MECOM

Summary

MECOM (MDS1 and EVI1 complex locus, HGNC:3498) is a protein-coding gene on chromosome 3q26.2, encoding Histone-lysine N-methyltransferase MECOM (Q03112). Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression.

The protein encoded by this gene is a transcriptional regulator and oncoprotein that may be involved in hematopoiesis, apoptosis, development, and cell differentiation and proliferation. The encoded protein can interact with CTBP1, SMAD3, CREBBP, KAT2B, MAPK8, and MAPK9. This gene can undergo translocation with the AML1 gene, resulting in overexpression of this gene and the onset of leukemia. Several transcript variants encoding a few different isoforms have been found for this gene.

Source: NCBI Gene 2122 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MECOM-associated syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 112
• Clinical variants (ClinVar): 1,747 total — 19 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_004991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3498
Approved symbol	MECOM
Name	MDS1 and EVI1 complex locus
Location	3q26.2
Locus type	gene with protein product
Status	Approved
Aliases	MDS1-EVI1, PRDM3, KMT8E
Ensembl gene	ENSG00000085276
Ensembl biotype	protein_coding
OMIM	165215
Entrez	2122

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264674, ENST00000433243, ENST00000460814, ENST00000460890, ENST00000461430, ENST00000464456, ENST00000466623, ENST00000468789, ENST00000472280, ENST00000475754, ENST00000481315, ENST00000484519, ENST00000485957, ENST00000486748, ENST00000487503, ENST00000492586, ENST00000494292, ENST00000494597, ENST00000628990, ENST00000651503

RefSeq mRNA: 16 — MANE Select: NM_004991 NM_001105077, NM_001105078, NM_001163999, NM_001164000, NM_001205194, NM_001366466, NM_001366467, NM_001366468, NM_001366469, NM_001366470, NM_001366471, NM_001366472, NM_001366473, NM_001366474, NM_004991, NM_005241

CCDS: CCDS3205, CCDS54669, CCDS54670, CCDS93423, CCDS93424, CCDS93425

Canonical transcript exons

ENST00000651503 — 17 exons

Exon	Start	End
ENSE00001934229	169083507	169085043
ENSE00002023899	169115383	169116739
ENSE00002047842	169092958	169093102
ENSE00002048259	169102060	169102226
ENSE00002051786	169089000	169089183
ENSE00002053801	169095076	169095245
ENSE00002061956	169100885	169100962
ENSE00002064224	169090000	169090236
ENSE00002067672	169112787	169112874
ENSE00002073440	169121056	169121209
ENSE00002073683	169127844	169128060
ENSE00002077167	169107926	169107952
ENSE00002085537	169122580	169122727
ENSE00003587778	169131429	169131531
ENSE00003648844	169143698	169143832
ENSE00003669216	169381187	169381524
ENSE00003889198	169663336	169663712

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 98.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0935 / max 320.2203, expressed in 1082 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45523	2.5728	597
45494	1.2410	577
45500	0.6458	363
45522	0.4038	199
45501	0.2455	103
45495	0.1792	96
45499	0.1646	57
45498	0.1366	49
45497	0.1111	40
45524	0.1032	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	98.91	gold quality
renal medulla	UBERON:0000362	98.90	gold quality
pylorus	UBERON:0001166	98.82	gold quality
nasal cavity epithelium	UBERON:0005384	96.84	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.77	gold quality
bronchial epithelial cell	CL:0002328	96.58	gold quality
visceral pleura	UBERON:0002401	96.52	gold quality
epithelium of bronchus	UBERON:0002031	96.13	gold quality
bronchus	UBERON:0002185	96.04	gold quality
mucosa of urinary bladder	UBERON:0001259	95.21	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.58	gold quality
lower lobe of lung	UBERON:0008949	94.47	gold quality
stomach	UBERON:0000945	94.42	gold quality
epithelium of nasopharynx	UBERON:0001951	94.26	gold quality
nasopharynx	UBERON:0001728	94.24	gold quality
esophagus squamous epithelium	UBERON:0006920	94.22	gold quality
colonic mucosa	UBERON:0000317	94.01	gold quality
body of stomach	UBERON:0001161	93.97	gold quality
buccal mucosa cell	CL:0002336	93.38	gold quality
nasal cavity mucosa	UBERON:0001826	92.63	gold quality
fundus of stomach	UBERON:0001160	92.57	gold quality
urethra	UBERON:0000057	92.23	gold quality
endometrium	UBERON:0001295	91.97	gold quality
rectum	UBERON:0001052	91.90	gold quality
kidney	UBERON:0002113	91.80	gold quality
adult mammalian kidney	UBERON:0000082	91.54	gold quality
pericardium	UBERON:0002407	91.52	gold quality
metanephros cortex	UBERON:0010533	91.40	gold quality
epithelium of esophagus	UBERON:0001976	91.15	gold quality
calcaneal tendon	UBERON:0003701	91.14	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	12743.31
E-CURD-119	yes	12029.65
E-MTAB-11268	yes	7516.96
E-ANND-2	yes	5147.00
E-HCAD-10	yes	54.45
E-MTAB-10287	yes	51.28
E-GEOD-135922	yes	41.88
E-HCAD-35	yes	27.64
E-ANND-3	yes	22.43
E-MTAB-5061	yes	20.39
E-ENAD-27	yes	6.30
E-MTAB-9801	yes	4.87
E-CURD-135	no	851.54
E-GEOD-75140	no	203.11
E-MTAB-8271	no	168.89

