraciliary transport	5	17.4×	3e-04	RPGR, WDPCP, IFT172, LCA5, KIF3B
cellular response to light stimulus	4	26.2×	5e-04	RHO, CRB1, TRPM1, RGR
phototransduction	5	15.4×	6e-04	RHO, CABP4, CNGB1, NR2E3, RGR
kidney development	8	7.0×	7e-04	WFS1, INVS, WDPCP, CEP290, RPGRIP1L, CC2D2A, DYNC2H1, NPHP3
retinal blood vessel morphogenesis	3	44.9×	9e-04	FZD4, LAMA1, LRP5
protein localization to photoreceptor outer segment	3	44.9×	9e-04	ROM1, SPATA7, PCARE
establishment of protein localization	5	13.4×	0.001	USH2A, GPHN, WHRN, ADGRV1, WDPCP
auditory receptor cell stereocilium organization	4	20.9×	0.001	CLRN1, CDH23, WHRN, MYO7A

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 7 · Undrugged: 68

Druggability breadth: 53 of 164 evidence-associated genes (32%) 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
OPA1	MOMELOTINIB
PLK4	MOMELOTINIB
CACNA1F	BEPRIDIL
ABHD12	ORLISTAT
CACNA2D4	NIMODIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLK4	65	4
CACNA1F	48	4
OPA1	2	4
ABHD12	2	4
CACNA2D4	2	4
MED12	1	2
CWC27	1	2
TMEM126A	0	0
NDUFA7	0	0
RGS9	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	OPA1, PLK4
FEDRATINIB	4	PLK4
AXITINIB	4	PLK4
SORAFENIB	4	PLK4
RUXOLITINIB	4	PLK4
ENTRECTINIB	4	PLK4
DABRAFENIB	4	PLK4
FOSTAMATINIB	4	PLK4
CERITINIB	4	PLK4
VANDETANIB	4	PLK4
GILTERITINIB	4	PLK4
PAZOPANIB	4	PLK4
NINTEDANIB	4	PLK4
SUNITINIB	4	CACNA1F, PLK4
DASATINIB	4	CACNA1F, PLK4
ERLOTINIB	4	PLK4
CRIZOTINIB	4	PLK4
MIDOSTAURIN	4	PLK4
IMATINIB	4	PLK4
BEPRIDIL	4	CACNA1F
IMIPRAMINE	4	CACNA1F
HALOFANTRINE	4	CACNA1F
DROPERIDOL	4	CACNA1F
SAQUINAVIR	4	CACNA1F
DULOXETINE	4	CACNA1F
DIAZEPAM	4	CACNA1F
SERTINDOLE	4	CACNA1F
QUINIDINE	4	CACNA1F
LAMIVUDINE	4	CACNA1F
PIMOZIDE	4	CACNA1F

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
PLK4	303	Binding:293, Functional:10
CACNA1F	221	Binding:135, Functional:79, Toxicity:5, ADMET:2
ABHD12	35	Binding:31, Toxicity:3, ADMET:1
ELOVL1	22	Binding:22
KCNV2	21	Binding:20, Toxicity:1
CACNA2D4	13	Binding:13
PCDH15	9	Binding:9
CWC27	7	Binding:7
MED12	6	Binding:6
TTPA	5	Binding:5
NDUFA7	4	Binding:4
MFN2	3	Binding:3
USP45	3	Binding:3
OPA1	2	Binding:2
ADGRA3	2	Binding:2
TMEM126A	1	Binding:1
RHO	1	Binding:1
SSBP1	1	Binding:1
WFS1	1	Binding:1
NBAS	1	Binding:1
PANK2	1	Binding:1
PNPLA6	1	Binding:1
TUBGCP4	1	Binding:1
PMPCA	1	Binding:1
POMGNT1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
OPA1	3.6.5.5	dynamin GTPase
CWC27	5.2.1.8	peptidylprolyl isomerase
SPG7	3.4.24.B18
PLK4	2.7.11.21	polo kinase
ACO2	4.2.1.3	aconitate hydratase
PIGQ	2.4.1.198	phosphatidylinositol N-acetylglucosaminyltransferase
PANK2	2.7.1.33	pantothenate kinase
TRNT1	2.7.7.72	CCA tRNA nucleotidyltransferase
PMPCA	3.4.24.64	mitochondrial processing peptidase
POMGNT1	2.4.1.312	protein O-mannose beta-1,4-N-acetylglucosaminyltransferase
INPP5E	3.1.3.36	phosphoinositide 5-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PLK4	303
CACNA1F	221

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)
MOMELOTINIB	4	OPA1, PLK4
FEDRATINIB	4	PLK4
AXITINIB	4	PLK4
SORAFENIB	4	PLK4
RUXOLITINIB	4	PLK4
ENTRECTINIB	4	PLK4
DABRAFENIB	4	PLK4
FOSTAMATINIB	4	PLK4
CERITINIB	4	PLK4
VANDETANIB	4	PLK4
GILTERITINIB	4	PLK4
PAZOPANIB	4	PLK4
NINTEDANIB	4	PLK4
SUNITINIB	4	CACNA1F, PLK4
DASATINIB	4	CACNA1F, PLK4
ERLOTINIB	4	PLK4
CRIZOTINIB	4	PLK4
MIDOSTAURIN	4	PLK4
IMATINIB	4	PLK4
BEPRIDIL	4	CACNA1F
IMIPRAMINE	4	CACNA1F
HALOFANTRINE	4	CACNA1F
DROPERIDOL	4	CACNA1F
SAQUINAVIR	4	CACNA1F
DULOXETINE	4	CACNA1F
DIAZEPAM	4	CACNA1F
SERTINDOLE	4	CACNA1F
QUINIDINE	4	CACNA1F
LAMIVUDINE	4	CACNA1F
PIMOZIDE	4	CACNA1F

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	OPA1, PLK4, CACNA1F, ABHD12, CACNA2D4
B	Phased (≥1) drug, not yet approved	2	MED12, CWC27
C	Druggable family + PDB, no drug	8	RHO, SPG7, PANK2, TRNT1, POMGNT1, INPP5E, CNGA1, CNGA3
D	Druggable family + AlphaFold only, no drug	8	ACO2, USH2A, ADGRA3, PIGQ, ADGRV1, PMPCA, KCNV2, USP45
E	Difficult family or no structure, no drug	52	TMEM126A, NDUFA7, RGS9, RLBP1, ROM1, RP9, RPGR, SEMA4A, SEMA6B, SLC24A1 (+42 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CABP4	0	CACNA1F
TMEM126A	1	—
NDUFA7	4	—
RGS9	0	—
RHO	1	—
RLBP1	0	—
ROM1	0	—
RP9	0	—
RPGR	0	—
SEMA4A	0	—
SEMA6B	0	—
SLC24A1	0	—
SNAP25	0	—
SPG7	0	—
SSBP1	1	—
ACO2	0	—
TTPA	5	—
USH1C	0	—
USH2A	0	—
CLRN1	0	—
WFS1	1	—
SCAPER	0	—
ARL6	0	—
ESPN	0	—
RPGRIP1	0	—
ABITRAM	0	—
CDH23	0	—
ADGRA3	2	—
PIGQ	0	—
C1QTNF5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE1/PHASE2	2
PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEFERIPRONE	4	1
SITAGLIPTIN	4	1