Leber congenital amaurosis 1

Summary

Leber congenital amaurosis 1 (MONDO:0008764) is a disease caused by GUCY2D (GenCC Definitive), with 13 cohort genes and 3 clinical trials. Top therapeutic interventions include polymyxin b, trimethoprim, and zuretinol acetate.

At a glance

• Causal gene: GUCY2D (GenCC Definitive)
• Cohort genes: 13
• ClinVar variants: 1,515
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Leber congenital amaurosis 1
Mondo ID	MONDO:0008764
OMIM	204000
DOID	DOID:0110078
UMLS	C2931258
MedGen	419026
GARD	0000635
Is cancer (heuristic)	no

Also known as: amaurosis congenita of Leber, type 1 · CRB · GUCY2D Leber congenital amaurosis · LCA · LCA1 · Leber congenital amaurosis 1 · Leber congenital amaurosis caused by mutation in GUCY2D · Leber congenital amaurosis type 1

Data availability: 1,515 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Leber congenital amaurosis › Leber congenital amaurosis 1

Related subtypes (20): retinal aplasia, Leber congenital amaurosis 2, Leber congenital amaurosis 3, Leber congenital amaurosis 4, Leber congenital amaurosis 5, Leber congenital amaurosis 9, Leber congenital amaurosis 12, Leber congenital amaurosis 10, Leber congenital amaurosis 13, Leber congenital amaurosis 14, Leber congenital amaurosis 6, Leber congenital amaurosis 7, Leber congenital amaurosis 8, Leber congenital amaurosis 11, Leber congenital amaurosis 15, Leber congenital amaurosis 16, Leber congenital amaurosis 17, Leber congenital amaurosis 19, Leber congenital amaurosis with early-onset deafness, Leber congenital amaurosis 18