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
ANGPT1	Activation
ANGPT2	Activation
CA3	Repression
CALCA
CALR
CLDN1
CSF1R
E2F1	Unknown
FOS	Activation
GATA1	Activation
GATA2	Activation
MAP2	Activation
MBD3
MECOM
PBX1	Activation
PPARG	Activation
SERPINE1	Repression
SMAD7	Repression
TEK	Activation
ZBTB16	Activation

Upstream regulators (CollecTRI, top): ELK1, GATA6, LMO2, MECOM, MEF2C, NKX2-5, RUNX1, SMARCA4, SOX4, SOX9

miRNA regulators (miRDB)

83 targeting MECOM, 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-6873-3P	100.00	71.42	2626
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-182-5P	99.87	74.03	2589

Literature-anchored findings (GeneRIF, showing 40)

• Data indicate that EVI1 is involved in megakaryocytic differentiation, and the dysmegakaryocytopoiesis in 3q21q26 syndrome could be partly due to an enhanced differentiation of leukemia cells and/or megakaryocytes by constitutive expression of EVI1. (PMID:11922610)
• study investigated which of the 2 gene products, AMLEVI1 or MDS1-EVI1, is involved in acute myeloid leukemia transformation and found that AMLEVI1 and not MDS1-EVI1 expression was associated with unfavorable karyotypes (PMID:12393383)
• EVI1 promotes cell proliferation by interacting with BRG1 and blocking the repression of BRG1 on E2F1 activity (PMID:14555651)
• Evi-1 acts as a general Smad corepressor to inhibit TGF-beta-, activin-, and BMP-inducible transcription (PMID:15849193)
• results suggest that oligomerization may contribute to the oncogenic potential of Evi-1-containing proteins (PMID:15897867)
• human AML1/EVI1/+ knock-in mouse embryos showed defective hematopoiesis in the fetal liver; fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte (PMID:15914564)
• The general expression patterns of the EVI1 5’-end variants in a panel of 20 human tissues were similar, while pronounced differences were noted in response to all-trans retinoic acid. (PMID:16014322)
• Real-time quantitative PCR analyses indicated that typically both MDS1/EVI1 and EVI1, but not MDS1, were expressed in these malignancies, with EVI1 the primary transcript. (PMID:16342172)
• Correction of X-linked chronic granulomatous disease by gene therapy was augmented by insertional activation of MDS1. (PMID:16582916)
• Murine and human forms of Evi1 with repressor domain(Rp) or Rp+9 exist, the additional 9 amino acids are encoded by a conserved 27 nucleotide exon, the overall structural organisation of the gene being preserved in the two species. (PMID:17014970)
• Overexpressed in Fanconi anemia-derived acute myeloid leukemia. (PMID:17243162)
• review of EVI1 expression, biochemical properties, and biological functions [review] (PMID:17507183)
• ubiquitously-expressed transcript suppresses cell transformation and might mediate this function by interaction and inhibition of the biological activity of cell proliferation and survival stimulatory factors like Evi1 (PMID:17635584)
• High EVI1 expression is associated with acute myeloid leukemias (PMID:17693189)
• In conclusion, the combined MDS-EVI1/EVI1 gene may serve as an alternative MRD marker in AML, especially in samples where other specific markers are lacking. (PMID:17693194)
• Inhibition of C/EBPalpha function may be causatively related to the leukemogenic potential of RUNX1/EVI1 chimeric transcription factor. (PMID:17894555)
• EVI1 and MDS1/EVI1 overexpression is associated with acute myeloid leukemia (PMID:18181178)
• Genetic alterations such as aberrant expression of the EVI1 gene may contribute to the clinical heterogeneity of chronic myeloid leukemia. (PMID:18262061)
• High EVI1 predicted a distinctly worse event-free survival (HR = 1.9; P = .002) and disease-free survival (HR = 2.1, P = .006) following multivariate analysis. (PMID:18272813)
• Evi-1 promotes hematopoietic stem/progenitor expansion at the embryonic stage through up-regulation of GATA-2 and repression of TGF-beta signaling. (PMID:18452556)
• Presence of SUV39H1 enhances Evi1 transcriptional repression in a dose dependent manner; these data establish an epigenetic role of Evi1 in cell transformation by recruiting higher order chromatin remodeling complexes. (PMID:18619962)
• Presence of both EVI1 and/or BAALC in chronic myeloid patients was found to modulate the disease pattern (PMID:18752846)
• The EVI1 gene locus was rearranged in all 13 myeloid malignancies patients and was associated with EVI1 overexpression. In 9 out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band 17q22 encompassing the MSI2 gene (PMID:18815193)
• ETV6/RUNX1 leads to EPOR up-regulation and that activation by EPO might be of relevance to the biology of ETV6/RUNX1-positive acute lymphoblastic leukemias (PMID:19010836)
• EVI1 point mutant, unable to bind PU.1, restores the activation of PU.1-regulated genes and allows a normal differentiation of bone marrow progenitors in vitro. (PMID:19208846)
• both NUP98/HOXA9 and NUP98/HOXA11 enhance the activity of the EVI1 promoter (PMID:19241117)
• It is a critical regulator for hematopoiesis and leukemia. (review) (PMID:19352083)
• biochemical properties and biological functions of EVI-1 in normal and malignant hematopoiesis, with specific focus on its pathogenetic significance in hematological malignancies. (PMID:19385966)
• inducible expression of EVI1 in U937 cells causes phenotypes that may be relevant for its role in MDS and provides a basis for further investigation of its contribution to this fatal disease. (PMID:19605700)
• Pbx1 is a target gene of Evi-1 involved in Evi-1-mediated leukemogenesis. (PMID:19767769)
• EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization. (PMID:19776757)
• performed high-resolution array comparative genomic hybridization analysis of twelve EVI1 overexpressing patients and three EVI1 deregulated cell lines to search for 7q submicroscopic deletions (PMID:20084277)
• data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia (PMID:20098431)
• EVI1 expression in acute myeloid leukemia(AML) is unequally distributed in cytogenetic subtypes. It predicts poor outcome, particularly among intermediate cytogenetic risk AML. (PMID:20308656)
• EVI1 is overexpressed in specific cytogenetic (MLL rearrangements and monosomy 7) and morphologic (FAB-M6/7) subtypes of pediatric acute myeloid leukemia. (PMID:20357826)
• acetylation of EVI1 at Lys(564) by P/CAF enhances the DNA binding capacity of EVI1 and thereby contributes to the activation of GATA2 (PMID:20363750)
• Findings provide new insights into the pathogenesis of NPC by highlighting the involvement of pathways related to TNFRSF19 and MDS1-EVI1 in addition to HLA molecules. (PMID:20512145)
• Proteins associated with EVI1, signaling pathways regulated by EVI1, and downstream mediators of EVI1 transcriptional regulation have been described and characterized. (PMID:20532840)
• EVI1 controls proliferation in acute myeloid leukemia through modulation of miR-1-2. (PMID:20842122)
• Aberrant DNA hypermethylation signature is associated with acute myeloid leukemia directed by EVI1. (PMID:20855866)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mecom	ENSDARG00000060808
mus_musculus	Mecom	ENSMUSG00000027684
rattus_norvegicus	Mecom	ENSRNOG00000012645
drosophila_melanogaster	CG10348	FBGN0032707
drosophila_melanogaster	ham	FBGN0045852
caenorhabditis_elegans		WBGENE00001207

Paralogs (1): PRDM16 (ENSG00000142611)

Protein

Protein identifiers

Histone-lysine N-methyltransferase MECOM — Q03112 (reviewed: Q03112)

Alternative names: Ecotropic virus integration site 1 protein homolog, MDS1 and EVI1 complex locus protein, Myelodysplasia syndrome 1 protein, Myelodysplasia syndrome-associated protein 1

All UniProt accessions (10): Q03112, A0A0C3SFZ7, A0A1B0GXI8, C9JU02, E7EPY2, E7ERX0, E7EU48, E7EUL6, E9PGE9, H9KVD4

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis. Displays histone methyltransferase activity and monomethylates ‘Lys-9’ of histone H3 (H3K9me1). Probably catalyzes the monomethylation of free histone H3 in the cytoplasm which is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases use it as a substrate to catalyze histone H3 ‘Lys-9’ trimethylation. Likely to be one of the primary histone methyltransferases along with PRDM16 that direct cytoplasmic H3K9me1 methylation.

Subunit / interactions. Homooligomer. Interacts with SUV39H1 (via SET domain); enhances MECOM transcriptional repression activity. Interacts with CTBP1. Interacts with SMAD3 (via MH2 domain); the interaction is direct. Interacts with SMAD4; through interaction with SMAD3. Interacts with CREBBP, KAT2B and histone deacetylases. Interacts with MAPK8 and MAPK9; inhibits JNK signaling. Interacts (via N-terminus) with RBBP4.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Post-translational modifications. Phosphorylated. May be acetylated by CREBBP and KAT2B.

Disease relevance. A chromosomal aberration involving EVI1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with RUNX1/AML1. Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (RUSAT2) [MIM:616738] An autosomal dominant disease characterized by proximal fusion of the radius and ulna resulting in extremely limited pronation and supination of the forearm, and congenital thrombocytopenia that progresses to pancytopenia. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving MDS1 is found in a form of acute myeloid leukemia (AML). Translocation t(3;21) with AML1.

Domain organisation. Both zinc finger regions are required for the transcriptional activation of PBX1.

Miscellaneous. Produced by alternative promoter usage. Unable to form homooligomers, to interact with CTBP1 and SMAD3 and to repress TGF-beta signaling. Produced by alternative promoter usage.

Isoforms (8)

UniProt ID	Names	Canonical?
Q03112-7	7	yes
Q03112-1	1, Long, Evi-1a
Q03112-3	2, Evi-1c, Mds1/Evi1
Q03112-4	4
Q03112-5	5
Q03112-6	6
Q03112-8	8
Q03112-9	9, MDS1

RefSeq proteins (16): NP_001098547, NP_001098548, NP_001157471, NP_001157472, NP_001192123, NP_001353395, NP_001353396, NP_001353397, NP_001353398, NP_001353399, NP_001353400, NP_001353401, NP_001353402, NP_001353403, NP_004982, NP_005232 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044411	PRDM3_PR-SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF13912, PF21549

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60280)

UniProt features (112 total): cross-link 45, sequence conflict 16, zinc finger region 10, compositionally biased region 10, splice variant 8, region of interest 6, modified residue 5, sequence variant 5, short sequence motif 3, mutagenesis site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6BW3	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03112-F1	51.04	0.00

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 (50): 658, 846, 202, 723, 138, 846, 624, 726, 740, 1037, 1039, 99, 190, 249, 292, 367, 374, 430, 523, 543 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
743–744	partial loss of interaction with ctbp1. loss of interaction with ctbp1; when associated with 586-a-s-775.
774–775	partial loss of interaction with ctbp1. loss of interaction with ctbp1; when associated with 555-a-s-744.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9830364	Formation of the nephric duct
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-6807070	PTEN Regulation
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9830369	Kidney development

