ELOVL4

Summary

ELOVL4 (ELOVL fatty acid elongase 4, HGNC:14415) is a protein-coding gene on chromosome 6q14.1, encoding Very long chain fatty acid elongase 4 (Q9GZR5). Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.

This gene encodes a membrane-bound protein which is a member of the ELO family, proteins which participate in the biosynthesis of fatty acids. Consistent with the expression of the encoded protein in photoreceptor cells of the retina, mutations and small deletions in this gene are associated with Stargardt-like macular dystrophy (STGD3) and autosomal dominant Stargardt-like macular dystrophy (ADMD), also referred to as autosomal dominant atrophic macular degeneration.

Source: NCBI Gene 6785 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ELOVL4-related maculopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 359 total — 18 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 81
• Druggable target: yes
• MANE Select transcript: NM_022726

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14415
Approved symbol	ELOVL4
Name	ELOVL fatty acid elongase 4
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	CT118
Ensembl gene	ENSG00000118402
Ensembl biotype	protein_coding
OMIM	605512
Entrez	6785

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000369816

RefSeq mRNA: 1 — MANE Select: NM_022726 NM_022726

CCDS: CCDS4992

Canonical transcript exons

ENST00000369816 — 6 exons

Exon	Start	End
ENSE00000918611	79919420	79919547
ENSE00000918612	79921625	79921796
ENSE00000918613	79924952	79925032
ENSE00000918614	79926194	79926381
ENSE00001450988	79914814	79916883
ENSE00001450997	79947180	79947553

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4813 / max 445.6772, expressed in 1243 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74517	8.0246	1185
74519	0.5733	344
74520	0.3472	204
74518	0.2738	138
204080	0.1628	72
204079	0.0996	21

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	97.71	gold quality
upper arm skin	UBERON:0004263	96.35	gold quality
mammalian vulva	UBERON:0000997	96.24	gold quality
thymus	UBERON:0002370	93.69	gold quality
cerebellar vermis	UBERON:0004720	92.58	gold quality
penis	UBERON:0000989	91.64	gold quality
cortical plate	UBERON:0005343	91.58	gold quality
zone of skin	UBERON:0000014	91.53	gold quality
skin of abdomen	UBERON:0001416	91.16	gold quality
skin of leg	UBERON:0001511	91.09	gold quality
secondary oocyte	CL:0000655	90.12	gold quality
postcentral gyrus	UBERON:0002581	90.10	gold quality
orbitofrontal cortex	UBERON:0004167	89.92	gold quality
endothelial cell	CL:0000115	89.78	gold quality
gingival epithelium	UBERON:0001949	89.77	gold quality
gingiva	UBERON:0001828	89.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.35	gold quality
superior frontal gyrus	UBERON:0002661	89.30	gold quality
CA1 field of hippocampus	UBERON:0003881	89.00	gold quality
pons	UBERON:0000988	88.73	gold quality
oocyte	CL:0000023	88.71	gold quality
parietal lobe	UBERON:0001872	88.50	gold quality
primary visual cortex	UBERON:0002436	88.49	gold quality
choroid plexus epithelium	UBERON:0003911	88.42	gold quality
entorhinal cortex	UBERON:0002728	88.15	gold quality
middle temporal gyrus	UBERON:0002771	87.41	gold quality
tongue squamous epithelium	UBERON:0006919	87.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.81	gold quality
prefrontal cortex	UBERON:0000451	86.70	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	2233.87
E-MTAB-8142	yes	1097.68
E-MTAB-7316	yes	46.29
E-MTAB-5061	yes	5.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting ELOVL4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 39)

• mutational analysis shows ELOVL4 is not involved in the pathogenesis of RP25 (PMID:11474659)
• Recessive retinitis pigmentosa and Leber congenital amaurosis are rarely if ever associated with changes in the ELOVL4 gene. (PMID:12592226)
• The ELOVL4 gene is highly conserved throughout evolution and is expressed in the photoreceptor cells of the retina in a variety of different species (PMID:12824221)
• DNA sequence analysis showed a 5-bp deletion in exon 6 of the ELOVL4 gene, confirming the diagnosis of autosomal dominant Stargardt-like macular dystrophy. (PMID:12967813)
• mutations in ELOVL4 result in the intracellular misrouting of the protein in macular degeneration (PMID:15028284)
• ELOVL4 contributes to the autosomal dominant inheritance of Stargardt-like macular dystrophy (PMID:16036915)
• analysis of non-pathogenic polymorphisms in the ELOVL4 in Chinese patients with autosomal dominant STGD3-like macular dystrophy (PMID:16364203)
• This study demonstrates that dietary factors can influence the severity of an inherited human macular dystrophy. (PMID:16476896)
• No association with AMD was detected with Met299Val polymorphism in the ELOVL4 gene in the familial or sporadic cases compared to non-AMD or blood donor controls. (PMID:16885922)
• Role for Elovl4 in acylceramide synthesis, and in particular, a role in the synthesis of the unique very long chain C30-C40 fatty acids present in skin acylceramides. (PMID:17356513)
• Pathogenic mutations found in the ELOVL4 gene result in altered trafficking of the protein and behave with a dominant negative effect. (PMID:20096366)
• There was no association between the M299V variant in ELOVL4 gene and exudative age-related macular degeneration in a Chinese population. (PMID:20388345)
• Not only the ELOVL4-ELOVL4DeltaC homo-oligomeric interaction, but also several hetero-oligomeric interactions, may contribute to the pathology of Stargardt disease 3. (PMID:21139992)
• recessive mutations in ELOVL4 as the cause of a neuro-ichthyotic disease (PMID:22100072)
• Mutation in ELOVL4 gene is associated with Stargardt Disease. (PMID:22863181)
• 5 single nucleotide polymorphisms (SNPs: rs3812153, rs7764439, rs390659, rs434102 and c:929G>A) were detected in ELOVL4. (PMID:22948568)
• Coexpression of different forms of wild-type and mutant ELOVL4 revealed a large dominant-negative effect of mutant protein on ELOVL4 localization and enzymatic activity, resulting in reduced VLC-PUFA synthesis. (PMID:23509295)
• ELOVL4 is identified as the causative gene for erythrokeratodermia variabilis and spinocerebellar ataxia in a French-Canadian family. (PMID:24566826)
• A novel homozygous nonsense mutation in ELOVL4 cuases a neuro-ichthyotic disorder with variable expressivity. (PMID:24571530)
• In this review, we summarize our current understanding of the disease-causing mutation and its potential role in STGD3 pathogenesis. (PMID:24664730)
• We propose that transgenic expression of ELOVL4 in the liver will result in the biosynthesis of very long chain-PUFA that can be transported to target. (PMID:24664752)
• In patients with intrahepatic cholestasis of pregnancy, there was no elevation in ELOVL4 mRNA in maternal circulation compared with controls. (PMID:25059952)
• Spinocerebellar ataxia was associated with a novel mutation in ELOVL4 in a large family pedigree. (PMID:26010696)
• Both ELOVL4- and PROM1-related maculopathies are characterized by progressive photoreceptor atrophy and central vision loss. Using advanced diagnostic imaging, early disease changes and disease progression can be characterized. (PMID:26110599)
• different mutations in ELOVL4 can cause variable phenotypic neurological disorders (Review) (PMID:26427403)
• Swiss Family with Dominant Stargardt Disease Caused by a Recurrent Mutation in the ELOVL4 Gene (PMID:27116512)
• In the control group, four different genetic variations were detected in ELOVL4, and five in PRPH2. STGD patients of different ethnicities may carry distinct ELOVL4 and PRPH2 sequence variants. We believe that the genetic variations identified in this study may be related to STGD etiopathogenesis. (PMID:27813578)
• Normalization of retinal ELOVL4 expression could prevent blood-retinal barrier dysregulation in diabetic retinopathy through an increase in very long-chain ceramides and stabilization of tight junctions. (PMID:29362226)
• A highly reduced activity of the ELOVL4 promoter was registered due to combination of two variants. Decrease of ELOVL4 enzymatic activity could lead to a deficiency of VLC-PUFA, essential components for rods function and longevity, which are among the parameters involved in the etiopathogenesis of stargardt disease. (PMID:29417145)
• The Elovl4 Spinocerebellar Ataxia-34 Mutation 736T>G (p.W246G) Impairs Retinal Function in the Absence of Photoreceptor Degeneration. (PMID:32780351)
• Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4. (PMID:33556440)
• Two Italian Patients with ELOVL4-Related Neuro-Ichthyosis: Expanding the Genotypic and Phenotypic Spectrum and Ultrastructural Characterization. (PMID:33652762)
• ELOVL4 with erythrokeratoderma: A pediatric case and emerging genodermatosis. (PMID:33655653)
• The expression of ELOVL4, repressed by MYCN, defines neuroblastoma patients with good outcome. (PMID:34333551)
• Progressive symmetric erythrokeratodermia with spinocerebellar ataxia due to ELOVL4 mutation in a Chinese family. (PMID:34623043)
• Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia. (PMID:34725421)
• ELOVL4 Mutations That Cause Spinocerebellar Ataxia-34 Differentially Alter Very Long Chain Fatty Acid Biosynthesis. (PMID:36464075)
• Two New Families and a Literature Review of ELOVL4-Associated Spinocerebellar Ataxia Type 34. (PMID:36696030)
• Expanding the allelic spectrum of ELOVL4-related autosomal recessive neuro-ichthyosis. (PMID:37592902)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	elovl4a	ENSDARG00000006773
danio_rerio	elovl4b	ENSDARG00000027495
mus_musculus	Elovl4	ENSMUSG00000032262
rattus_norvegicus	Elovl4	ENSRNOG00000009773

Paralogs (6): ELOVL5 (ENSG00000012660), ELOVL1 (ENSG00000066322), ELOVL3 (ENSG00000119915), ELOVL7 (ENSG00000164181), ELOVL6 (ENSG00000170522), ELOVL2 (ENSG00000197977)

Protein

Protein identifiers

Very long chain fatty acid elongase 4 — Q9GZR5 (reviewed: Q9GZR5)

Alternative names: 3-keto acyl-CoA synthase ELOVL4, ELOVL fatty acid elongase 4, Elongation of very long chain fatty acids protein 4, Very long chain 3-ketoacyl-CoA synthase 4, Very long chain 3-oxoacyl-CoA synthase 4

All UniProt accessions (1): Q9GZR5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that catalyzes the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty acids that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May play a critical role in early brain and skin development.

Subunit / interactions. Oligomer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in the retina and at much lower level in the brain. Ubiquitous, highest expression in thymus, followed by testis, small intestine, ovary, and prostate. Little or no expression in heart, lung, liver, or leukocates.

Post-translational modifications. N-glycosylated.

Disease relevance. Stargardt disease 3 (STGD3) [MIM:600110] A form of Stargardt disease, a common hereditary macular degeneration characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD3 is an autosomal dominant form with onset most commonly in the second decade of life. The disease is caused by variants affecting the gene represented in this entry. Ichthyosis, spastic quadriplegia, and impaired intellectual development (ISQMR) [MIM:614457] A severe autosomal recessive disorder characterized by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. The disease is caused by variants affecting the gene represented in this entry. Spinocerebellar ataxia 34 (SCA34) [MIM:133190] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA34 is an autosomal dominant form characterized by the association of progressive cerebellar ataxia with erythrokeratodermia variabilis. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal di-lysine motif confers endoplasmic reticulum localization.

Pathway. Lipid metabolism; fatty acid biosynthesis.

Similarity. Belongs to the ELO family. ELOVL4 subfamily.

RefSeq proteins (1): NP_073563* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002076	ELO_fam	Family
IPR030457	ELO_CS	Conserved_site
IPR033678	ELOVL4	Family

Pfam: PF01151

Catalyzed reactions (Rhea), 12 shown:

• a very-long-chain acyl-CoA + malonyl-CoA + H(+) = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA (RHEA:32727)
• (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + malonyl-CoA + H(+) = (9Z,12Z,15Z,18Z)-3-oxotetracosatetraenoyl-CoA + CO2 + CoA (RHEA:36479)
• tetracosanoyl-CoA + malonyl-CoA + H(+) = 3-oxohexacosanoyl-CoA + CO2 + CoA (RHEA:36515)
• hexacosanoyl-CoA + malonyl-CoA + H(+) = 3-oxooctacosanyol-CoA + CO2 + CoA (RHEA:36519)
• octacosanoyl-CoA + malonyl-CoA + H(+) = 3-oxo-triacontanoyl-CoA + CO2 + CoA (RHEA:36807)
• (11Z,14Z,17Z,20Z,23Z)-hexacosapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(13Z,16Z,19Z,22Z,25Z)-octacosapentaenoyl-CoA + CO2 + CoA (RHEA:36819)
• (13Z,16Z,19Z,22Z,25Z)-octacosapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(15Z,18Z,21Z,24Z,27Z)-triacontapentaenoyl-CoA + CO2 + CoA (RHEA:36843)
• (15Z,18Z,21Z,24Z,27Z)-triacontapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(17Z,20Z,23Z,26Z,29Z)-dotriacontapentaenoyl-CoA + CO2 + CoA (RHEA:36851)
• (17Z,20Z,23Z,26Z,29Z)-dotriacontapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(19Z,22Z,25Z,28Z,31Z)-tetratriacontapentaenoyl-CoA + CO2 + CoA (RHEA:36859)
• (19Z,22Z,25Z,28Z,31Z)-tetratriacontapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(21Z,24Z,27Z,30Z,33Z)-hexatriacontapentaenoyl-CoA + CO2 + CoA (RHEA:36871)
• (21Z,24Z,27Z,30Z,33Z)-hexatriacontapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(23Z,26Z,29Z,32Z,35Z)-octatriacontapentaenoyl-CoA + CO2 + CoA (RHEA:36875)
• (11Z,14Z,17Z,20Z)-hexacosatetraenoyl-CoA + malonyl-CoA + H(+) = (13Z,16Z,19Z,22Z)-3-oxooctacosatetraenoyl-CoA + CO2 + CoA (RHEA:36907)

UniProt features (17 total): transmembrane region 7, sequence variant 3, compositionally biased region 2, chain 1, glycosylation site 1, sequence conflict 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZR5-F1	84.53	0.59

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 20

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs

MSigDB gene sets: 336 (showing top): GOBP_CIRCADIAN_RHYTHM, TGGTGCT_MIR29A_MIR29B_MIR29C, REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, ATGCAGT_MIR217, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, USF_C, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_CELL_CELL_SIGNALING

GO Biological Process (12): fatty acid biosynthetic process (GO:0006633), unsaturated fatty acid biosynthetic process (GO:0006636), fatty acid elongation, saturated fatty acid (GO:0019367), sphingolipid biosynthetic process (GO:0030148), fatty acid elongation, monounsaturated fatty acid (GO:0034625), fatty acid elongation, polyunsaturated fatty acid (GO:0034626), long-chain fatty-acyl-CoA biosynthetic process (GO:0035338), very long-chain fatty acid biosynthetic process (GO:0042761), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), detection of visible light (GO:0009584), fatty acid elongation (GO:0030497)

GO Molecular Function (4): G protein-coupled photoreceptor activity (GO:0008020), fatty acid elongase activity (GO:0009922), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fatty acyl-CoA biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid biosynthetic process	3
lipid biosynthetic process	2
fatty acid elongation, unsaturated fatty acid	2
fatty acid metabolic process	1
monocarboxylic acid biosynthetic process	1
unsaturated fatty acid metabolic process	1
fatty acid elongation	1
sphingolipid metabolic process	1
long-chain fatty-acyl-CoA metabolic process	1
fatty-acyl-CoA biosynthetic process	1
very long-chain fatty acid metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
detection of light stimulus	1
G protein-coupled receptor activity	1
detection of visible light	1
photoreceptor activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELOVL4	IMPG1	Q17R60	978
ELOVL4	TENT5A	Q96IP4	921
ELOVL4	ABCA4	P78363	891
ELOVL4	CNGB3	Q9NQW8	855
ELOVL4	PRPH2	P23942	837
ELOVL4	PROM1	O43490	722
ELOVL4	NSD3	Q9BZ95	649
ELOVL4	CERS3	Q8IU89	639
ELOVL4	BEST1	O76090	600
ELOVL4	FADS2	O95864	590
ELOVL4	PNPLA1	Q8N8W4	581
ELOVL4	CYP4F22	Q6NT55	575
ELOVL4	FADS1	O60427	571
ELOVL4	RIMS1	Q86UR5	534
ELOVL4	SCD	O00767	523

IntAct

307 interactions, top by confidence:

A	B	Type	Score
TECR	ELOVL4	psi-mi:“MI:0915”(physical association)	0.670
ELOVL4	TECR	psi-mi:“MI:0915”(physical association)	0.670
VAMP5	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
BCL2L1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
ADGRE2	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
TF	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
CLDND2	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
ERG28	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
SNORC	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
FAM177A1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
TMEM19	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
GYPA	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
GIMAP1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
SEC22A	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
TMEM42	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (144): ELOVL4 (Affinity Capture-Western), ELOVL4 (Affinity Capture-MS), ELOVL4 (Affinity Capture-MS), ELOVL4 (Affinity Capture-MS), ELOVL4 (Affinity Capture-MS), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid), ELOVL4 (Two-hybrid)

ESM2 similar proteins: A0A0C5PHQ7, A0JNC4, A1L3X0, B4QVX4, D4A612, D4ADY9, G5EEE5, O35949, P49191, Q03574, Q1A3B0, Q1HRV8, Q20300, Q20303, Q2KJD9, Q32NI8, Q3S8M4, Q4D321, Q4D5J7, Q4DHY3, Q4DUK4, Q4QJ85, Q4R516, Q54TC9, Q57UP6, Q57X51, Q5M8U1, Q5RFL5, Q6GLX2, Q6P4N1, Q6PC64, Q84QC0, Q8BHI7, Q8IU89, Q920L5, Q920L6, Q920L7, Q95K73, Q9BW60, Q9D2Y9

Diamond homologs: A0A0C5PHQ7, A0JNC4, A1L3X0, B4QVX4, D4A612, D4ADY9, O35949, P25358, Q1HRV8, Q2KJD9, Q32NI8, Q3S8M4, Q4D321, Q4D5J7, Q4Q5G6, Q4QJ85, Q4R516, Q57X51, Q5M8U1, Q5RFL5, Q8BHI7, Q920L7, Q95K73, Q9BW60, Q9D2Y9, Q9EQC4, Q9GZR5, Q9JLJ4, Q9JLJ5, Q9NXB9, Q9NYP7, Q9VH58, Q9VHX7, P40319, P49191, Q03574, Q54TC9, Q57UP8, Q5ZJR8, Q7LKX0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ELOVL4	“down-regulates quantity”	palmitoyl-CoA	“chemical modification”
ELOVL4	“up-regulates quantity”	3-hydroxyoctadecanoyl-CoA	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	5	38.1×	1e-04
endoplasmic reticulum to Golgi vesicle-mediated transport	7	12.0×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

359 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	8
Uncertain significance	180
Likely benign	99
Benign	34

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1352603	NM_022726.4(ELOVL4):c.436dup (p.Ile146fs)	Pathogenic
143056	NM_022726.4(ELOVL4):c.504G>C (p.Leu168Phe)	Pathogenic
1451876	NM_022726.4(ELOVL4):c.387G>A (p.Trp129Ter)	Pathogenic
1452704	NM_022726.4(ELOVL4):c.435dup (p.Ile146fs)	Pathogenic
1456770	NC_000006.11:g.(?80635891)(80636118_?)del	Pathogenic
1924932	NM_022726.4(ELOVL4):c.600dup (p.Leu201fs)	Pathogenic
2109327	NM_022726.4(ELOVL4):c.425_426del (p.Thr142fs)	Pathogenic
2122250	NM_022726.4(ELOVL4):c.166dup (p.Tyr56fs)	Pathogenic
2703751	NM_022726.4(ELOVL4):c.188del (p.Gly63fs)	Pathogenic
30495	NM_022726.4(ELOVL4):c.690del (p.Ile230fs)	Pathogenic
391976	NM_022726.4(ELOVL4):c.506G>A (p.Trp169Ter)	Pathogenic
430572	NM_022726.4(ELOVL4):c.736T>G (p.Trp246Gly)	Pathogenic
4692951	NM_022726.4(ELOVL4):c.116del (p.Asn39fs)	Pathogenic
4720707	NM_022726.4(ELOVL4):c.426_427del (p.Phe145fs)	Pathogenic
4939	NM_022726.4(ELOVL4):c.790_794del (p.Asn264fs)	Pathogenic
4940	NM_022726.4(ELOVL4):c.789_793delinsAAC (p.Asn264fs)	Pathogenic
561002	NM_022726.4(ELOVL4):c.215del (p.Pro72fs)	Pathogenic
831415	NC_000006.12:g.(?79926194)(79926381_?)del	Pathogenic
1027496	NM_022726.4(ELOVL4):c.571A>T (p.Ile191Phe)	Likely pathogenic
1205363	NM_022726.4(ELOVL4):c.35_48dup (p.Thr17Ter)	Likely pathogenic
2580357	NM_022726.4(ELOVL4):c.541+5G>A	Likely pathogenic
3337077	NM_022726.4(ELOVL4):c.511A>C (p.Ile171Leu)	Likely pathogenic
433192	NM_022726.4(ELOVL4):c.289-2A>G	Likely pathogenic
452923	NM_022726.4(ELOVL4):c.669+1G>A	Likely pathogenic
4808358	NM_022726.4(ELOVL4):c.370-1G>C	Likely pathogenic
809974	NM_022726.4(ELOVL4):c.789dup (p.Asn264Ter)	Likely pathogenic

