ELOVL5

Summary

ELOVL5 (ELOVL fatty acid elongase 5, HGNC:21308) is a protein-coding gene on chromosome 6p12.1, encoding Very long chain fatty acid elongase 5 (Q9NYP7). Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.

This gene belongs to the ELO family. It is highly expressed in the adrenal gland and testis, and encodes a multi-pass membrane protein that is localized in the endoplasmic reticulum. This protein is involved in the elongation of long-chain polyunsaturated fatty acids. Mutations in this gene have been associated with spinocerebellar ataxia-38 (SCA38). Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 60481 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 38 (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 172 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_021814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21308
Approved symbol	ELOVL5
Name	ELOVL fatty acid elongase 5
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	HELO1, dJ483K16.1
Ensembl gene	ENSG00000012660
Ensembl biotype	protein_coding
OMIM	611805
Entrez	60481

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000304434, ENST00000370913, ENST00000370918, ENST00000465983, ENST00000485336, ENST00000486973, ENST00000542638, ENST00000893711, ENST00000893712, ENST00000893713, ENST00000893714, ENST00000893715, ENST00000893716, ENST00000893717, ENST00000893718, ENST00000893719, ENST00000893720, ENST00000893721, ENST00000893722, ENST00000926653, ENST00000926654, ENST00000926655, ENST00000926656, ENST00000926657, ENST00000954545, ENST00000954546, ENST00000954547, ENST00000954548

RefSeq mRNA: 5 — MANE Select: NM_021814 NM_001242828, NM_001242830, NM_001242831, NM_001301856, NM_021814

CCDS: CCDS4951, CCDS56433, CCDS56434, CCDS75470

Canonical transcript exons

ENST00000304434 — 8 exons

Exon	Start	End
ENSE00001137509	53273220	53273344
ENSE00001137513	53275090	53275261
ENSE00001934663	53348817	53348950
ENSE00001943624	53267404	53269270
ENSE00003477967	53291776	53291963
ENSE00003531793	53276179	53276256
ENSE00003657861	53295642	53295707
ENSE00003732002	53270593	53270727

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 122.9175 / max 1141.6646, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74010	120.4698	1823
74011	2.4476	1400

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	99.34	gold quality
secondary oocyte	CL:0000655	99.27	gold quality
mammary duct	UBERON:0001765	99.02	gold quality
tibia	UBERON:0000979	98.94	gold quality
upper leg skin	UBERON:0004262	98.93	gold quality
mammary gland	UBERON:0001911	98.92	gold quality
thoracic mammary gland	UBERON:0005200	98.92	gold quality
epithelium of mammary gland	UBERON:0003244	98.91	gold quality
trigeminal ganglion	UBERON:0001675	98.84	gold quality
epithelium of nasopharynx	UBERON:0001951	98.80	gold quality
parietal pleura	UBERON:0002400	98.80	gold quality
adrenal tissue	UBERON:0018303	98.75	gold quality
dorsal root ganglion	UBERON:0000044	98.72	gold quality
inferior vagus X ganglion	UBERON:0005363	98.68	gold quality
pigmented layer of retina	UBERON:0001782	98.66	gold quality
cartilage tissue	UBERON:0002418	98.63	gold quality
pleura	UBERON:0000977	98.55	gold quality
pericardium	UBERON:0002407	98.54	gold quality
middle frontal gyrus	UBERON:0002702	98.52	gold quality
thymus	UBERON:0002370	98.42	gold quality
medulla oblongata	UBERON:0001896	98.40	gold quality
superior vestibular nucleus	UBERON:0007227	98.37	gold quality
visceral pleura	UBERON:0002401	98.32	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.32	gold quality
subthalamic nucleus	UBERON:0001906	98.30	gold quality
right adrenal gland cortex	UBERON:0035827	98.30	gold quality
pons	UBERON:0000988	98.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.29	gold quality
trabecular bone tissue	UBERON:0002483	98.27	gold quality
right adrenal gland	UBERON:0001233	98.26	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2418.40
E-MTAB-10885	yes	492.72
E-MTAB-7381	no	288.10
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, NR1H3, PPARA, SREBF1

miRNA regulators (miRDB)