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

289 uncertain significance, 241 likely benign, 24 pathogenic, 15 benign, 13 likely pathogenic, 11 conflicting classifications of pathogenicity, 5 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066142	NM_000180.4(GUCY2D):c.-2_3del (p.Met1fs)	GUCY2D	Pathogenic	criteria provided, single submitter
1069546	NM_000180.4(GUCY2D):c.1361_1367del (p.Asn454fs)	GUCY2D	Pathogenic	criteria provided, single submitter
1070768	NM_000180.4(GUCY2D):c.2383C>T (p.Arg795Trp)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1070769	NM_000180.4(GUCY2D):c.2476C>T (p.Gln826Ter)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1072504	NM_000180.4(GUCY2D):c.484dup (p.Ala162fs)	GUCY2D	Pathogenic	criteria provided, single submitter
1074833	NM_000180.4(GUCY2D):c.2646C>G (p.Tyr882Ter)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1075556	NM_000180.4(GUCY2D):c.3105C>G (p.Tyr1035Ter)	GUCY2D	Pathogenic	criteria provided, single submitter
1076325	NM_000180.4(GUCY2D):c.564del (p.Ala189fs)	GUCY2D	Pathogenic	criteria provided, single submitter
1184899	NM_000180.4(GUCY2D):c.826del (p.Leu276fs)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1213843	NM_000180.4(GUCY2D):c.1567-1G>C	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1213844	NM_000180.4(GUCY2D):c.690_693del (p.Lys232fs)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1366687	NM_000180.4(GUCY2D):c.2260G>T (p.Glu754Ter)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1413732	NM_000180.4(GUCY2D):c.2871del (p.Ser958fs)	GUCY2D	Pathogenic	criteria provided, single submitter
1454622	NM_000180.4(GUCY2D):c.175del (p.Leu59fs)	GUCY2D	Pathogenic	criteria provided, single submitter
1456503	NM_000180.4(GUCY2D):c.2209C>T (p.Gln737Ter)	GUCY2D	Pathogenic	criteria provided, single submitter
1459421	NM_000180.4(GUCY2D):c.760G>T (p.Glu254Ter)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685872	NM_000180.4(GUCY2D):c.1A>G (p.Met1Val)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1685873	NM_000180.4(GUCY2D):c.2512C>G (p.Arg838Gly)	GUCY2D	Pathogenic	criteria provided, single submitter
1687499	NM_000180.4(GUCY2D):c.315C>A (p.Cys105Ter)	GUCY2D	Pathogenic	criteria provided, single submitter
1915862	NM_000180.4(GUCY2D):c.2678_2679del (p.Ser893fs)	GUCY2D	Pathogenic	criteria provided, single submitter
198995	NM_000180.4(GUCY2D):c.1773del (p.Asn591fs)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
2021991	NM_000180.4(GUCY2D):c.860del (p.Pro287fs)	GUCY2D	Pathogenic	criteria provided, single submitter
2046697	NM_000180.4(GUCY2D):c.2323C>T (p.Gln775Ter)	GUCY2D	Pathogenic	criteria provided, single submitter
2060321	NM_000180.4(GUCY2D):c.781_782insT (p.Glu261fs)	GUCY2D	Pathogenic	criteria provided, single submitter
2069382	NM_000180.4(GUCY2D):c.3118_3125delinsAAGGTGAGGTAC (p.Arg1040fs)	GUCY2D	Pathogenic	criteria provided, single submitter
2086516	NM_000180.4(GUCY2D):c.1150del (p.Asp384fs)	GUCY2D	Pathogenic	criteria provided, single submitter
2108666	NM_000180.4(GUCY2D):c.1821_1824dup (p.Ala609fs)	GUCY2D	Pathogenic	criteria provided, single submitter
2137915	NM_000180.4(GUCY2D):c.1762C>T (p.Arg588Trp)	GUCY2D	Pathogenic	reviewed by expert panel
2142901	NM_000180.4(GUCY2D):c.2291del (p.Pro764fs)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048129	NM_000180.4(GUCY2D):c.929C>A (p.Thr310Asn)	GUCY2D	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 31 · 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
GUCY2D	Definitive	Autosomal recessive	Leber congenital amaurosis 1	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GUCY2D	Orphanet:1872	Cone rod dystrophy
GUCY2D	Orphanet:65	Leber congenital amaurosis
GUCY2D	Orphanet:75377	Central areolar choroidal dystrophy
RP1	Orphanet:791	Retinitis pigmentosa
TULP1	Orphanet:65	Leber congenital amaurosis
TULP1	Orphanet:791	Retinitis pigmentosa
RPGRIP1	Orphanet:1872	Cone rod dystrophy
RPGRIP1	Orphanet:564	Meckel syndrome
RPGRIP1	Orphanet:65	Leber congenital amaurosis
CRB1	Orphanet:251295	Pigmented paravenous retinochoroidal atrophy
CRB1	Orphanet:35612	Nanophthalmos
CRB1	Orphanet:65	Leber congenital amaurosis
CRB1	Orphanet:791	Retinitis pigmentosa
CRX	Orphanet:1872	Cone rod dystrophy
CRX	Orphanet:65	Leber congenital amaurosis
CRX	Orphanet:791	Retinitis pigmentosa
LCA5	Orphanet:364055	Severe early-childhood-onset retinal dystrophy
LCA5	Orphanet:65	Leber congenital amaurosis
AIPL1	Orphanet:1872	Cone rod dystrophy
AIPL1	Orphanet:65	Leber congenital amaurosis
ALOX12B	Orphanet:281122	Self-improving collodion baby
ALOX12B	Orphanet:313	Lamellar ichthyosis
ALOX12B	Orphanet:79394	Congenital ichthyosiform erythroderma
LRAT	Orphanet:364055	Severe early-childhood-onset retinal dystrophy
LRAT	Orphanet:65	Leber congenital amaurosis
LRAT	Orphanet:791	Retinitis pigmentosa
MAPRE2	Orphanet:2505	Multiple benign circumferential skin creases on limbs
PROM1	Orphanet:1872	Cone rod dystrophy
PROM1	Orphanet:319640	Retinal macular dystrophy type 2
PROM1	Orphanet:791	Retinitis pigmentosa
PROM1	Orphanet:827	Stargardt disease

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GUCY2D	HGNC:4689	ENSG00000132518	Q02846	Retinal guanylyl cyclase 1	gencc,clinvar
RP1	HGNC:10263	ENSG00000104237	P56715	Oxygen-regulated protein 1	clinvar
TULP1	HGNC:12423	ENSG00000112041	O00294	Tubby-related protein 1	clinvar
RPGRIP1	HGNC:13436	ENSG00000092200	Q96KN7	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	clinvar
CRB1	HGNC:2343	ENSG00000134376	P82279	Protein crumbs homolog 1	clinvar
CRX	HGNC:2383	ENSG00000105392	O43186	Cone-rod homeobox protein	clinvar
CNTROB	HGNC:29616	ENSG00000170037	Q8N137	Centrobin	clinvar
LCA5	HGNC:31923	ENSG00000135338	Q86VQ0	Lebercilin	clinvar
AIPL1	HGNC:359	ENSG00000129221	Q9NZN9	Aryl-hydrocarbon-interacting protein-like 1	clinvar
ALOX12B	HGNC:430	ENSG00000179477	O75342	Arachidonate 12-lipoxygenase, 12R-type	clinvar
LRAT	HGNC:6685	ENSG00000121207	O95237	Lecithin retinol acyltransferase	clinvar
MAPRE2	HGNC:6891	ENSG00000166974	Q15555	Microtubule-associated protein RP/EB family member 2	clinvar
PROM1	HGNC:9454	ENSG00000007062	O43490	Prominin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GUCY2D	Retinal guanylyl cyclase 1	Catalyzes the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors.
RP1	Oxygen-regulated protein 1	Microtubule-associated protein regulating the stability and length of the microtubule-based axoneme of photoreceptors.
TULP1	Tubby-related protein 1	Required for normal development of photoreceptor synapses.
RPGRIP1	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	May function as scaffolding protein.
CRB1	Protein crumbs homolog 1	Plays a role in photoreceptor morphogenesis in the retina.
CRX	Cone-rod homeobox protein	Transcription factor that binds and transactivates the sequence 5’-TAATC[CA]-3’ which is found upstream of several photoreceptor-specific genes, including the opsin genes.
CNTROB	Centrobin	Required for centriole duplication.
LCA5	Lebercilin	Involved in intraflagellar protein (IFT) transport in photoreceptor cilia.
AIPL1	Aryl-hydrocarbon-interacting protein-like 1	May be important in protein trafficking and/or protein folding and stabilization.
ALOX12B	Arachidonate 12-lipoxygenase, 12R-type	Catalyzes the regio and stereo-specific incorporation of a single molecule of dioxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species.
LRAT	Lecithin retinol acyltransferase	Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters.
MAPRE2	Microtubule-associated protein RP/EB family member 2	Adapter protein that is involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes.
PROM1	Prominin-1	May play a role in cell differentiation, proliferation and apoptosis.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 9 · Druggable fraction: 0.23

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
Kinase	1	2.1×	0.506
Enzyme (other)	2	1.8×	0.506
Other/Unknown	9	1.2×	0.506
Transcription factor	1	0.6×	0.813

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GUCY2D	Kinase	yes	4.6.1.2	Prot_kinase_dom, A/G_cyclase, Ser-Thr/Tyr_kinase_cat_dom
RP1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
TULP1	Other/Unknown	no		Tubby_C, Tubby_C_CS, Tubby-like_C
RPGRIP1	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
CRB1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
CRX	Transcription factor	no		HD, Homeodomain-like_sf, Otx_TF_C
CNTROB	Other/Unknown	no		Centrobin
LCA5	Other/Unknown	no		Lebercilin-like, Lebercilin_dom
AIPL1	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, AIP/AIPL1/TTC9
ALOX12B	Enzyme (other)	yes	1.13.11.31	LipOase, PLAT/LH2_dom, LipOase_mml
LRAT	Enzyme (other)	yes	2.3.1.135	LRAT_dom, LRAT
MAPRE2	Other/Unknown	no		CH_dom, EB1_C, MAPRE
PROM1	Other/Unknown	no		Prominin

Expression context

Cohort genes with no expression data: 0.