SpliceAI

1055 predictions. Top by Δscore:

Variant	Effect	Δscore
6:79924946:ACTT:A	donor_loss	1.0000
6:79924947:CTT:C	donor_loss	1.0000
6:79924948:TTA:T	donor_loss	1.0000
6:79924949:TAC:T	donor_loss	1.0000
6:79924950:A:AC	donor_gain	1.0000
6:79924950:AC:A	donor_gain	1.0000
6:79924950:ACCCT:A	donor_loss	1.0000
6:79924951:C:CC	donor_gain	1.0000
6:79924951:C:T	donor_loss	1.0000
6:79924951:CC:C	donor_gain	1.0000
6:79925028:AATAA:A	acceptor_gain	1.0000
6:79925029:ATAA:A	acceptor_gain	1.0000
6:79925029:ATAAC:A	acceptor_loss	1.0000
6:79925030:TAA:T	acceptor_gain	1.0000
6:79925030:TAACT:T	acceptor_loss	1.0000
6:79925031:AA:A	acceptor_gain	1.0000
6:79925031:AACT:A	acceptor_loss	1.0000
6:79925032:AC:A	acceptor_loss	1.0000
6:79925033:C:CC	acceptor_gain	1.0000
6:79925033:CT:C	acceptor_loss	1.0000
6:79925034:T:A	acceptor_loss	1.0000
6:79926193:CCTCT:C	donor_gain	1.0000
6:79926259:T:C	donor_gain	1.0000
6:79926377:CTTAT:C	acceptor_gain	1.0000
6:79926378:TTAT:T	acceptor_gain	1.0000
6:79926379:TAT:T	acceptor_gain	1.0000
6:79926381:TC:T	acceptor_loss	1.0000
6:79926382:C:A	acceptor_loss	1.0000
6:79926382:C:CC	acceptor_gain	1.0000
6:79926383:T:G	acceptor_loss	1.0000

AlphaMissense

2077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:79916767:A:C	F262L	1.000
6:79916767:A:T	F262L	1.000
6:79916769:A:G	F262L	1.000
6:79916782:G:C	S257R	1.000
6:79916782:G:T	S257R	1.000
6:79916784:T:G	S257R	1.000
6:79921685:G:C	H161D	1.000
6:79921761:T:A	K135N	1.000
6:79921761:T:G	K135N	1.000
6:79916758:G:C	F265L	0.999
6:79916758:G:T	F265L	0.999
6:79916760:A:G	F265L	0.999
6:79916875:G:C	F226L	0.999
6:79916875:G:T	F226L	0.999
6:79916876:A:G	F226S	0.999
6:79916877:A:G	F226L	0.999
6:79919444:T:A	K215N	0.999
6:79919444:T:G	K215N	0.999
6:79919449:A:G	W214R	0.999
6:79919449:A:T	W214R	0.999
6:79919490:C:T	G200E	0.999
6:79919513:A:C	H192Q	0.999
6:79919513:A:T	H192Q	0.999
6:79919515:G:C	H192D	0.999
6:79919515:G:T	H192N	0.999
6:79919525:A:C	N188K	0.999
6:79919525:A:T	N188K	0.999
6:79921643:A:G	W175R	0.999
6:79921643:A:T	W175R	0.999
6:79921680:G:C	H162Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000090839 (6:79924459 A>G), RS1000116480 (6:79944578 T>C), RS1000172372 (6:79945027 T>C), RS1000279127 (6:79917084 C>T), RS1000365920 (6:79937970 C>T), RS1000456174 (6:79943075 T>C), RS1000508429 (6:79943345 A>G), RS1000526711 (6:79924768 G>A), RS1000532421 (6:79937098 G>A,C), RS1000805534 (6:79931006 T>A), RS1001015651 (6:79949239 T>A), RS1001105968 (6:79936167 A>G), RS1001150076 (6:79944133 T>C), RS1001220828 (6:79916281 T>C), RS1001479740 (6:79916908 A>G)

Disease associations

OMIM: gene MIM:605512 | disease phenotypes: MIM:133190, MIM:600110, MIM:614457, MIM:108600, MIM:248200

GenCC curated gene-disease

Disease	Classification	Inheritance
Stargardt disease 3	Definitive	Autosomal dominant
congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome	Definitive	Autosomal recessive
spinocerebellar ataxia type 34	Strong	Autosomal dominant
ELOVL4-related maculopathy	Strong	Autosomal dominant
Stargardt disease	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ELOVL4-related maculopathy	Definitive	AD

Mondo (7): spinocerebellar ataxia type 34 (MONDO:0007574), Stargardt disease 3 (MONDO:0010819), congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (MONDO:0013760), spastic ataxia (MONDO:0017845), Stargardt disease (MONDO:0019353), inherited retinal dystrophy (MONDO:0019118), ELOVL4-related maculopathy (MONDO:0700227)

Orphanet (5): Spinocerebellar ataxia type 34 (Orphanet:1955), Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (Orphanet:352333), Stargardt disease (Orphanet:827), Spastic ataxia (Orphanet:316226), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000230	Gingivitis
HP:0000252	Microcephaly
HP:0000324	Facial asymmetry
HP:0000486	Strabismus
HP:0000493	Abnormal foveal morphology
HP:0000505	Visual impairment
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000605	Supranuclear gaze palsy
HP:0000608	Macular degeneration
HP:0000610	Abnormal choroid morphology
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000649	Abnormality of visual evoked potentials
HP:0000662	Nyctalopia
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0001019	Erythroderma
HP:0001025	Urticaria
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000691_5	Partial epilepsies	3.000000e-07
GCST001599_3	Aging	1.000000e-06
GCST002021_9	Body mass index	2.000000e-06
GCST003518_16	Daytime sleep phenotypes	7.000000e-06
GCST003518_47	Daytime sleep phenotypes	4.000000e-06
GCST004147_20	Chronic obstructive pulmonary disease	4.000000e-06
GCST006976_68	Macular thickness	6.000000e-10
GCST012226_482	Waist circumference adjusted for body mass index	4.000000e-11
GCST012228_268	Waist-hip index	7.000000e-10
GCST012230_458	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020028_504	Hip circumference adjusted for BMI	5.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0004340	body mass index
EFO:0007828	daytime rest measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D000080362	Stargardt Disease	C11.270.872; C11.768.585.439.339; C16.320.290.724
C535738	Erythrokeratodermia with ataxia (supp.)
C564815	Spastic Ataxia (supp.)
C535805	Stargardt disease 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169195 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Silicon Dioxide	increases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
urushiol	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	increases expression	1
hydroquinone	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	increases expression	1
Pioglitazone	increases expression	1
Sunitinib	increases expression	1
Aldehydes	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Coal	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5132858	Binding	Inhibition of ELOVL4 (unknown origin) in presence of C26-acyl-CoA by radiometric enzyme assay	Discovery and Optimization of Pyrazole Amides as Inhibitors of ELOVL1. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1VY	HAP1 ELOVL4 (-) 1	Cancer cell line	Male
CVCL_E1VZ	HAP1 ELOVL4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

86 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
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
NCT07419334	PHASE3	RECRUITING	Study of ALK-001 on the Progression of Stargardt Disease
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT02402660	PHASE2	ENROLLING_BY_INVITATION	Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease
NCT03033108	PHASE2	COMPLETED	Pharmacodynamic Study of Emixustat Hydrochloride in Subjects With Macular Atrophy Secondary to Stargardt Disease
NCT04239625	PHASE2	ACTIVE_NOT_RECRUITING	Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt Disease (TEASE)
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in 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
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
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
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
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04281732	Not specified	UNKNOWN	Visual Performance Measures in a Virtual Reality Environment for Assessing Clinical Trial Outcomes in Those With Severely Reduced Vision
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
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
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
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
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
NCT02255981	Not specified	COMPLETED	Efficacy of Acupuncture in Macular Diseases
NCT02410122	Not specified	COMPLETED	The Natural History of the Progression of Atrophy Secondary to Stargardt Disease Type 4: PROM1-Related Macular Dystrophy
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02875704	Not specified	TERMINATED	Oxidative Stress In Stargardt Disease, Age Related Macular Degeneration and Diabetic Retinopathy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT03297515	Not specified	COMPLETED	Therapeutic Potential of Omega-3 Fatty Acids Supplementation in Dry Macular Degeneration and Stargardt Disease