123 targeting ELOVL5, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3065-3P	99.87	70.25	1407

Literature-anchored findings (GeneRIF, showing 16)

• Our genome-wide association study identified SRBD1 and ELOVL5 as new susceptibility genes for (normal tension glaucoma) NTG. (PMID:20363506)
• Not being breastfed resulted in a disadvantage in cognition (5 to 8 points) among children CC homozygote for rs2397142 (low ELOVL5 activity), but not among those carrying the G allele. (PMID:21383846)
• Typical POAG associated with ELOVL5 gene polymorphism may have a late rather than an early onset. (PMID:21508110)
• minor allele copies at rs2294867 associated with an increase in total and LDL cholesterol…number of minor allele copies at rs761179 associated with increase in total cholesterol… However, associations not replicated in independent populations. (PMID:22293571)
• a novel link between Elovl5-mediated synthesis of 18:1,n-7 and GNG through the control of the mTORC2-Akt-FoxO1 pathway (PMID:23099444)
• Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children. (PMID:24167612)
• In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. (PMID:25065913)
• performed a detailed promoter/enhancer analysis of ELOVL5 gene, and identified two new SREBP binding sites, one in the 10 kb upstream region and one in the exon 1 (PMID:26321664)
• SCA38 subtype is very rare in Mainland China; no disease-related gene mutations in ELOVL5. (PMID:26433464)
• common variations associated with polyunsaturated fatty acid levels in breast milk (PMID:28245901)
• Low ELOVL5 expression is associated with colorectal cancer. (PMID:28931069)
• The ELOVL5 gene was significantly differentially expressed in adipose tissues from unrelated type 2 diabetes (T2D) patients and in human pancreatic islets. The results demonstrate that blood-derived DNA methylation is associated with T2D risk as a proxy for cumulative epigenetic status in human adipose and pancreatic tissues. (PMID:30291282)
• The that maternal genetic variants in ELOVL2 and ELOVL5 were associated with PUFA levels in breast milk and that the combination of SNP haplotypes and higher DHA intake increased PUFA concentrations. (PMID:30914501)
• ELOVL5 Is a Critical and Targetable Fatty Acid Elongase in Prostate Cancer. (PMID:33547161)
• ELOVL5-mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma. (PMID:35670054)
• Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-beta receptors. (PMID:36056008)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	elovl5	ENSDARG00000004979
mus_musculus	Elovl5	ENSMUSG00000032349
rattus_norvegicus	Elovl5	ENSRNOG00000006331

Paralogs (6): ELOVL1 (ENSG00000066322), ELOVL4 (ENSG00000118402), ELOVL3 (ENSG00000119915), ELOVL7 (ENSG00000164181), ELOVL6 (ENSG00000170522), ELOVL2 (ENSG00000197977)

Protein

Protein identifiers

Very long chain fatty acid elongase 5 — Q9NYP7 (reviewed: Q9NYP7)

Alternative names: 3-keto acyl-CoA synthase ELOVL5, ELOVL fatty acid elongase 5, Elongation of very long chain fatty acids protein 5, Fatty acid elongase 1, Very long chain 3-ketoacyl-CoA synthase 5, Very long chain 3-oxoacyl-CoA synthase 5

All UniProt accessions (2): Q9NYP7, A0A0A0MTI6

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 acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA. May participate in the production of monounsaturated and of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. In conditions where the essential linoleic and alpha linoleic fatty acids are lacking it is also involved in the synthesis of Mead acid from oleic acid.

Subunit / interactions. Interacts with TECR.

Subcellular location. Endoplasmic reticulum membrane. Cell projection. Dendrite.

Tissue specificity. Ubiquitous. Highly expressed in the adrenal gland and testis. Weakly expressed in prostate, lung and brain. Expressed in the cerebellum.

Disease relevance. Spinocerebellar ataxia 38 (SCA38) [MIM:615957] 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. SCA38 is an autosomal dominant form characterized by adult-onset of slowly progressive gait ataxia accompanied by nystagmus. Brain MRI shows cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; polyunsaturated fatty acid biosynthesis.

Similarity. Belongs to the ELO family. ELOVL5 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NYP7-1	1	yes
Q9NYP7-2	2
Q9NYP7-3	3

RefSeq proteins (5): NP_001229757, NP_001229759, NP_001229760, NP_001288785, NP_068586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002076	ELO_fam	Family
IPR033677	ELOVL5	Family

Pfam: PF01151

Catalyzed reactions (Rhea), 10 shown:

• a very-long-chain acyl-CoA + malonyl-CoA + H(+) = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA (RHEA:32727)
• (6Z,9Z,12Z)-octadecatrienoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(8Z,11Z,14Z)-eicosatrienoyl-CoA + CO2 + CoA (RHEA:35379)
• (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA + CO2 + CoA (RHEA:35391)
• (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + malonyl-CoA + H(+) = (7Z,10Z,13Z,16Z)-3-oxodocosatetraenoyl-CoA + CO2 + CoA (RHEA:36475)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA + CO2 + CoA (RHEA:36483)
• (9Z,12Z)-octadecadienoyl-CoA + malonyl-CoA + H(+) = (11Z,14Z)-3-oxoicosa-11,14-dienoyl-CoA + CO2 + CoA (RHEA:36503)
• (9Z)-octadecenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(11Z)-eicosenoyl-CoA + CO2 + CoA (RHEA:36511)
• (9Z,12Z,15Z)-octadecatrienoyl-CoA + malonyl-CoA + H(+) = (11Z,14Z,17Z)-3-oxoeicosatrienoyl-CoA + CO2 + CoA (RHEA:36523)
• (9Z)-hexadecenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(11Z)-octadecenoyl-CoA + CO2 + CoA (RHEA:39675)
• (11Z)-octadecenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(13Z)-eicosenoyl-CoA + CO2 + CoA (RHEA:39679)

UniProt features (21 total): transmembrane region 7, sequence conflict 4, splice variant 3, modified residue 2, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYP7-F1	82.53	0.48

Functional residue map

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

Post-translational modifications (2): 1, 285

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2046105	Linoleic acid (LA) metabolism
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis

MSigDB gene sets: 412 (showing top): ATF_B, RNGTGGGC_UNKNOWN, REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, YANG_BREAST_CANCER_ESR1_BULK_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, SREBP1_02

GO Biological Process (16): 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), alpha-linolenic acid metabolic process (GO:0036109), long-chain fatty acid biosynthetic process (GO:0042759), very long-chain fatty acid biosynthetic process (GO:0042761), linoleic acid metabolic process (GO:0043651), positive regulation of fatty acid biosynthetic process (GO:0045723), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), fatty acid elongation (GO:0030497), fatty acid derivative biosynthetic process (GO:1901570)

GO Molecular Function (3): fatty acid elongase activity (GO:0009922), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (7): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body (GO:0043025), dendritic tree (GO:0097447), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	2
Fatty acyl-CoA biosynthesis	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid biosynthetic process	5
unsaturated fatty acid metabolic process	3
lipid biosynthetic process	3
long-chain fatty acid metabolic process	3
fatty acid elongation, unsaturated fatty acid	2
olefinic compound metabolic process	2
cellular anatomical structure	2
neuron projection	2
somatodendritic compartment	2
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
regulation of fatty acid biosynthetic process	1
positive regulation of fatty acid metabolic process	1
positive regulation of lipid biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
monocarboxylic acid biosynthetic process	1
fatty acid derivative metabolic process	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
dendritic tree	1
cell body	1
dendrite	1

Protein interactions and networks

STRING

1908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELOVL5	FADS2	O95864	818
ELOVL5	FADS1	O60427	817
ELOVL5	SCD	O00767	759
ELOVL5	FASN	P49327	674
ELOVL5	SREBF1	P36956	655
ELOVL5	ACACA	Q13085	629
ELOVL5	KLF14	Q8TD94	612
ELOVL5	SCD5	Q86SK9	604
ELOVL5	FHL2	Q14192	603
ELOVL5	GPAM	Q9HCL2	595
ELOVL5	SP6	Q3SY56	585
ELOVL5	TRIM59	Q8IWR1	580
ELOVL5	AASDH	Q4L235	576
ELOVL5	SRBD1	Q8N5C6	571
ELOVL5	PPARA	Q07869	565

IntAct

90 interactions, top by confidence:

A	B	Type	Score
TECR	HACD2	psi-mi:“MI:0914”(association)	0.850
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TECR	HACD1	psi-mi:“MI:0914”(association)	0.700
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
NINJ2	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
PLP2	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
STX7	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
SLC39A9	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
TSNARE1	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
C2CD2L	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
ELOVL5	NINJ2	psi-mi:“MI:0915”(physical association)	0.560
SYS1	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
HMOX2	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
TMEM243	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
ELOVL5	THSD7A	psi-mi:“MI:0915”(physical association)	0.560
SYNJ2BP	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (386): ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Reconstituted Complex), ELOVL5 (Affinity Capture-MS), ROMO1 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ELOVL5 (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
ELOVL5	“down-regulates quantity”	palmitoyl-CoA	“chemical modification”
ELOVL5	“up-regulates quantity”	3-hydroxyoctadecanoyl-CoA	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	92
Likely benign	30
Benign	28

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
144075	NM_021814.5(ELOVL5):c.689G>T (p.Gly230Val)	Pathogenic
144076	NM_021814.5(ELOVL5):c.214C>G (p.Leu72Val)	Pathogenic
1676306	GRCh37/hg19 6p21.1-q12(chr6:43636308-64947206)x3	Likely pathogenic

SpliceAI

1757 predictions. Top by Δscore:

Variant	Effect	Δscore
6:53269271:C:CC	acceptor_gain	1.0000
6:53269276:A:AC	acceptor_gain	1.0000
6:53269278:G:C	acceptor_gain	1.0000
6:53269278:G:GC	acceptor_gain	1.0000
6:53275086:TTA:T	donor_loss	1.0000
6:53275087:TACA:T	donor_loss	1.0000
6:53275088:A:AC	donor_gain	1.0000
6:53275088:ACA:A	donor_loss	1.0000
6:53275089:C:CA	donor_gain	1.0000
6:53275089:CA:C	donor_gain	1.0000
6:53275089:CAG:C	donor_gain	1.0000
6:53275121:C:CT	donor_gain	1.0000
6:53275262:C:CC	acceptor_gain	1.0000
6:53276253:CTAA:C	acceptor_gain	1.0000
6:53276257:C:CC	acceptor_gain	1.0000
6:53294404:T:TA	donor_gain	1.0000
6:53295705:AACC:A	acceptor_loss	1.0000
6:53295706:ACCT:A	acceptor_loss	1.0000
6:53295707:CCT:C	acceptor_loss	1.0000
6:53295708:C:A	acceptor_loss	1.0000
6:53295709:T:A	acceptor_loss	1.0000
6:53269266:TAGGT:T	acceptor_gain	0.9900
6:53269268:GGT:G	acceptor_gain	0.9900
6:53269269:GTCTA:G	acceptor_loss	0.9900
6:53269270:TC:T	acceptor_loss	0.9900
6:53269271:CTAA:C	acceptor_loss	0.9900
6:53269276:A:C	acceptor_gain	0.9900
6:53269280:G:C	acceptor_gain	0.9900
6:53269280:G:GC	acceptor_gain	0.9900
6:53273219:CCAG:C	donor_gain	0.9900

AlphaMissense

1971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:53270611:G:C	F246L	1.000
6:53270611:G:T	F246L	1.000
6:53270613:A:G	F246L	1.000
6:53275150:G:C	H146D	1.000
6:53275226:T:A	K120N	1.000
6:53275226:T:G	K120N	1.000
6:53270602:G:C	F249L	0.999
6:53270602:G:T	F249L	0.999
6:53270604:A:G	F249L	0.999
6:53270719:A:C	F210L	0.999
6:53270719:A:T	F210L	0.999
6:53270721:A:G	F210L	0.999
6:53273249:A:G	W198R	0.999
6:53273249:A:T	W198R	0.999
6:53273310:G:C	H177Q	0.999
6:53273310:G:T	H177Q	0.999
6:53273312:G:C	H177D	0.999
6:53273312:G:T	H177N	0.999
6:53273319:G:C	S174R	0.999
6:53273319:G:T	S174R	0.999
6:53273321:T:G	S174R	0.999
6:53273322:A:C	N173K	0.999
6:53273322:A:T	N173K	0.999
6:53275145:A:C	H147Q	0.999
6:53275145:A:T	H147Q	0.999
6:53275147:G:C	H147D	0.999
6:53275147:G:T	H147N	0.999
6:53275148:G:C	H146Q	0.999
6:53275148:G:T	H146Q	0.999
6:53275150:G:T	H146N	0.999

dbSNP variants (sampled 300 via entrez): RS1000024861 (6:53298349 T>C), RS1000045612 (6:53286382 G>A), RS1000050067 (6:53313341 T>A), RS1000207137 (6:53319120 A>C), RS1000213513 (6:53325002 T>C,G), RS1000226322 (6:53318907 T>C), RS1000258901 (6:53318651 G>C), RS1000265514 (6:53325134 T>C), RS1000294992 (6:53268567 A>G), RS1000297555 (6:53306896 G>A), RS1000373467 (6:53267345 G>GGATT), RS1000410781 (6:53268985 T>C), RS1000457327 (6:53331095 C>G,T), RS1000468622 (6:53289858 C>T), RS1000520921 (6:53289562 T>C,G)

Disease associations

OMIM: gene MIM:611805 | disease phenotypes: MIM:615957

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 38	Strong	Autosomal dominant

Mondo (2): spinocerebellar ataxia type 38 (MONDO:0014417), myoepithelial tumor (MONDO:0002380)

Orphanet (1): Spinocerebellar ataxia type 38 (Orphanet:423296)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000514	Slow saccadic eye movements
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002460	Distal muscle weakness
HP:0003474	Somatic sensory dysfunction
HP:0003477	Peripheral axonal neuropathy
HP:0003596	Middle age onset
HP:0003677	Slowly progressive
HP:0006855	Cerebellar vermis atrophy
HP:0007366	Atrophy/Degeneration affecting the brainstem
HP:0009830	Peripheral neuropathy
HP:0011462	Young adult onset

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000645_2	Glaucoma	4.000000e-06
GCST003072_3	Cerebrospinal fluid AB1-42 levels	8.000000e-07
GCST003230_1	Survival in colorectal cancer (distant metastatic)	4.000000e-09
GCST003230_3	Survival in colorectal cancer (distant metastatic)	8.000000e-10
GCST003518_85	Daytime sleep phenotypes	4.000000e-06
GCST006088_47	Familial squamous cell lung carcinoma	5.000000e-06
GCST009391_226	Metabolite levels	6.000000e-06
GCST90002388_95	Lymphocyte count	3.000000e-12
GCST90002395_480	Mean platelet volume	2.000000e-12
GCST90002396_328	Mean reticulocyte volume	4.000000e-37
GCST90002397_467	Mean spheric corpuscular volume	4.000000e-12
GCST90002404_264	Red cell distribution width	9.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0000714	survival time
EFO:0007675	metastasis measurement
EFO:0007828	daytime rest measurement
EFO:0006953	family history of lung cancer
EFO:0010491	glycocholate measurement
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5937 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.54	Kd	2869	nM	CHEMBL3752910
5.54	ED50	2869	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148316: Binding affinity to human ELOVL5 incubated for 45 mins by Kinobead based pull down assay	kd	2.8691	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, affects methylation	3
bisphenol A	increases expression, affects cotreatment, increases methylation	2
Fulvestrant	increases methylation, decreases expression, affects cotreatment	2
Aspirin	decreases expression, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
afimoxifene	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
di-n-hexyl phthalate	decreases expression	1
hydroquinone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007920	Binding	Inhibition of human ELOVL5 expressed in african green monkey COS7 cells	Synthesis and evaluation of a novel indoledione class of long chain fatty acid elongase 6 (ELOVL6) inhibitors. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 finite cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0I0	GM28024	Finite cell line	Female
CVCL_B1R1	Abcam HeLa ELOVL5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT03109626	Not specified	COMPLETED	Docosahexaenoic Acid (DHA) Replacement for Treatment in Spinocerebellar Ataxia 38
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis