Stargardt disease 3

Summary

Stargardt disease 3 (MONDO:0010819) is a disease caused by ELOVL4 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Causal gene: ELOVL4 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 99
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Stargardt disease 3
Mondo ID	MONDO:0010819
MeSH	C535805
OMIM	600110
DOID	DOID:0061238
UMLS	C1838644
MedGen	333146
GARD	0015314
Is cancer (heuristic)	no

Also known as: Stargardt disease 3 · Stargardt disease type 3 · STGD3

Data availability: 99 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › Stargardt disease › Stargardt disease 3

Related subtypes (3): severe early-childhood-onset retinal dystrophy, 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

99 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 19 pathogenic, 17 benign, 9 conflicting classifications of pathogenicity, 7 pathogenic/likely pathogenic, 3 benign/likely benign, 3 likely benign, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1386202	NM_000350.3(ABCA4):c.1766G>A (p.Trp589Ter)	ABCA4	Pathogenic	criteria provided, single submitter
2024100	NM_000350.3(ABCA4):c.1994del (p.Tyr665fs)	ABCA4	Pathogenic	criteria provided, single submitter
236096	NM_000350.3(ABCA4):c.2894A>G (p.Asn965Ser)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
288341	NM_000350.3(ABCA4):c.2023G>A (p.Val675Ile)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3237362	NM_000350.3(ABCA4):c.67-1dup	ABCA4	Pathogenic	no assertion criteria provided
3237363	NM_000350.3(ABCA4):c.265G>T (p.Glu89Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
522787	NM_000350.3(ABCA4):c.1819G>C (p.Gly607Arg)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
7898	NM_000350.3(ABCA4):c.634C>T (p.Arg212Cys)	ABCA4	Pathogenic	reviewed by expert panel
7899	NM_000350.3(ABCA4):c.52C>T (p.Arg18Trp)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
7905	NM_000350.3(ABCA4):c.2888del (p.Gly963fs)	ABCA4	Pathogenic	reviewed by expert panel
829880	NM_000350.3(ABCA4):c.488_491del (p.Leu163fs)	ABCA4	Pathogenic	criteria provided, single submitter
960785	NM_000350.3(ABCA4):c.1417_1420dup (p.Thr474fs)	ABCA4	Pathogenic	criteria provided, single submitter
966011	NM_000350.3(ABCA4):c.735T>G (p.Tyr245Ter)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
971758	NM_000350.3(ABCA4):c.2905A>G (p.Lys969Glu)	ABCA4	Pathogenic	criteria provided, single submitter
99035	NM_000350.3(ABCA4):c.1222C>T (p.Arg408Ter)	ABCA4	Pathogenic	reviewed by expert panel
99070	NM_000350.3(ABCA4):c.1648G>A (p.Gly550Arg)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99082	NM_000350.3(ABCA4):c.1798G>T (p.Asp600Tyr)	ABCA4	Pathogenic	criteria provided, single submitter
99083	NM_000350.3(ABCA4):c.179C>T (p.Ala60Val)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99084	NM_000350.3(ABCA4):c.1804C>T (p.Arg602Trp)	ABCA4	Pathogenic	reviewed by expert panel
99104	NM_000350.3(ABCA4):c.1937+1G>A	ABCA4	Pathogenic	reviewed by expert panel
99114	NM_000350.3(ABCA4):c.2041C>T (p.Arg681Ter)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143056	NM_022726.4(ELOVL4):c.504G>C (p.Leu168Phe)	ELOVL4	Pathogenic	criteria provided, multiple submitters, no conflicts
435057	NM_022726.4(ELOVL4):c.512T>C (p.Ile171Thr)	ELOVL4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4939	NM_022726.4(ELOVL4):c.790_794del (p.Asn264fs)	ELOVL4	Pathogenic	criteria provided, multiple submitters, no conflicts
4940	NM_022726.4(ELOVL4):c.789_793delinsAAC (p.Asn264fs)	ELOVL4	Pathogenic	no assertion criteria provided
4941	NM_022726.4(ELOVL4):c.810C>G (p.Tyr270Ter)	ELOVL4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3237364	NM_000350.3(ABCA4):c.438del (p.Ile146fs)	ABCA4	Likely pathogenic	no assertion criteria provided
929305	NM_000350.3(ABCA4):c.1248_1554+248del	ABCA4	Likely pathogenic	criteria provided, single submitter
7913	NM_000350.3(ABCA4):c.2828G>A (p.Arg943Gln)	ABCA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
866516	NM_000350.3(ABCA4):c.868C>T (p.Arg290Trp)	ABCA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 6 · 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

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

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	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…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

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

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mammalian vulva	1
upper arm skin	1
upper leg skin	1
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1
primordial germ cell in gonad	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

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ELOVL4	2,115
ABCA4	1,532

Intra-cohort edges

A	B	Sources
ABCA4	ELOVL4	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA4	P78363	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELOVL4	Q9GZR5	84.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 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 ABCA4 loss of function	1	5710.0×	0.002	ABCA4
Retinoid cycle disease events	1	1427.5×	0.002	ABCA4
Diseases associated with visual transduction	1	1427.5×	0.002	ABCA4
Diseases of the neuronal system	1	1427.5×	0.002	ABCA4
The canonical retinoid cycle in rods (twilight vision)	1	259.6×	0.008	ABCA4
Synthesis of very long-chain fatty acyl-CoAs	1	228.4×	0.008	ELOVL4
Visual phototransduction	1	129.8×	0.012	ABCA4
ABC-family protein mediated transport	1	60.7×	0.023	ABCA4
Sensory Perception	1	47.6×	0.026	ABCA4
Transport of small molecules	1	12.6×	0.086	ABCA4
Disease	1	6.5×	0.147	ABCA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
phospholipid transfer to membrane	1	2808.7×	0.004	ABCA4
fatty acid elongation, monounsaturated fatty acid	1	1203.7×	0.004	ELOVL4
fatty acid elongation, polyunsaturated fatty acid	1	1203.7×	0.004	ELOVL4
fatty acid elongation, saturated fatty acid	1	1053.2×	0.004	ELOVL4
phototransduction, visible light	1	648.1×	0.004	ABCA4
very long-chain fatty acid biosynthetic process	1	648.1×	0.004	ELOVL4
retinal metabolic process	1	468.1×	0.005	ABCA4
long-chain fatty-acyl-CoA biosynthetic process	1	421.3×	0.005	ELOVL4
unsaturated fatty acid biosynthetic process	1	324.1×	0.005	ELOVL4
phospholipid translocation	1	312.1×	0.005	ABCA4
retinoid metabolic process	1	247.8×	0.006	ABCA4
sphingolipid biosynthetic process	1	179.3×	0.007	ELOVL4
photoreceptor cell maintenance	1	179.3×	0.007	ABCA4
fatty acid biosynthetic process	1	175.5×	0.007	ELOVL4
lipid transport	1	131.7×	0.009	ABCA4
transmembrane transport	1	84.3×	0.013	ABCA4
visual perception	1	39.8×	0.025	ABCA4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ELOVL4	0	0
ABCA4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ELOVL4	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

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	0
C	Druggable family + PDB, no drug	1	ABCA4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ELOVL4

Undrugged target profiles

2 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	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04281732	Not specified	UNKNOWN	Visual Performance Measures in a Virtual Reality Environment for Assessing Clinical Trial Outcomes in Those With Severely Reduced Vision