ELOVL2

Summary

ELOVL2 (ELOVL fatty acid elongase 2, HGNC:14416) is a protein-coding gene on chromosome 6p24.2, encoding Very long chain fatty acid elongase 2 (Q9NXB9). Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.

Enables fatty acid elongase activity. Involved in fatty acid elongation, polyunsaturated fatty acid and very long-chain fatty acid biosynthetic process. Located in endoplasmic reticulum.

Source: NCBI Gene 54898 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• MANE Select transcript: NM_017770

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14416
Approved symbol	ELOVL2
Name	ELOVL fatty acid elongase 2
Location	6p24.2
Locus type	gene with protein product
Status	Approved
Aliases	Ssc2
Ensembl gene	ENSG00000197977
Ensembl biotype	protein_coding
OMIM	611814
Entrez	54898

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000354666, ENST00000854792, ENST00000854793, ENST00000854794, ENST00000912166, ENST00000912167

RefSeq mRNA: 1 — MANE Select: NM_017770 NM_017770

CCDS: CCDS4518

Canonical transcript exons

ENST00000354666 — 8 exons

Exon	Start	End
ENSE00000516985	10990318	10990442
ENSE00000684819	10989703	10989837
ENSE00000684874	10995007	10995178
ENSE00000684876	11000087	11000164
ENSE00000684877	11005372	11005559
ENSE00000684878	11010746	11010809
ENSE00001009141	11044228	11044305
ENSE00001481183	10980759	10983906

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 95.68.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7128 / max 107.4302, expressed in 546 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71704	2.3693	487
71706	0.1955	94
71705	0.1479	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.68	gold quality
ganglionic eminence	UBERON:0004023	94.09	gold quality
pigmented layer of retina	UBERON:0001782	87.78	gold quality
inferior olivary complex	UBERON:0002127	87.46	gold quality
paraflocculus	UBERON:0005351	87.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.70	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.62	gold quality
spinal cord	UBERON:0002240	85.42	gold quality
cortical plate	UBERON:0005343	85.39	gold quality
CA1 field of hippocampus	UBERON:0003881	84.36	gold quality
placenta	UBERON:0001987	84.33	gold quality
middle frontal gyrus	UBERON:0002702	83.92	gold quality
liver	UBERON:0002107	83.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.56	gold quality
entorhinal cortex	UBERON:0002728	82.88	gold quality
embryo	UBERON:0000922	82.74	gold quality
frontal pole	UBERON:0002795	82.66	gold quality
caudate nucleus	UBERON:0001873	82.45	gold quality
endothelial cell	CL:0000115	82.44	gold quality
postcentral gyrus	UBERON:0002581	82.42	gold quality
nucleus accumbens	UBERON:0001882	82.41	gold quality
secondary oocyte	CL:0000655	81.46	gold quality
superior frontal gyrus	UBERON:0002661	81.34	gold quality
putamen	UBERON:0001874	80.90	gold quality
temporal lobe	UBERON:0001871	80.59	gold quality
amygdala	UBERON:0001876	80.27	gold quality
right lobe of liver	UBERON:0001114	79.83	gold quality
parietal lobe	UBERON:0001872	79.77	gold quality
corpus callosum	UBERON:0002336	79.76	gold quality
telencephalon	UBERON:0001893	79.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.16
E-MTAB-5061	no	3.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

167 targeting ELOVL2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642

Literature-anchored findings (GeneRIF, showing 26)

• rs3756963 in ELOVL2 gene may be associated with paranoid schizophrenia. (PMID:21560298)
• gene interaction analysis showed that the combined genotype of FADS1 rs174556 (T/T) and ELOVL2 rs3756963 (T/T) was weakly associated with coronary artery disease (PMID:21917437)
• Methylation of ELOVL2 gene is a new epigenetic marker of age. (PMID:23061750)
• we do not found the association between rs3756593 of ELOVL2 gene and acute coronary syndrome in Chinese Han population (PMID:23555103)
• results show that the ELOVL2 locus provides a very good source of information about human chronological age based on analysis of blood, including bloodstains, and it may constitute a powerful and reliable predictor in future forensic age estimation models (PMID:25450787)
• Polymorphisms in the ELOVL2 gene were not associated with the risk of developing allergic disease (PMID:26633493)
• ELOVL2 methylation is a marker of cell divisions occurring during human aging (PMID:27672102)
• Estrogen Enhances the Expression of the Polyunsaturated Fatty Acid Elongase Elovl2 via ERalpha in Breast Cancer Cells (PMID:27788154)
• common variations not associated with polyunsaturated fatty acid levels in breast milk (PMID:28245901)
• Results shows that ELOVL2 promoter displays an exceptionally consistent increase in DNA methylation with age in all tissues. (PMID:29848354)
• Evidence of an association between ELOVL2 (and FADS2) polymorphisms and autism spectrum disorder susceptibility was found in Chinese children. (PMID:30180836)
• Study identified two independent SNPs of ELOVL2 rs3734398 T>C and HSD17B12 rs11037684 A>G that predicted cutaneous melanoma disease-specific survival. The ELOVL2 rs3734398 variant CC genotype was found to be associated with a significantly increased mRNA expression level. (PMID:30734280)
• 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)
• Fibroblasts mirror the established DNA methylation (DNAm) topology of the age-related ELOVL2 gene in human blood and the rapid hypermethylation of its promoter cg16867657, which correlates with a linear decrease in ELOVL2 mRNA levels across the lifespan. (PMID:31156022)
• Findings indicate that superenhancer element drives expression of ELOVL2, with contributions from the stem state-specific transcription factor SOX2. Also, ELOVL2 is critical for the maintenance of glioma stem cells. (PMID:31201181)
• he tumor suppressive properties of DHA and ELOVL2 are repressed by the MYCN and PRC1 jointly, which suggests a new epigenetic mechanism of MYCN-mediated fatty acid regulation and indicates PRC1 inhibition as a potential novel strategy to activate ELOVL2 suppressive functions. (PMID:31856871)
• FADS1 and ELOVL2 polymorphisms reveal associations for differences in lipid metabolism in a cross-sectional population-based survey of Brazilian men and women. (PMID:32502762)
• Association Between Genetic Variants in FADS1-FADS2 and ELOVL2 and Obesity, Lipid Traits, and Fatty Acids in Tunisian Population. (PMID:32584610)
• Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer’s disease in the Tunisian population. (PMID:32682282)
• Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity. (PMID:32843713)
• Improvements and inter-laboratory implementation and optimization of blood-based single-locus age prediction models using DNA methylation of the ELOVL2 promoter. (PMID:32973211)
• Higher Increase in Plasma DHA in Females Compared to Males Following EPA Supplementation May Be Influenced by a Polymorphism in ELOVL2: An Exploratory Study. (PMID:33174255)
• ELOVL2 promotes cancer progression by inhibiting cell apoptosis in renal cell carcinoma. (PMID:34841437)
• ELOVL2 restrains cell proliferation, migration, and invasion of prostate cancer via regulation of the tumor suppressor INPP4B. (PMID:35640821)
• An ELOVL2-Based Epigenetic Clock for Forensic Age Prediction: A Systematic Review. (PMID:36768576)
• ELOVL2-methylation and renal and cardiovascular event in patients with chronic kidney disease. (PMID:37493252)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	elovl2	ENSDARG00000045414
mus_musculus	Elovl2	ENSMUSG00000021364
rattus_norvegicus	Elovl2	ENSRNOG00000014702

Paralogs (6): ELOVL5 (ENSG00000012660), ELOVL1 (ENSG00000066322), ELOVL4 (ENSG00000118402), ELOVL3 (ENSG00000119915), ELOVL7 (ENSG00000164181), ELOVL6 (ENSG00000170522)

Protein

Protein identifiers

Very long chain fatty acid elongase 2 — Q9NXB9 (reviewed: Q9NXB9)

Alternative names: 3-keto acyl-CoA synthase ELOVL2, ELOVL fatty acid elongase 2, Elongation of very long chain fatty acids protein 2, Very long chain 3-ketoacyl-CoA synthase 2, Very long chain 3-oxoacyl-CoA synthase 2

All UniProt accessions (1): Q9NXB9

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 polyunsaturated very long chain fatty acid (C20- and C22-PUFA), acting specifically toward polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA. May participate in the production of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.

Subunit / interactions. Interacts with TECR.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Liver and testis.

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

Pathway. Lipid metabolism; polyunsaturated fatty acid biosynthesis.

Similarity. Belongs to the ELO family. ELOVL2 subfamily.

RefSeq proteins (1): NP_060240* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002076	ELO_fam	Family
IPR030457	ELO_CS	Conserved_site
IPR033680	ELOVL2	Family

Pfam: PF01151

Catalyzed reactions (Rhea), 5 shown:

• a very-long-chain acyl-CoA + malonyl-CoA + H(+) = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA (RHEA:32727)
• (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + malonyl-CoA + H(+) = (7Z,10Z,13Z,16Z)-3-oxodocosatetraenoyl-CoA + CO2 + CoA (RHEA:36475)
• (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + malonyl-CoA + H(+) = (9Z,12Z,15Z,18Z)-3-oxotetracosatetraenoyl-CoA + CO2 + CoA (RHEA:36479)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + malonyl-CoA + H(+) = 3-oxo-(7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA + CO2 + CoA (RHEA:36483)
• (7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA + malonyl-CoA + H(+) = (9Z,12Z,15Z,18Z,21Z)-3-oxotetracosapentaenoyl-CoA + CO2 + CoA (RHEA:36491)

UniProt features (13 total): transmembrane region 7, sequence variant 2, sequence conflict 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXB9-F1	87.30	0.77

Function

Pathways and Gene Ontology

Reactome pathways

3 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

MSigDB gene sets: 219 (showing top): REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_255, chr6p24, AAGCCAT_MIR135A_MIR135B, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

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), very long-chain fatty acid metabolic process (GO:0000038), 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 (4): fatty acid elongase activity (GO:0009922), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	2
Fatty acyl-CoA biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid biosynthetic process	4
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
fatty acid metabolic process	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
primary metabolic process	1
lipid metabolic process	1
monocarboxylic 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
acyltransferase 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

1546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELOVL2	AWAT1	Q58HT5	866
ELOVL2	DGAT2	Q96PD7	842
ELOVL2	FADS2	O95864	756
ELOVL2	FADS1	O60427	756
ELOVL2	KLF14	Q8TD94	668
ELOVL2	FHL2	Q14192	665
ELOVL2	FABP4	P15090	664
ELOVL2	SCD	O00767	650
ELOVL2	SP6	Q3SY56	624
ELOVL2	TRIM59	Q8IWR1	610
ELOVL2	EDARADD	Q8WWZ3	581
ELOVL2	PDE4C	Q08493	580
ELOVL2	CCDC102B	Q68D86	570
ELOVL2	ELOVL3	Q9HB03	553
ELOVL2	SYCP2L	Q5T4T6	544

IntAct

48 interactions, top by confidence:

A	B	Type	Score
TECR	HACD2	psi-mi:“MI:0914”(association)	0.850
TECR	HACD1	psi-mi:“MI:0914”(association)	0.700
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
MALL	ELOVL2	psi-mi:“MI:0915”(physical association)	0.560
FXYD6	ELOVL2	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	ELOVL2	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	ELOVL2	psi-mi:“MI:0915”(physical association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
ELOVL2	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
VIPR2	C15orf61	psi-mi:“MI:0914”(association)	0.350
FPR2	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.350
TRIM13	CKAP4	psi-mi:“MI:0914”(association)	0.350
AVPR2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CACNG1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TSPAN10	KLRG2	psi-mi:“MI:0914”(association)	0.350
C5AR1	TCAF2	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
VIPR2	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
CMKLR1	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): ELOVL2 (Affinity Capture-MS), ELOVL2 (Affinity Capture-MS), ELOVL2 (Affinity Capture-MS), ELOVL2 (Affinity Capture-MS), ELOVL2 (Affinity Capture-MS), ELOVL2 (Affinity Capture-MS), ELOVL2 (Affinity Capture-MS), ELOVL2 (Affinity Capture-MS), ELOVL2 (Two-hybrid), ELOVL2 (Two-hybrid), ELOVL2 (Two-hybrid), ELOVL2 (Two-hybrid), ELOVL2 (Proximity Label-MS), ELOVL2 (Proximity Label-MS), ELOVL2 (Proximity Label-MS)

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
ELOVL2	“down-regulates quantity”	palmitoyl-CoA	“chemical modification”
ELOVL2	“up-regulates quantity”	3-hydroxyoctadecanoyl-CoA	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (q) signalling events	5	10.2×	3e-03
G alpha (i) signalling events	5	7.0×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
phospholipase C-activating G protein-coupled receptor signaling pathway	5	17.8×	3e-04
positive regulation of cytosolic calcium ion concentration	5	15.8×	4e-04
G protein-coupled receptor signaling pathway	8	7.8×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2004 predictions. Top by Δscore:

Variant	Effect	Δscore
6:10983925:T:C	acceptor_gain	1.0000
6:10983925:T:TC	acceptor_gain	1.0000
6:10989735:A:AC	donor_gain	1.0000
6:10989736:C:CC	donor_gain	1.0000
6:10990317:CCAG:C	donor_gain	1.0000
6:11000178:A:T	acceptor_gain	1.0000
6:11044224:TCA:T	donor_loss	1.0000
6:11044225:CACCA:C	donor_loss	1.0000
6:11044226:A:AC	donor_gain	1.0000
6:11044226:A:AG	donor_loss	1.0000
6:11044227:C:A	donor_loss	1.0000
6:11044227:C:CC	donor_gain	1.0000
6:10983916:G:C	acceptor_gain	0.9900
6:10983918:G:C	acceptor_gain	0.9900
6:10983920:A:C	acceptor_gain	0.9900
6:10983923:T:TC	acceptor_gain	0.9900
6:10988767:T:TA	donor_gain	0.9900
6:10989768:A:AT	donor_gain	0.9900
6:11000177:C:CT	acceptor_gain	0.9900
6:11005501:A:T	acceptor_gain	0.9900
6:11010674:AATC:A	donor_gain	0.9900
6:11010703:T:TA	donor_gain	0.9900
6:11010807:TTCCT:T	acceptor_loss	0.9900
6:11010808:TCCT:T	acceptor_loss	0.9900
6:11010809:CCT:C	acceptor_loss	0.9900
6:11010810:C:CA	acceptor_loss	0.9900
6:11010810:C:CC	acceptor_gain	0.9900
6:11010811:T:G	acceptor_loss	0.9900
6:11044226:AC:A	donor_gain	0.9900
6:11044227:CC:C	donor_gain	0.9900

