AREL1

Summary

AREL1 (apoptosis resistant E3 ubiquitin protein ligase 1, HGNC:20363) is a protein-coding gene on chromosome 14q24.3, encoding Apoptosis-resistant E3 ubiquitin protein ligase 1 (O15033). E3 ubiquitin-protein ligase that catalyzes ‘Lys-11’- or ‘Lys-33’-linked polyubiquitin chains, with some preference for ‘Lys-33’ linkages.

Enables ubiquitin protein ligase activity. Involved in negative regulation of apoptotic process; protein polyubiquitination; and ubiquitin-dependent protein catabolic process. Located in cytosol.

Source: NCBI Gene 9870 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 143 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001039479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20363
Approved symbol	AREL1
Name	apoptosis resistant E3 ubiquitin protein ligase 1
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FIEL1
Ensembl gene	ENSG00000119682
Ensembl biotype	protein_coding
OMIM	615380
Entrez	9870

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 13 protein_coding, 5 nonsense_mediated_decay, 4 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000356357, ENST00000469797, ENST00000481010, ENST00000553279, ENST00000554070, ENST00000554525, ENST00000555249, ENST00000555330, ENST00000556202, ENST00000556327, ENST00000556589, ENST00000556860, ENST00000557401, ENST00000557688, ENST00000680030, ENST00000681099, ENST00000681535, ENST00000681599, ENST00000880345, ENST00000880346, ENST00000880347, ENST00000880348, ENST00000919344, ENST00000919345, ENST00000919346, ENST00000951857

RefSeq mRNA: 2 — MANE Select: NM_001039479 NM_001039479, NM_001411046

CCDS: CCDS41971, CCDS91905

Canonical transcript exons

ENST00000356357 — 20 exons

Exon	Start	End
ENSE00001400828	74661256	74663822
ENSE00001605395	74692041	74692328
ENSE00002479769	74712933	74713080
ENSE00003469963	74669947	74670126
ENSE00003472605	74685600	74685660
ENSE00003481000	74667319	74667377
ENSE00003485692	74670762	74670871
ENSE00003542117	74672831	74672952
ENSE00003556538	74663899	74664074
ENSE00003578500	74669649	74669774
ENSE00003597725	74676583	74676752
ENSE00003616587	74671408	74671483
ENSE00003624442	74667465	74667594
ENSE00003626781	74675699	74675946
ENSE00003634154	74674034	74674111
ENSE00003640611	74673077	74673218
ENSE00003658133	74664836	74664925
ENSE00003664484	74676141	74676321
ENSE00003665463	74683296	74683533
ENSE00003669612	74684454	74684680

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 92.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.9326 / max 255.3322, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144086	15.9326	1813

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.13	gold quality
cortical plate	UBERON:0005343	91.15	gold quality
blood	UBERON:0000178	89.84	gold quality
adrenal tissue	UBERON:0018303	89.76	gold quality
stromal cell of endometrium	CL:0002255	89.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.74	gold quality
leukocyte	CL:0000738	88.16	gold quality
monocyte	CL:0000576	88.13	gold quality
granulocyte	CL:0000094	88.07	gold quality
mononuclear cell	CL:0000842	87.96	gold quality
bone marrow cell	CL:0002092	87.96	gold quality
rectum	UBERON:0001052	87.39	gold quality
right lobe of thyroid gland	UBERON:0001119	87.06	gold quality
bone marrow	UBERON:0002371	87.03	gold quality
ileal mucosa	UBERON:0000331	87.02	gold quality
left lobe of thyroid gland	UBERON:0001120	86.72	gold quality
prefrontal cortex	UBERON:0000451	86.60	gold quality
islet of Langerhans	UBERON:0000006	86.49	gold quality
ganglionic eminence	UBERON:0004023	86.31	gold quality
ventricular zone	UBERON:0003053	86.24	gold quality
thyroid gland	UBERON:0002046	85.92	gold quality
lower esophagus mucosa	UBERON:0035834	85.56	gold quality
metanephros cortex	UBERON:0010533	85.51	gold quality
right adrenal gland cortex	UBERON:0035827	85.33	gold quality
gastrocnemius	UBERON:0001388	84.80	gold quality
right frontal lobe	UBERON:0002810	84.76	gold quality
muscle of leg	UBERON:0001383	84.74	gold quality
left adrenal gland cortex	UBERON:0035825	84.68	gold quality
upper lobe of left lung	UBERON:0008952	84.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.66	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.23

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFbeta signaling pathway through the site-specific ubiquitination of PIAS4. (PMID:27162139)
• The AREL1 HECT domain assembled Lys(33)-, Lys(48)-, and Lys(63)-linked polyubiquitin chains. E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination. (PMID:31732561)
• Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients. (PMID:32151281)
• AREL1 resists the apoptosis induced by TGF-beta by inhibiting SMAC in vascular endothelial cells. (PMID:37522329)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	AREL1	ENSDARG00000100359
mus_musculus	Arel1	ENSMUSG00000042350
rattus_norvegicus	Arel1	ENSRNOG00000004382
drosophila_melanogaster	CG4238	FBGN0031384

Paralogs (24): HECW1 (ENSG00000002746), UBE3C (ENSG00000009335), NEDD4L (ENSG00000049759), NEDD4 (ENSG00000069869), ITCH (ENSG00000078747), HACE1 (ENSG00000085382), HUWE1 (ENSG00000086758), HECTD1 (ENSG00000092148), UBR5 (ENSG00000104517), SMURF2 (ENSG00000108854), UBE3A (ENSG00000114062), WWP1 (ENSG00000123124), HERC2 (ENSG00000128731), HECW2 (ENSG00000138411), HERC3 (ENSG00000138641), HERC6 (ENSG00000138642), HERC5 (ENSG00000138646), HERC4 (ENSG00000148634), UBE3B (ENSG00000151148), TRIP12 (ENSG00000153827), HECTD2 (ENSG00000165338), HECTD4 (ENSG00000173064), WWP2 (ENSG00000198373), SMURF1 (ENSG00000198742)

Protein

Protein identifiers

Apoptosis-resistant E3 ubiquitin protein ligase 1 — O15033 (reviewed: O15033)

Alternative names: Apoptosis-resistant HECT-type E3 ubiquitin transferase 1

All UniProt accessions (9): O15033, A0A7P0T811, A0A7P0Z4H7, G3V245, G3V2B5, G3V506, G3V5P7, H0YJ67, H0YJ69

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that catalyzes ‘Lys-11’- or ‘Lys-33’-linked polyubiquitin chains, with some preference for ‘Lys-33’ linkages. E3 ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Ubiquitinates SEPTIN4, DIABLO/SMAC and HTRA2 in vitro. Modulates pulmonary inflammation by targeting SOCS2 for ubiquitination and subsequent degradation by the proteasome.

Subunit / interactions. Interacts with SOCS2. Interacts (via HECT domain) with HTRA2, DIABLO/SMAC and SEPTIN4; in the cytoplasm following induction of apoptosis.

Post-translational modifications. Autoubiquitinated in vitro in the presence of E2 enzyme UBE2D1/UBCH5A.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
O15033-1	1	yes
O15033-2	2

RefSeq proteins (2): NP_001034568, NP_001397975 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000569	HECT_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR017868	Filamin/ABP280_rpt-like	Repeat
IPR035983	Hect_E3_ubiquitin_ligase	Homologous_superfamily
IPR050409	E3_ubiq-protein_ligase	Family
IPR058738	PH-like_AREL1	Domain
IPR058906	AREL1_N	Domain

Pfam: PF00630, PF00632, PF25915, PF25916

Enzyme classification (BRENDA):

• EC 2.3.2.26 — HECT-type E3 ubiquitin transferase (BRENDA: 14 organisms, 64 substrates, 19 inhibitors, 5 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBC5B]-L-LYSINE	0.0046–0.037	5

UniProt features (51 total): helix 22, strand 14, turn 4, sequence conflict 2, region of interest 2, chain 1, repeat 1, domain 1, active site 1, splice variant 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6JX5	X-RAY DIFFRACTION	2.4
6LOH	X-RAY DIFFRACTION	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15033-F1	84.00	0.49

Functional residue map

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

Catalytic / active sites (1): 790 (glycyl thioester intermediate)

Mutagenesis-validated functional residues (1):

Position	Phenotype
790	failure to form ubiquitin thioester complex.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 158 (showing top): ELVIDGE_HYPOXIA_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, chr14q24, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_PROTEIN_K11_LINKED_UBIQUITINATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (7): ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), protein ubiquitination (GO:0016567), negative regulation of apoptotic process (GO:0043066), regulation of inflammatory response (GO:0050727), protein K11-linked ubiquitination (GO:0070979), protein K33-linked ubiquitination (GO:1990390)

GO Molecular Function (4): ubiquitin-protein transferase activity (GO:0004842), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein polyubiquitination	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
protein modification by small protein conjugation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
ubiquitin-like protein transferase activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AREL1	VRTN	Q9H8Y1	622
AREL1	PROX2	Q3B8N5	598
AREL1	YLPM1	P49750	548
AREL1	LRRC74A	Q0VAA2	505
AREL1	FAM161B	Q96MY7	478
AREL1	SYNDIG1L	A6NDD5	475
AREL1	RPS6KL1	Q9Y6S9	474
AREL1	MTX3	Q5HYI7	472
AREL1	FCF1	Q9Y324	471
AREL1	TRIM41	Q8WV44	465
AREL1	TRIM36	Q9NQ86	462
AREL1	UBE2C	O00762	443
AREL1	MTX2	O75431	436
AREL1	HEATR4	Q86WZ0	429
AREL1	NCBP2	P52298	420

IntAct

22 interactions, top by confidence:

A	B	Type	Score
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CRKL	AREL1	psi-mi:“MI:0915”(physical association)	0.490
AREL1	CRKL	psi-mi:“MI:0915”(physical association)	0.490
AREL1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
PCDHGB4	FAM171A2	psi-mi:“MI:0914”(association)	0.350
PCDHGC4		psi-mi:“MI:0914”(association)	0.350
ATP2A3	GPR89A	psi-mi:“MI:0914”(association)	0.350
EVA1B	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PCDHGB2	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	AREL1	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC4A9	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC9A3	ESYT3	psi-mi:“MI:0914”(association)	0.350
SLC9A5	NBAS	psi-mi:“MI:0914”(association)	0.350
	AREL1	psi-mi:“MI:0915”(physical association)	0.000
AREL1	hisH	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (167): AREL1 (Two-hybrid), UBC (Biochemical Activity), UBE2L3 (Reconstituted Complex), UBC (Biochemical Activity), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D3 (Reconstituted Complex), UBE2L3 (Reconstituted Complex), AREL1 (Biochemical Activity), UBE2D1 (Reconstituted Complex), AREL1 (Affinity Capture-Western), PIAS4 (Biochemical Activity), PIAS4 (Affinity Capture-Western), AREL1 (Protein-peptide), GSK3B (Affinity Capture-Western)

ESM2 similar proteins: A0A3Q1LSX9, A2A5R2, A2APV2, A4IID4, A9X1A0, B0KWC1, B1MTG7, B2KI64, B3EX61, B4UT09, D3ZBM7, D4A631, E1C656, F1N6G5, F8W2M1, G3X9K3, G5EBH0, O02810, O08561, O08759, O15033, O46382, P42285, Q05086, Q15386, Q16UN6, Q21029, Q28BK1, Q3U0D9, Q49GP3, Q5GLZ8, Q5PQN1, Q5RD78, Q5U5R9, Q6DCL5, Q6GN16, Q6IN85, Q6NXC0, Q6P2K6, Q6PAV2

Diamond homologs: A0A8C0NGY6, A1CQG2, A1D3C5, A2A5Z6, A2QQ28, A9JRZ0, B0XQ72, B8N7E5, D3ZBM7, D6C652, E1B7Q7, E1C656, F1LP64, F1N6G5, F8W2M1, G0S9J5, G5E870, H2LBU8, O00308, O08759, O13834, O14326, O15033, P39940, P40985, P46934, P46935, P46937, P46938, P51593, P53119, Q03280, Q05086, Q08CZ0, Q09291, Q0CCL1, Q14669, Q15034, Q15386, Q1K9C4

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
AREL1	“down-regulates quantity by destabilization”	DIABLO	ubiquitination
AREL1	“down-regulates quantity by destabilization”	HTRA2	ubiquitination
AREL1	“down-regulates quantity by destabilization”	SEPTIN4	ubiquitination
AREL1	“down-regulates quantity by destabilization”	MTX2	ubiquitination
Ub:E2	“up-regulates activity”	AREL1	ubiquitination
GSK3B	“down-regulates quantity by destabilization”	AREL1	phosphorylation
AREL1	“down-regulates quantity by destabilization”	PIAS4	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
SLC-mediated transmembrane transport	5	19.7×	2e-04
Transport of small molecules	6	10.1×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	115
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3523 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74663823:C:CC	acceptor_gain	1.0000
14:74664831:TTTA:T	donor_loss	1.0000
14:74664832:TTA:T	donor_loss	1.0000
14:74664833:TA:T	donor_loss	1.0000
14:74664834:A:C	donor_loss	1.0000
14:74664921:AGCAG:A	acceptor_gain	1.0000
14:74664922:GCAG:G	acceptor_gain	1.0000
14:74664923:CAG:C	acceptor_gain	1.0000
14:74664923:CAGC:C	acceptor_gain	1.0000
14:74664924:AG:A	acceptor_gain	1.0000
14:74664924:AGC:A	acceptor_loss	1.0000
14:74664925:GC:G	acceptor_loss	1.0000
14:74664926:C:CC	acceptor_gain	1.0000
14:74664926:C:T	acceptor_loss	1.0000
14:74664927:T:C	acceptor_loss	1.0000
14:74666525:T:C	donor_gain	1.0000
14:74667313:ACTT:A	donor_loss	1.0000
14:74667314:CTTA:C	donor_loss	1.0000
14:74667315:TTACC:T	donor_loss	1.0000
14:74667316:TA:T	donor_loss	1.0000
14:74667317:A:AC	donor_gain	1.0000
14:74667318:C:CA	donor_loss	1.0000
14:74667318:C:CC	donor_gain	1.0000
14:74667318:CCT:C	donor_gain	1.0000
14:74667373:CAGGC:C	acceptor_gain	1.0000
14:74667375:GGC:G	acceptor_gain	1.0000
14:74667376:GCC:G	acceptor_loss	1.0000
14:74667378:C:CC	acceptor_gain	1.0000
14:74667378:C:G	acceptor_loss	1.0000
14:74667379:T:G	acceptor_loss	1.0000

AlphaMissense

5410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74663732:A:C	F820L	1.000
14:74663732:A:T	F820L	1.000
14:74663734:A:G	F820L	1.000
14:74663811:A:G	L794P	1.000
14:74663914:G:C	P785R	1.000
14:74663914:G:T	P785H	1.000
14:74663915:G:A	P785S	1.000
14:74663915:G:T	P785T	1.000
14:74664006:G:C	F754L	1.000
14:74664006:G:T	F754L	1.000
14:74664007:A:G	F754S	1.000
14:74664008:A:G	F754L	1.000
14:74664016:A:G	L751P	1.000
14:74667323:A:G	L700P	1.000
14:74667337:A:C	F695L	1.000
14:74667337:A:T	F695L	1.000
14:74667339:A:G	F695L	1.000
14:74667374:A:G	L683P	1.000
14:74667465:C:G	G682R	1.000
14:74667518:G:T	A664D	1.000
14:74667521:A:G	L663P	1.000
14:74667534:A:C	Y659D	1.000
14:74667557:A:T	V651D	1.000
14:74670056:C:T	G560D	1.000
14:74670068:C:T	G556E	1.000
14:74670069:C:G	G556R	1.000
14:74670069:C:T	G556R	1.000
14:74670842:A:G	W510R	1.000
14:74670842:A:T	W510R	1.000
14:74671447:A:G	W487R	1.000

dbSNP variants (sampled 300 via entrez): RS1000065189 (14:74677724 A>G), RS1000124777 (14:74712467 A>G), RS1000147040 (14:74684280 A>C), RS1000153733 (14:74686758 G>A), RS1000237749 (14:74673543 A>G), RS1000380652 (14:74680453 G>A), RS1000390134 (14:74680531 C>T), RS1000459722 (14:74704699 C>A,T), RS1000490526 (14:74685362 G>T), RS1000502392 (14:74666430 T>C,G), RS1000504705 (14:74672154 T>C), RS1000554594 (14:74664900 A>T), RS1000665955 (14:74679240 T>C), RS1000678054 (14:74678951 C>T), RS1000886913 (14:74680218 G>A)

Disease associations

OMIM: gene MIM:615380 | disease phenotypes: MIM:114500, MIM:614385

GenCC curated gene-disease

Mondo (3): endometrial carcinoma (MONDO:0002447), colorectal cancer (MONDO:0005575), colorectal cancer, hereditary nonpolyposis, type 7 (MONDO:0013725)

Orphanet (2): Lynch syndrome (Orphanet:144), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0012114	Endometrial carcinoma

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005237_3	Mood instability	1.000000e-06
GCST005238_3	Mood instability	3.000000e-09
GCST007709_129	General factor of neuroticism	2.000000e-10
GCST007709_131	General factor of neuroticism	6.000000e-09
GCST90011770_68	Glaucoma (primary open-angle)	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008475	mood instability measurement
EFO:0007660	neuroticism measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565777	Colorectal Cancer, Hereditary Nonpolyposis, Type 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Ozone	increases abundance, affects cotreatment, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation	1
hydroxyhydroquinone	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
pinostrobin	increases expression	1
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression, affects cotreatment, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Folic Acid	decreases expression	1
Smoke	decreases expression	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00719017	PHASE4	UNKNOWN	Upper Vaginectomy Versus Brachytherapy in Patients With Early Stage Endometrial Cancer Treated With Laparoscopic Surgery
NCT02543710	PHASE4	RECRUITING	Biomarker Guided Treatment in Gynaecological Cancer
NCT03349463	PHASE4	UNKNOWN	Evaluation of Fluciclovine Uptake in Patients With Cervical, Ovarian Epithelial or Endometrial Cancers.
NCT03752606	PHASE4	COMPLETED	Application of Tachosil During Lymphadenectomy
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT06049693	PHASE4	COMPLETED	Iron Prehabilitation in Endometrial Cancer
NCT06726291	PHASE4	RECRUITING	Akynzeo as Antiemetic Treatment in Patients With Endometrial Cancer
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT07281547	PHASE4	NOT_YET_RECRUITING	Low Dose Aspirin to Lower Inflammation and Prevent Endometrial Cancer in Postmenopausal Women With Non-atrophic Endometrial Changes and Pain
NCT07462663	PHASE4	NOT_YET_RECRUITING	SHAPE-ENDO: Multimodal Pre-Surgical Optimization in Patients With Obesity and Early-Stage Endometrial Cancer (Phase 1)
NCT00002459	PHASE3	COMPLETED	Radiation Therapy or No Further Treatment Following Surgery in Treating Patients With Cancer of the Uterus
NCT00002493	PHASE3	COMPLETED	Radiation Therapy Compared With Combination Chemotherapy in Treating Patients With Advanced Endometrial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002920	PHASE3	COMPLETED	S9630, Medroxyprogesterone in Treating Women With Breast Cancer
NCT00002976	PHASE3	TERMINATED	Estrogen Replacement Therapy in Treating Women With Early-Stage Endometrial Cancer
NCT00003267	PHASE3	COMPLETED	Pelvic Drains After Radical Hysterectomy in Treating Patients With Uterine, Cervical, or Vaginal Cancer
NCT00003691	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer
NCT00003749	PHASE3	COMPLETED	Surgery With or Without Lymphadenectomy and Radiation Therapy in Treating Patients With Endometrial Cancer
NCT00005583	PHASE3	COMPLETED	Radiation Therapy With or Without Chemotherapy in Treating Patients With High-Risk Endometrial Cancer
NCT00006027	PHASE3	COMPLETED	Comparison of Radiation Therapy With or Without Combination Chemotherapy Following Surgery in Treating Patients With Stage I or Stage II Endometrial Cancer
NCT00016341	PHASE3	TERMINATED	Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer
NCT00033605	PHASE3	COMPLETED	Octreotide in Preventing Diarrhea in Patients Who Are Undergoing Radiation Therapy to the Pelvis
NCT00096408	PHASE3	COMPLETED	Laparoscopic Approach to Cancer of the Endometrium
NCT00245050	PHASE3	COMPLETED	Pyridoxine in Preventing Hand-Foot Syndrome in Patients Who Are Receiving Liposomal Doxorubicin for Cancer
NCT00376844	PHASE3	COMPLETED	External-Beam Radiation Therapy Compared With Vaginal Brachytherapy After Surgery for Stage I Endometrial Cancer
NCT00411138	PHASE3	UNKNOWN	Randomized Trial of Radiation Therapy With or Without Chemotherapy for Endometrial Cancer
NCT00566644	PHASE3	TERMINATED	Intrauterine Levonorgestrel and Observation or Observation Alone in Preventing Atypical Endometrial Hyperplasia and Endometrial Cancer in Women With Hereditary Non-Polyposis Colorectal Cancer or Lynch Syndrome
NCT00883116	PHASE3	TERMINATED	A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer
NCT01087268	PHASE3	UNKNOWN	Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer
NCT01470677	PHASE3	COMPLETED	Tachosil for the Prevention of Symptomatic Lymph Cysts
NCT01672892	PHASE3	COMPLETED	Standard Versus Intensity-Modulated Pelvic Radiation Therapy in Treating Patients With Endometrial or Cervical Cancer
NCT01767155	PHASE3	COMPLETED	Zoptarelin Doxorubicin (AEZS 108) as Second Line Therapy for Endometrial Cancer
NCT02584478	PHASE3	UNKNOWN	Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002)
NCT02762214	PHASE3	UNKNOWN	Role of Uterine Manipulator in Hysterectomy - Ro.Man.HY
NCT03469674	PHASE3	ACTIVE_NOT_RECRUITING	PORTEC-4a: Molecular Profile-based Versus Standard Adjuvant Radiotherapy in Endometrial Cancer
NCT03555422	PHASE3	COMPLETED	Maintenance With Selinexor/Placebo After Combination Chemotherapy in Participants With Endometrial Cancer [SIENDO]
NCT03603184	PHASE3	COMPLETED	Atezolizumab Trial in Endometrial Cancer - AtTEnd
NCT03785288	PHASE3	RECRUITING	Vaginal Cuff Brachytherapy Fractionation Study