12 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	3
buccal mucosa cell	2
male germ line stem cell (sensu Vertebrata) in testis	2
retina	2
tendon of biceps brachii	2
left testis	2
right testis	2
ventricular zone	2
pigmented layer of retina	2
bronchial epithelial cell	2
bronchus	2
esophagus mucosa	1
lower esophagus mucosa	1
olfactory segment of nasal mucosa	1
right uterine tube	1
sperm	1
endothelial cell	1
ganglionic eminence	1
mucosa of paranasal sinus	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GUCY2D	121	tissue_specific	marker	buccal mucosa cell, esophagus mucosa, lower esophagus mucosa
RP1	103	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, male germ line stem cell (sensu Vertebrata) in testis
TULP1	134	tissue_specific	marker	primordial germ cell in gonad, tendon of biceps brachii, retina
RPGRIP1	168	tissue_specific	marker	left testis, sperm, right testis
CRB1	163	broad	marker	ganglionic eminence, ventricular zone, endothelial cell
CRX	54	tissue_specific	marker	pigmented layer of retina, retina, primordial germ cell in gonad
CNTROB	239	ubiquitous	marker	left testis, right testis, ventricular zone
LCA5	214	ubiquitous	marker	mucosa of paranasal sinus, bronchial epithelial cell, bronchus
AIPL1	62	tissue_specific	marker	buccal mucosa cell, pancreatic ductal cell, tendon of biceps brachii
ALOX12B	168	broad	yes	skin of leg, skin of abdomen, zone of skin
LRAT	149	broad	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
MAPRE2	300	ubiquitous	marker	cortical plate, dorsal root ganglion, corpus callosum
PROM1	252	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 20.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PROM1	3,302
MAPRE2	2,195
CRX	2,076
CNTROB	1,884
RPGRIP1	1,422
ALOX12B	1,126
GUCY2D	1,083
CRB1	1,075
LCA5	1,027
LRAT	900

Intra-cohort edges

A	B	Sources
AIPL1	CRX	string_interaction
AIPL1	GUCY2D	string_interaction
AIPL1	LCA5	string_interaction
AIPL1	LRAT	string_interaction
AIPL1	RPGRIP1	string_interaction
AIPL1	TULP1	string_interaction
CRX	GUCY2D	string_interaction
CRX	LCA5	string_interaction
CRX	RP1	string_interaction
CRX	RPGRIP1	string_interaction
CRX	TULP1	string_interaction
GUCY2D	LCA5	string_interaction
GUCY2D	LRAT	string_interaction
GUCY2D	RPGRIP1	string_interaction
GUCY2D	TULP1	string_interaction
LCA5	LRAT	string_interaction
LCA5	RPGRIP1	string_interaction
LRAT	RPGRIP1	string_interaction
LRAT	TULP1	string_interaction
RPGRIP1	TULP1	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AIPL1	Q9NZN9	6
TULP1	O00294	2
RPGRIP1	Q96KN7	1
CRB1	P82279	1
CRX	O43186	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALOX12B	O75342	92.07
PROM1	O43490	85.68
LRAT	O95237	83.69
GUCY2D	Q02846	82.37
MAPRE2	Q15555	75.12
CNTROB	Q8N137	67.31
LCA5	Q86VQ0	64.05
RP1	P56715	37.45

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 13 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective visual phototransduction due to LRAT loss of function	1	1427.5×	0.006	LRAT
Retinoid cycle disease events	1	713.8×	0.006	LRAT
Diseases associated with visual transduction	1	713.8×	0.006	LRAT
Diseases of the neuronal system	1	713.8×	0.006	LRAT
Synthesis of 12-eicosatetraenoic acid derivatives	1	407.9×	0.009	ALOX12B
Arachidonate metabolism	1	142.8×	0.020	ALOX12B
The canonical retinoid cycle in rods (twilight vision)	1	129.8×	0.020	LRAT
Metabolism of fat-soluble vitamins	1	95.2×	0.024	LRAT
Inactivation, recovery and regulation of the phototransduction cascade	1	79.3×	0.025	GUCY2D
Visual phototransduction	1	64.9×	0.026	LRAT
Retinoid metabolism and transport	1	62.1×	0.026	LRAT
Developmental Lineage of Pancreatic Ductal Cells	1	57.1×	0.026	PROM1
Fatty acid metabolism	1	32.8×	0.042	ALOX12B
Metabolism of vitamins and cofactors	1	29.1×	0.044	LRAT
Sensory Perception	1	23.8×	0.047	LRAT
Metabolism	2	5.8×	0.047	ALOX12B, LRAT
Metabolism of lipids	1	7.9×	0.128	ALOX12B
Disease	1	3.3×	0.273	LRAT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 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	7	42.8×	6e-09	GUCY2D, RP1, TULP1, RPGRIP1, CRX, AIPL1, LRAT
photoreceptor cell maintenance	5	137.9×	7e-09	RP1, TULP1, CRB1, LCA5, PROM1
regulation of opsin-mediated signaling pathway	2	259.3×	4e-04	GUCY2D, AIPL1
retinal rod cell development	2	259.3×	4e-04	RP1, RPGRIP1
retina development in camera-type eye	3	58.9×	4e-04	RP1, TULP1, CRX
phototransduction, visible light	2	199.4×	6e-04	RP1, AIPL1
retina homeostasis	2	172.8×	6e-04	TULP1, AIPL1
photoreceptor cell outer segment organization	2	162.0×	6e-04	RP1, CRB1
cellular response to light stimulus	2	162.0×	6e-04	RP1, CRB1
retina layer formation	2	99.7×	0.001	CRB1, PROM1
detection of light stimulus involved in visual perception	2	99.7×	0.001	TULP1, CRB1
camera-type eye photoreceptor cell development	1	1296.3×	0.006	CRB1
positive regulation of lipid transport	1	648.1×	0.008	LRAT
post-embryonic retina morphogenesis in camera-type eye	1	648.1×	0.008	CRB1
glomerular parietal epithelial cell differentiation	1	648.1×	0.008	PROM1
mitotic cytokinetic process	1	648.1×	0.008	CNTROB
protein farnesylation	1	432.1×	0.010	AIPL1
positive regulation of ARF protein signal transduction	1	432.1×	0.010	MAPRE2
centrosome separation	1	432.1×	0.010	CNTROB
establishment of bipolar cell polarity involved in cell morphogenesis	1	432.1×	0.010	CRB1
positive regulation of nephron tubule epithelial cell differentiation	1	432.1×	0.010	PROM1
photoreceptor cell development	1	324.1×	0.012	RP1
protein lipidation	1	259.3×	0.013	ALOX12B
camera-type eye photoreceptor cell differentiation	1	259.3×	0.013	PROM1
positive regulation of mucus secretion	1	259.3×	0.013	ALOX12B
vitamin A metabolic process	1	185.2×	0.017	LRAT
protein localization to photoreceptor outer segment	1	185.2×	0.017	TULP1
phagocytosis, recognition	1	162.0×	0.018	TULP1
lipid oxidation	1	162.0×	0.018	ALOX12B
hepoxilin biosynthetic process	1	162.0×	0.018	ALOX12B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 12

Druggability breadth: 4 of 13 evidence-associated genes (31%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LRAT	1	3
GUCY2D	0	0
RP1	0	0
TULP1	0	0
RPGRIP1	0	0
CRB1	0	0
CRX	0	0
CNTROB	0	0
LCA5	0	0
AIPL1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FRAMYCETIN	3	LRAT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
RP1	1	Binding:1
AIPL1	1	Binding:1
LRAT	1	Binding:1
MAPRE2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GUCY2D	4.6.1.2	guanylate cyclase
ALOX12B	1.13.11.31	arachidonate 12-lipoxygenase
LRAT	2.3.1.135	phosphatidylcholine-retinol O-acyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
FRAMYCETIN	3	LRAT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	LRAT
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	GUCY2D, ALOX12B
E	Difficult family or no structure, no drug	10	RP1, TULP1, RPGRIP1, CRB1, CRX, CNTROB, LCA5, AIPL1, MAPRE2, PROM1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TULP1	0	LRAT
GUCY2D	0	—
RP1	1	—
RPGRIP1	0	—
CRB1	0	—
CRX	0	—
CNTROB	0	—
LCA5	0	—
AIPL1	1	—
ALOX12B	0	—
MAPRE2	1	—
PROM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03920007	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D
NCT01014052	PHASE1	COMPLETED	Safety/Proof of Concept Study of Oral QLT091001 in Subjects With Leber Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP) Due to Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT) Mutations
NCT01521793	PHASE1	COMPLETED	Repeated Treatments of QLT091001 in Subjects With Leber Congenital Amaurosis or Retinitis Pigmentosa (Extension of Study RET IRD 01)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
POLYMYXIN B	4	1
TRIMETHOPRIM	4	1
ZURETINOL ACETATE	2	2
CHEMBL15720	0	1
CHEMBL2397513	0	1
CHEMBL373756	0	1
CHEMBL3989738	0	1
CHEMBL4636958	0	1
CHEMBL5281080	0	1