AlphaMissense

1963 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:10989721:G:C	F249L	1.000
6:10989721:G:T	F249L	1.000
6:10989723:A:G	F249L	1.000
6:10989829:G:C	F213L	0.999
6:10989829:G:T	F213L	0.999
6:10989831:A:G	F213L	0.999
6:10990347:A:G	W201R	0.999
6:10990347:A:T	W201R	0.999
6:10990410:G:C	H180D	0.999
6:10995062:A:C	H150Q	0.999
6:10995062:A:T	H150Q	0.999
6:10995064:G:C	H150D	0.999
6:10995067:G:C	H149D	0.999
6:10995143:T:A	K123N	0.999
6:10995143:T:G	K123N	0.999
6:10995144:T:A	K123I	0.999
6:10989712:A:C	F252L	0.998
6:10989712:A:T	F252L	0.998
6:10989714:A:G	F252L	0.998
6:10990321:C:A	Q209H	0.998
6:10990321:C:G	Q209H	0.998
6:10990342:C:A	K202N	0.998
6:10990342:C:G	K202N	0.998
6:10990408:G:C	H180Q	0.998
6:10990408:G:T	H180Q	0.998
6:10990417:A:C	S177R	0.998
6:10990417:A:T	S177R	0.998
6:10990419:T:G	S177R	0.998
6:10990420:G:C	N176K	0.998
6:10990420:G:T	N176K	0.998

dbSNP variants (sampled 300 via entrez): RS1000078669 (6:11043841 G>A,C), RS1000139835 (6:10998117 T>C,G), RS1000182254 (6:11017584 C>T), RS1000210665 (6:10999653 C>T), RS1000251122 (6:11024912 G>A), RS1000255644 (6:11017298 G>A,C), RS1000279654 (6:10997894 A>C), RS1000284715 (6:11017595 C>T), RS1000346351 (6:11011079 G>T), RS1000431482 (6:11025499 C>A,G), RS1000510293 (6:11015684 A>G,T), RS1000536485 (6:10982267 A>C), RS1000583461 (6:11015413 A>G), RS1000621674 (6:11019659 A>T), RS1000726237 (6:11005935 C>A)

Disease associations

OMIM: gene MIM:611814 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001177_1	Plasma omega-3 polyunsaturated fatty acid levels (docosahexaenoic acid)	1.000000e-15
GCST001178_2	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	2.000000e-12
GCST001179_4	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	1.000000e-43
GCST001217_8	Metabolic traits	2.000000e-14
GCST001414_5	Phospholipid levels (plasma)	1.000000e-11
GCST001639_22	Metabolite levels	4.000000e-09
GCST002448_1	Plasma omega-6 polyunsaturated fatty acid levels (adrenic acid)	7.000000e-07
GCST002712_5	Red blood cell fatty acid levels	4.000000e-09
GCST003830_12	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	8.000000e-07
GCST003830_29	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	5.000000e-07
GCST003830_44	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	8.000000e-07
GCST005650_17	Serum metabolite ratios in chronic kidney disease	2.000000e-13
GCST009028_3	Adverse response to drug	5.000000e-07
GCST009172_2	Response to (pegylated) interferon in HBeAg-negative hepatitis B	3.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007761	docosahexaenoic acid measurement
EFO:0007760	eicosapentaenoic acid measurement
EFO:0006809	docosapentaenoic acid measurement
EFO:0004725	metabolite measurement
EFO:0004723	coronary artery calcification
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0005921	FEV change measurement
EFO:0009658	adverse effect
EFO:0007859	response to interferon

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5911 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	6
Estradiol	affects cotreatment, decreases expression, increases expression	4
bisphenol A	affects expression, affects cotreatment, increases methylation, decreases expression	3
trichostatin A	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Cyclosporine	decreases expression	3
potassium chromate(VI)	decreases expression, increases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
arsenite	increases methylation	1
methylparaben	decreases expression	1
afimoxifene	decreases reaction, increases expression	1
perfluorooctanoic acid	increases expression	1
periodate-oxidized adenosine	affects expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
obeticholic acid	increases expression	1
ICG 001	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007919	Binding	Inhibition of human ELOVL2 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery