Stargardt disease

disease

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Also known as fundus flavimaculatusjuvenile onset macular degenerationStargardt 1Stargardt disease 1Stargardt macular dystrophy

Summary

Stargardt disease (MONDO:0019353) is a disease with 21 cohort genes and 49 clinical trials. Top therapeutic interventions include metformin, disulfiram, and gildeuretinol.

At a glance

Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
Cohort genes: 21
ClinVar variants: 278
Phenotypes (HPO): 16
Clinical trials: 49

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	13	Europe	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0007663	Reduced visual acuity	Obligate (100%)
HP:0000493	Abnormal foveal morphology	Very frequent (80-99%)
HP:0000551	Color vision defect	Very frequent (80-99%)
HP:0000603	Central scotoma	Very frequent (80-99%)
HP:0000608	Macular degeneration	Very frequent (80-99%)
HP:0000610	Abnormal choroid morphology	Very frequent (80-99%)
HP:0000649	Abnormality of visual evoked potentials	Very frequent (80-99%)
HP:0000662	Nyctalopia	Very frequent (80-99%)
HP:0007704	Paroxysmal involuntary eye movements	Very frequent (80-99%)
HP:0007722	Retinal pigment epithelial atrophy	Very frequent (80-99%)
HP:0007814	Retinal pigment epithelial mottling	Very frequent (80-99%)
HP:0008002	Abnormality of macular pigmentation	Very frequent (80-99%)
HP:0030329	Retinal thinning	Very frequent (80-99%)
HP:0008059	Aplasia/Hypoplasia of the macula	Frequent (30-79%)
HP:0030500	Yellow/white lesions of the macula	Frequent (30-79%)
HP:0030786	Photopsia	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Stargardt disease
Mondo ID	MONDO:0019353
MeSH	D000080362
OMIM	248200
Orphanet	827
DOID	DOID:0050817
ICD-11	1690038580
NCIT	C85078
SNOMED CT	47673003
UMLS	C0271093
MedGen	75734
GARD	0000181
MedDRA	10062766
Is cancer (heuristic)	no

Also known as: fundus flavimaculatus · juvenile onset macular degeneration · Stargardt 1 · Stargardt disease 1 · Stargardt macular dystrophy

Data availability: 278 ClinVar variants · 3 GenCC gene-disease records · 46 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Subtypes (4): severe early-childhood-onset retinal dystrophy, Stargardt disease 3, Stargardt disease 4, Stargardt disease 5

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

278 retrieved; paginated sample, class counts are floors:

94 pathogenic, 86 pathogenic/likely pathogenic, 40 conflicting classifications of pathogenicity, 28 likely pathogenic, 23 uncertain significance, 5 likely benign, 1 pathogenic; drug response, 1 pathogenic/likely pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
236068	NM_000350.2(ABCA4):c.[1A>G;6089G>A]		Pathogenic	no assertion criteria provided
635154	NM_000350.2(ABCA4):c.[5512C>G;5882G>A]		Pathogenic	no assertion criteria provided
1000328	NM_000350.3(ABCA4):c.5691G>T (p.Gln1897His)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1001082	NM_000350.3(ABCA4):c.1019A>C (p.Tyr340Ser)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048145	NM_000350.3(ABCA4):c.6122G>A (p.Gly2041Asp)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067270	NM_000350.3(ABCA4):c.95C>T (p.Pro32Leu)	ABCA4	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
1350758	NM_000350.3(ABCA4):c.2522A>C (p.Gln841Pro)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1350865	NM_000350.3(ABCA4):c.53G>A (p.Arg18Gln)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
1351564	NM_000350.3(ABCA4):c.2908del (p.Thr970fs)	ABCA4	Pathogenic	criteria provided, single submitter
1383864	NM_000350.3(ABCA4):c.2741_2742del (p.His914fs)	ABCA4	Pathogenic	criteria provided, single submitter
1429394	NM_000350.3(ABCA4):c.2807del (p.Lys936fs)	ABCA4	Pathogenic	criteria provided, single submitter
1435338	NM_000350.3(ABCA4):c.6181_6184del (p.Thr2061fs)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
1452669	NM_000350.3(ABCA4):c.2972G>T (p.Gly991Val)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456034	NM_000350.3(ABCA4):c.3304G>T (p.Asp1102Tyr)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457682	NM_000350.3(ABCA4):c.4102C>T (p.Arg1368Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460063	NM_000350.3(ABCA4):c.4720G>T (p.Glu1574Ter)	ABCA4	Pathogenic	reviewed by expert panel
1803948	NM_000350.3(ABCA4):c.768+1G>A	ABCA4	Pathogenic	no assertion criteria provided
1803949	NM_000350.3:c.1876_1999del	ABCA4	Pathogenic	no assertion criteria provided
1803951	NM_000350.3(ABCA4):c.3898del (p.Arg1300fs)	ABCA4	Pathogenic	no assertion criteria provided
1804173	NM_000350.3(ABCA4):c.3608-1G>A	ABCA4	Pathogenic	no assertion criteria provided
1804636	NM_000350.3(ABCA4):c.2453G>C (p.Gly818Ala)	ABCA4	Pathogenic	no assertion criteria provided
1804641	NM_000350.3(ABCA4):c.4243dup (p.Thr1415fs)	ABCA4	Pathogenic	no assertion criteria provided
2033572	NM_000350.3(ABCA4):c.4254-5T>A	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2202780	NM_000350.3(ABCA4):c.6289C>T (p.Pro2097Ser)	ABCA4	Pathogenic	reviewed by expert panel
2202817	NM_000350.3(ABCA4):c.2T>C (p.Met1Thr)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236093	NM_000350.3(ABCA4):c.2609C>T (p.Pro870Leu)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236095	NM_000350.3(ABCA4):c.2875A>G (p.Thr959Ala)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236096	NM_000350.3(ABCA4):c.2894A>G (p.Asn965Ser)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236102	NM_000350.3(ABCA4):c.3482G>A (p.Arg1161His)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 35 · Orphanet: 73 · 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
ELOVL4	Definitive	Autosomal dominant	Stargardt disease 3	13
ABCA4	Supportive	Autosomal dominant	Stargardt disease	12
PROM1	Supportive	Autosomal dominant	Stargardt disease	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELOVL4	Orphanet:1955	Spinocerebellar ataxia type 34
ELOVL4	Orphanet:352333	Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome
ELOVL4	Orphanet:827	Stargardt disease
ABCA4	Orphanet:1872	Cone rod dystrophy
ABCA4	Orphanet:791	Retinitis pigmentosa
ABCA4	Orphanet:827	Stargardt disease
PROM1	Orphanet:1872	Cone rod dystrophy
PROM1	Orphanet:319640	Retinal macular dystrophy type 2
PROM1	Orphanet:791	Retinitis pigmentosa
PROM1	Orphanet:827	Stargardt disease
RP2	Orphanet:791	Retinitis pigmentosa
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
TULP1	Orphanet:65	Leber congenital amaurosis
TULP1	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
RP1L1	Orphanet:247834	Occult macular dystrophy
RP1L1	Orphanet:791	Retinitis pigmentosa
KCNV2	Orphanet:209932	Cone dystrophy with supernormal rod response
RDH12	Orphanet:65	Leber congenital amaurosis
RDH12	Orphanet:791	Retinitis pigmentosa
EYS	Orphanet:791	Retinitis pigmentosa
CERKL	Orphanet:791	Retinitis pigmentosa
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita

Cohort genes → proteins

21 cohort genes, 21 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	21

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELOVL4	HGNC:14415	ENSG00000118402	Q9GZR5	Very long chain fatty acid elongase 4	gencc,clinvar
ABCA4	HGNC:34	ENSG00000198691	P78363	Retinal-specific phospholipid-transporting ATPase ABCA4	gencc,clinvar
PROM1	HGNC:9454	ENSG00000007062	O43490	Prominin-1	gencc,clinvar
RP2	HGNC:10274	ENSG00000102218	O75695	Protein XRP2	clinvar
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	clinvar
TULP1	HGNC:12423	ENSG00000112041	O00294	Tubby-related protein 1	clinvar
BEST1	HGNC:12703	ENSG00000167995	O76090	Bestrophin-1	clinvar
RP1L1	HGNC:15946	ENSG00000183638	Q8IWN7	Retinitis pigmentosa 1-like 1 protein	clinvar
KCNV2	HGNC:19698	ENSG00000168263	Q8TDN2	Potassium voltage-gated channel subfamily V member 2	clinvar
RDH12	HGNC:19977	ENSG00000139988	Q96NR8	Retinol dehydrogenase 12	clinvar
EYS	HGNC:21555	ENSG00000188107	Q5T1H1	Protein eyes shut homolog	clinvar
CERKL	HGNC:21699	ENSG00000188452	Q49MI3	Ceramide kinase-like protein	clinvar
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	clinvar
CRB1	HGNC:2343	ENSG00000134376	P82279	Protein crumbs homolog 1	clinvar
CRX	HGNC:2383	ENSG00000105392	O43186	Cone-rod homeobox protein	clinvar
FLVCR1	HGNC:24682	ENSG00000162769	Q9Y5Y0	Choline/ethanolamine transporter FLVCR1	clinvar
LRIT3	HGNC:24783	ENSG00000183423	Q3SXY7	Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3	clinvar
SNRNP200	HGNC:30859	ENSG00000144028	O75643	U5 small nuclear ribonucleoprotein 200 kDa helicase	clinvar
PCARE	HGNC:34383	ENSG00000179270	A6NGG8	Photoreceptor cilium actin regulator	clinvar
OPA1	HGNC:8140	ENSG00000198836	O60313	Dynamin-like GTPase OPA1, mitochondrial	clinvar
PRPH2	HGNC:9942	ENSG00000112619	P23942	Peripherin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELOVL4	Very long chain fatty acid elongase 4	Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.
ABCA4	Retinal-specific phospholipid-transporting ATPase ABCA4	Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leafl…
PROM1	Prominin-1	May play a role in cell differentiation, proliferation and apoptosis.
RP2	Protein XRP2	Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane.
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.
TULP1	Tubby-related protein 1	Required for normal development of photoreceptor synapses.
BEST1	Bestrophin-1	Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+).
RP1L1	Retinitis pigmentosa 1-like 1 protein	Required for the differentiation of photoreceptor cells.
KCNV2	Potassium voltage-gated channel subfamily V member 2	Potassium channel subunit.
RDH12	Retinol dehydrogenase 12	Retinoids dehydrogenase/reductase with a clear preference for NADP.
EYS	Protein eyes shut homolog	Required to maintain the integrity of photoreceptor cells.
CERKL	Ceramide kinase-like protein	Has no detectable ceramide-kinase activity.
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.
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.
FLVCR1	Choline/ethanolamine transporter FLVCR1	Uniporter that mediates the transport of extracellular choline and ethanolamine into cells, thereby playing a key role in phospholipid biosynthesis.
LRIT3	Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3	Plays a role in the synapse formation and synaptic transmission between cone photoreceptor cells and retinal bipolar cells.
SNRNP200	U5 small nuclear ribonucleoprotein 200 kDa helicase	Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.
PCARE	Photoreceptor cilium actin regulator	Plays an essential role for normal photoreceptor cell maintenance and vision.
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.
PRPH2	Peripherin-2	Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure.

Protein-family classification

Druggable: 8 · Difficult: 1 · Unknown: 12 · Druggable fraction: 0.38

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
Transporter	2	7.4×	0.206
Ion channel	1	5.3×	0.591
Enzyme (other)	3	1.7×	0.591
Antibody/Immunoglobulin	1	1.4×	0.632
Kinase	1	1.3×	0.632
Other/Unknown	12	1.0×	0.632
Transcription factor	1	0.4×	0.934

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELOVL4	Other/Unknown	no		ELO_fam, ELO_CS, ELOVL4
ABCA4	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR
PROM1	Other/Unknown	no		Prominin
RP2	Other/Unknown	no		CARP_motif, Tubulin-bd_cofactor_C_dom, CAP/MinC_C
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
TULP1	Other/Unknown	no		Tubby_C, Tubby_C_CS, Tubby-like_C
BEST1	Other/Unknown	no		Bestrophin, Bestrophin-like
RP1L1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
KCNV2	Ion channel	yes		T1-type_BTB, K_chnl_volt-dep_Kv, K_chnl_volt-dep_Kv5/Kv9
RDH12	Enzyme (other)	yes	1.1.1.105	SDR_fam, NAD(P)-bd_dom_sf
EYS	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
CERKL	Kinase	yes		Diacylglycerol_kinase_cat_dom, NAD/diacylglycerol_kinase_sf, ATP-NAD_kinase_N
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
CRB1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
CRX	Transcription factor	no		HD, Homeodomain-like_sf, Otx_TF_C
FLVCR1	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
LRIT3	Antibody/Immunoglobulin	yes		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, Ig_sub2
SNRNP200	Enzyme (other)	yes	3.6.4.13	Helicase_C-like, Sec63-dom, DEAD/DEAH_box_helicase_dom
PCARE	Other/Unknown	no		PCARE
OPA1	Enzyme (other)	yes	3.6.5.5	Dynamin_GTPase, Dynamin, P-loop_NTPase
PRPH2	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS

Expression context

Cohort genes with no expression data: 0.

19 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)	21
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	6
male germ line stem cell (sensu Vertebrata) in testis	5
pigmented layer of retina	3
mammalian vulva	2
upper arm skin	2
retina	2
islet of Langerhans	2
endothelial cell	2
ventricular zone	2
hindlimb stylopod muscle	2
upper leg skin	1
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1
leukocyte	1
monocyte	1
mononuclear cell	1
left ovary	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELOVL4	228	ubiquitous	marker	upper leg skin, upper arm skin, mammalian vulva
ABCA4	164	tissue_specific	marker	pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
PROM1	252	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
RP2	242	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
TULP1	134	tissue_specific	marker	primordial germ cell in gonad, tendon of biceps brachii, retina
BEST1	209	ubiquitous	marker	pigmented layer of retina, lateral globus pallidus, inferior olivary complex
RP1L1	30	tissue_specific	yes	primordial germ cell in gonad, buccal mucosa cell, bone marrow cell
KCNV2	61	tissue_specific	marker	sperm, male germ cell, primordial germ cell in gonad
RDH12	180	tissue_specific	marker	upper arm skin, skin of leg, mammalian vulva
EYS	153	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, islet of Langerhans
CERKL	122	tissue_specific	marker	islet of Langerhans, olfactory segment of nasal mucosa, male germ line stem cell (sensu Vertebrata) in testis
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis
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
FLVCR1	240	ubiquitous	marker	jejunal mucosa, ileal mucosa, epithelial cell of pancreas
LRIT3	114	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, superior frontal gyrus, cerebellar hemisphere
SNRNP200	294	ubiquitous	marker	ventricular zone, endometrium epithelium, embryo
PCARE	78	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, apex of heart, hindlimb stylopod muscle
OPA1	288	ubiquitous	marker	adrenal tissue, calcaneal tendon, endothelial cell
PRPH2	176	tissue_specific	marker	quadriceps femoris, vastus lateralis, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 38.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SNRNP200	4,118
RDH12	3,526
MED12	3,322
PROM1	3,302
OPA1	2,630
COL2A1	2,491
ELOVL4	2,115
CRX	2,076
LRIT3	1,992
KCNV2	1,908

Intra-cohort edges

A	B	Sources
ABCA4	BEST1	string_interaction
ABCA4	CERKL	string_interaction
ABCA4	ELOVL4	string_interaction
ABCA4	EYS	string_interaction
ABCA4	KCNV2	string_interaction
ABCA4	PCARE	string_interaction
ABCA4	PROM1	string_interaction
ABCA4	PRPH2	string_interaction
ABCA4	RDH12	string_interaction
ABCA4	RP1L1	string_interaction
ABCA4	TULP1	string_interaction
BEST1	CRX	string_interaction
BEST1	ELOVL4	string_interaction
BEST1	EYS	string_interaction
BEST1	PRPH2	string_interaction
BEST1	RDH12	string_interaction
CERKL	EYS	string_interaction
CERKL	PCARE	string_interaction
CERKL	RDH12	string_interaction
CERKL	RP1L1	string_interaction
CERKL	TULP1	string_interaction
CRX	PRPH2	string_interaction
CRX	RDH12	string_interaction
CRX	TULP1	string_interaction
ELOVL4	PROM1	string_interaction
ELOVL4	PRPH2	string_interaction
EYS	PCARE	string_interaction
EYS	PRPH2	string_interaction
EYS	RDH12	string_interaction
EYS	RP1L1	string_interaction
EYS	TULP1	string_interaction
MED12	SNRNP200	biogrid_interaction
PCARE	RDH12	string_interaction
PCARE	RP1L1	string_interaction
PCARE	TULP1	string_interaction
PRPH2	RP1L1	string_interaction
PRPH2	TULP1	string_interaction
RDH12	TULP1	string_interaction

Structural data

PDB: 13 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SNRNP200	O75643	81
BEST1	O76090	19
COL2A1	P02458	11
OPA1	O60313	11
ABCA4	P78363	8
FLVCR1	Q9Y5Y0	8
RP2	O75695	3
MED12	Q93074	3
TULP1	O00294	2
CRB1	P82279	1
CRX	O43186	1
PCARE	A6NGG8	1
PRPH2	P23942	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RDH12	Q96NR8	92.21
PROM1	O43490	85.68
ELOVL4	Q9GZR5	84.53
CERKL	Q49MI3	79.82
KCNV2	Q8TDN2	75.55
LRIT3	Q3SXY7	70.06
RP1L1	Q8IWN7	38.97
EYS	Q5T1H1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 57. Enrichment computed across 21 evidence-associated genes (12 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 12 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)	2	86.5×	0.013	ABCA4, RDH12
Defective visual phototransduction due to RDH12 loss of function	1	951.7×	0.017	RDH12
Defective visual phototransduction due to ABCA4 loss of function	1	951.7×	0.017	ABCA4
Developmental Lineage of Pancreatic Ductal Cells	2	38.1×	0.017	PROM1, COL2A1
Retinoid cycle disease events	1	237.9×	0.034	ABCA4
Diseases associated with visual transduction	1	237.9×	0.034	ABCA4
Diseases of the neuronal system	1	237.9×	0.034	ABCA4
Trafficking of myristoylated proteins to the cilium	1	190.3×	0.037	RP2
Regulation of Apoptosis	1	158.6×	0.040	OPA1
Heme biosynthesis	1	63.4×	0.089	FLVCR1
Fibronectin matrix formation	1	47.6×	0.108	COL2A1
Synthesis of very long-chain fatty acyl-CoAs	1	38.1×	0.123	ELOVL4
MET activates PTK2 signaling	1	31.7×	0.136	COL2A1
Iron uptake and transport	1	28.8×	0.136	FLVCR1
Visual phototransduction	1	21.6×	0.136	ABCA4
Collagen chain trimerization	1	21.6×	0.136	COL2A1
Signaling by PDGF	1	21.1×	0.136	COL2A1
NCAM1 interactions	1	20.7×	0.136	COL2A1
Voltage gated Potassium channels	1	20.2×	0.136	KCNV2
mRNA Splicing - Minor Pathway	1	18.7×	0.136	SNRNP200
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	18.0×	0.136	MED12
Assembly of collagen fibrils and other multimeric structures	1	16.7×	0.136	COL2A1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	16.4×	0.136	MED12
Respiratory Syncytial Virus Infection Pathway	1	16.4×	0.136	MED12
Collagen degradation	1	14.6×	0.136	COL2A1
Collagen biosynthesis and modifying enzymes	1	14.2×	0.136	COL2A1
RSV-host interactions	1	13.0×	0.136	MED12
Adipogenesis	1	13.0×	0.136	MED12
Non-integrin membrane-ECM interactions	1	12.9×	0.136	COL2A1
Epigenetic regulation by WDR5-containing histone modifying complexes	1	12.9×	0.136	MED12

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 21 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	12	45.4×	5e-16	ABCA4, RP2, TULP1, BEST1, RP1L1, RDH12, COL2A1, CRX (+4 more)
photoreceptor cell maintenance	6	102.4×	1e-09	ABCA4, PROM1, TULP1, RP1L1, RDH12, CRB1
detection of light stimulus involved in visual perception	5	154.3×	6e-09	TULP1, BEST1, EYS, CRB1, PRPH2
photoreceptor cell outer segment organization	4	200.6×	1e-07	RP1L1, CRB1, PCARE, PRPH2
retina development in camera-type eye	4	48.6×	4e-05	TULP1, RP1L1, CRX, PRPH2
protein localization to photoreceptor outer segment	2	229.3×	8e-04	TULP1, PCARE
protein complex oligomerization	2	64.2×	0.009	BEST1, OPA1
retina layer formation	2	61.7×	0.009	PROM1, CRB1
retinoid metabolic process	2	47.2×	0.014	ABCA4, RDH12
spliceosome conformational change to release U4 (or U4atac) and U1 (or U11)	1	802.5×	0.015	SNRNP200
response to low light intensity stimulus	1	802.5×	0.015	PRPH2
camera-type eye photoreceptor cell development	1	802.5×	0.015	CRB1
mitochondrial inner membrane fusion	1	802.5×	0.015	OPA1
sphingolipid biosynthetic process	2	34.1×	0.018	ELOVL4, CERKL
cis assembly of pre-catalytic spliceosome	1	401.2×	0.021	SNRNP200
post-embryonic retina morphogenesis in camera-type eye	1	401.2×	0.021	CRB1
synapse assembly involved in innervation	1	401.2×	0.021	LRIT3
gamma-aminobutyric acid secretion, neurotransmission	1	401.2×	0.021	BEST1
glomerular parietal epithelial cell differentiation	1	401.2×	0.021	PROM1
phospholipid transfer to membrane	1	267.5×	0.024	ABCA4
establishment of bipolar cell polarity involved in cell morphogenesis	1	267.5×	0.024	CRB1
axis elongation involved in somitogenesis	1	267.5×	0.024	MED12
heme export	1	267.5×	0.024	FLVCR1
membrane tubulation	1	267.5×	0.024	OPA1
positive regulation of nephron tubule epithelial cell differentiation	1	267.5×	0.024	PROM1
heme transport	1	200.6×	0.029	FLVCR1
photoreceptor cell development	1	200.6×	0.029	RP1L1
neural tube closure	2	17.8×	0.032	MED12, OPA1
camera-type eye photoreceptor cell differentiation	1	160.5×	0.034	PROM1
otic vesicle development	1	133.8×	0.038	COL2A1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Emixustat	Phase 3 (in late-stage trials)
Tinlarebant	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 18

Druggability breadth: 6 of 21 evidence-associated genes (29%) 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
SNRNP200	GILTERITINIB
OPA1	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SNRNP200	2	4
OPA1	2	4
MED12	1	2
ELOVL4	0	0
ABCA4	0	0
PROM1	0	0
RP2	0	0
TULP1	0	0
BEST1	0	0
RP1L1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GILTERITINIB	4	SNRNP200
MOMELOTINIB	4	OPA1
TIVANTINIB	3	OPA1
MOLIBRESIB	2	MED12, SNRNP200

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
SNRNP200	25	Binding:25
KCNV2	21	Binding:20, Toxicity:1
MED12	6	Binding:6
COL2A1	2	Binding:2
OPA1	2	Binding:2
ELOVL4	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RDH12	1.1.1.105, 1.1.1.300	all-trans-retinol dehydrogenase (NAD+), NADP-retinol dehydrogenase
SNRNP200	3.6.4.13	RNA helicase
OPA1	3.6.5.5	dynamin GTPase

Pharmacogenomics

Cohort genes with a PharmGKB record: 21; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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)
GILTERITINIB	4	SNRNP200
MOMELOTINIB	4	OPA1
TIVANTINIB	3	OPA1
MOLIBRESIB	2	MED12, SNRNP200

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SNRNP200, OPA1
B	Phased (≥1) drug, not yet approved	1	MED12
C	Druggable family + PDB, no drug	2	ABCA4, FLVCR1
D	Druggable family + AlphaFold only, no drug	4	KCNV2, RDH12, CERKL, LRIT3
E	Difficult family or no structure, no drug	12	ELOVL4, PROM1, RP2, TULP1, BEST1, RP1L1, EYS, COL2A1, CRB1, CRX (+2 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ELOVL4	1	—
ABCA4	0	—
PROM1	0	—
RP2	0	—
TULP1	0	—
BEST1	0	—
RP1L1	0	—
KCNV2	21	—
RDH12	0	—
EYS	0	—
CERKL	0	—
COL2A1	2	—
CRB1	0	—
CRX	0	—
FLVCR1	0	—
LRIT3	0	—
PCARE	0	—
PRPH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 49.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	26
PHASE1/PHASE2	8
PHASE2	5
PHASE1	5
PHASE3	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05956626	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Phase 2/3 Trial to Assess the Efficacy and Safety of OCU410ST for Stargardt Disease
NCT06388083	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Phase 2/3 Study to Evaluate the Efficacy and Safety of Tinlarebant in Subjects With Stargardt Disease
NCT07419334	PHASE3	RECRUITING	Study of ALK-001 on the Progression of Stargardt Disease
NCT03772665	PHASE3	COMPLETED	Safety and Efficacy of Emixustat in Stargardt Disease
NCT05244304	PHASE3	COMPLETED	Phase 3, Randomized, Placebo-Controlled Study of Tinlarebant to Explore Safety and Efficacy in Adolescent Stargardt Disease
NCT02402660	PHASE2	ENROLLING_BY_INVITATION	Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease
NCT04239625	PHASE2	ACTIVE_NOT_RECRUITING	Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt Disease (TEASE)
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06300476	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of a Single Subretinal Injection of JWK006 Gene Therapy in Subjects With Stargardt Disease(STGD1)
NCT06467344	PHASE1/PHASE2	RECRUITING	Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR)
NCT06942572	PHASE1/PHASE2	RECRUITING	A Phase 1/2, First-in-Human Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of a Subretinal Injection of SB-007 in Subjects With Stargardt Disease (STGD1)
NCT07002398	PHASE1/PHASE2	RECRUITING	Safety and Preliminary Efficacy of VG801 in Patients With ABCA4 Mutation-associated Retinal Dystrophy (Stargardt Disease)
NCT07161544	PHASE1/PHASE2	RECRUITING	A Study of AAVB-039 in Participants With Stargardt Disease (STGD1)
NCT07439887	PHASE1/PHASE2	RECRUITING	Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety of a Single Intravitreal Injection of RTx-021 in Patients With Stargardt Disease
NCT03033108	PHASE2	COMPLETED	Pharmacodynamic Study of Emixustat Hydrochloride in Subjects With Macular Atrophy Secondary to Stargardt Disease
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
NCT05266014	PHASE1/PHASE2	COMPLETED	This is a Dose-finding Study Followed by 2-year Extension Study to Evaluate Safety and Tolerability of Tinlarebant in Adolescent Subjects With Stargardt Disease
NCT05417126	PHASE2	COMPLETED	Safety and Effects of a Single Intravitreal Injection of vMCO-010 Optogenetic Therapy in Subjects With Stargardt Disease
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT07417566	PHASE1	RECRUITING	A Study of DC6001 Tablet in Healthy Chinese Adult Subjects
NCT07594236	PHASE1	RECRUITING	Phase 1 Study of C.001 in Retinal Degeneration
NCT02230228	PHASE1	COMPLETED	Phase 1 Safety Study of ALK-001 in Healthy Volunteers
NCT03772938	PHASE1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT05674058	Not specified	ACTIVE_NOT_RECRUITING	Function and Imaging Assessments for G1961E-associated Stargardt Disease
NCT06048185	Not specified	ACTIVE_NOT_RECRUITING	Non-interventional Long Term Follow-up Study of Participants Previously Enrolled in the STARLIGHT Study
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06435000	Not specified	RECRUITING	An Observational Study in Subjects to Follow the Progression of Stargardt Disease Type 1 (STGD1) Caused by Bi-Allelic Autosomal Recessive Mutations in the ABCA4 Gene
NCT06445322	Not specified	RECRUITING	Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH)
NCT06591806	Not specified	RECRUITING	An Observational Study in Children and Adults With Stargardt Disease
NCT06805474	Not specified	RECRUITING	A Prospective Observational Study to Assess the Reliability and Validity of the MLSDT
NCT06989658	Not specified	NOT_YET_RECRUITING	Feasibility and Tolerability Study of Smart Contact Lens With Healthy Subjects and Patients With Stargardt’s Disease
NCT07265895	Not specified	NOT_YET_RECRUITING	Inherited Retinal Diseases: Natural History and Genotype-Phenotype Correlations
NCT07266584	Not specified	RECRUITING	Restoration of Central Vision With PRIMA in Patients With Photoreceptor Degeneration
NCT07298174	Not specified	NOT_YET_RECRUITING	Wide Field OCTA in Ocular Diseases
NCT07425574	Not specified	RECRUITING	A Study to Learn How Stargardt-type Eye Conditions Progress in Children and Adults
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT01676766	Not specified	TERMINATED	Novel Quantification Methods for Fluorescence to Detect Progression in Stargardt Disease
NCT01977846	Not specified	COMPLETED	A Natural History of the Progression of Stargardt Disease: Retrospective and Prospective Studies

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
METFORMIN	4	2
DISULFIRAM	4	1
GILDEURETINOL	3	3
TINLAREBANT	3	3
EMIXUSTAT	3	2
STG-001	2	1
CHEMBL4781327	0	2
CHEMBL4795596	0	2
CHEMBL5417591	0	1

Cohort genes: ELOVL4, ABCA4, PROM1, RP2, MED12, TULP1, BEST1, RP1L1, KCNV2, RDH12, EYS, CERKL, COL2A1, CRB1, CRX, FLVCR1, LRIT3, SNRNP200, PCARE, OPA1, PRPH2
Drugs: Metformin, Disulfiram, Gildeuretinol, Tinlarebant, Emixustat