MSigDB gene sets: 433 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GGGACCA_MIR133A_MIR133B, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, CCAWYNNGAAR_UNKNOWN, AAGTCCA_MIR422B_MIR422A, KEGG_MAPK_SIGNALING_PATHWAY, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, TGACCTY_ERR1_Q2, FOXO4_01, AP2_Q3, chr3q26, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (14): regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), methylation (GO:0032259), negative regulation of programmed cell death (GO:0043069), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of JNK cascade (GO:0046329), protein maturation (GO:0051604), regulation of cell cycle (GO:0051726), heterochromatin organization (GO:0070828), hematopoietic stem cell proliferation (GO:0071425), chromatin remodeling (GO:0006338), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (14): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), protein homodimerization activity (GO:0042803), histone H3K9 methyltransferase activity (GO:0046974), histone H3 methyltransferase activity (GO:0140938), histone H3K9 monomethyltransferase activity (GO:0140948), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), metal ion binding (GO:0046872), histone H3K9me2 methyltransferase activity (GO:0140947)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), histone deacetylase complex (GO:0000118), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Chromatin modifying enzymes	1
PTEN Regulation	1
Kidney development	1
Intracellular signaling by second messengers	1
Chromatin organization	1
PIP3 activates AKT signaling	1
Signal Transduction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
cellular anatomical structure	3
transcription by RNA polymerase II	2
programmed cell death	2
DNA-templated transcription	2
chromatin organization	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
histone H3K9 methyltransferase activity	2
apoptotic signaling pathway	1
execution phase of apoptosis	1
metabolic process	1
regulation of programmed cell death	1
negative regulation of cellular process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
JNK cascade	1
negative regulation of MAPK cascade	1
regulation of JNK cascade	1
gene expression	1
protein metabolic process	1
cell cycle	1
regulation of cellular process	1
hemopoiesis	1
stem cell proliferation	1
cellular developmental process	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
identical protein binding	1
protein dimerization activity	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	1
histone methyltransferase activity	1

Protein interactions and networks

STRING

1912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MECOM	RUNX1	Q01196	890
MECOM	CTBP1	Q13363	816
MECOM	RPL22	P35268	801
MECOM	RUNX1T1	Q06455	735
MECOM	SMAD3	P84022	715
MECOM	KAT2B	Q92831	712
MECOM	GATA2	P23769	676
MECOM	ETV6	P41212	673
MECOM	SETBP1	Q9Y6X0	670
MECOM	COX7B2	Q8TF08	649
MECOM	RPN1	P04843	642
MECOM	CEBPA	P49715	642
MECOM	GATA1	P15976	641
MECOM	ZFPM2	Q8WW38	640
MECOM	BPIFA1	Q9NP55	635

IntAct

49 interactions, top by confidence:

A	B	Type	Score
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
MECOM	RBBP4	psi-mi:“MI:0914”(association)	0.650
MECOM	RBBP4	psi-mi:“MI:0407”(direct interaction)	0.650
RBBP4	MECOM	psi-mi:“MI:0407”(direct interaction)	0.650
MECOM	Ctbp2	psi-mi:“MI:0915”(physical association)	0.630
UXT	MECOM	psi-mi:“MI:0915”(physical association)	0.590
MECOM	UXT	psi-mi:“MI:0915”(physical association)	0.590
MECOM	UXT	psi-mi:“MI:0407”(direct interaction)	0.590
UXT	MECOM	psi-mi:“MI:0407”(direct interaction)	0.590
MECOM	RABGAP1L	psi-mi:“MI:0915”(physical association)	0.570
ERMAP	AP3B1	psi-mi:“MI:0914”(association)	0.530
MECOM	FOS	psi-mi:“MI:0915”(physical association)	0.500
MECOM	FOS	psi-mi:“MI:0914”(association)	0.500
PIK3R3	MECOM	psi-mi:“MI:0915”(physical association)	0.490
MECOM	PIK3R3	psi-mi:“MI:0915”(physical association)	0.490
SIRT1	MECOM	psi-mi:“MI:0915”(physical association)	0.400
	MECOM	psi-mi:“MI:0915”(physical association)	0.370
MECOM		psi-mi:“MI:0915”(physical association)	0.370
PRMT1	MECOM	psi-mi:“MI:0915”(physical association)	0.370
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (481): MECOM (Biochemical Activity), MECOM (Affinity Capture-MS), MECOM (Affinity Capture-MS), NLRP14 (Co-fractionation), MECOM (Two-hybrid), MECOM (Two-hybrid), MECOM (Affinity Capture-Luminescence), MECOM (Proximity Label-MS), MECOM (Affinity Capture-Western), HIC1 (Affinity Capture-Western), MECOM (FRET), MECOM (Affinity Capture-MS), MECOM (Affinity Capture-MS), MECOM (Affinity Capture-MS), MECOM (Affinity Capture-MS)

ESM2 similar proteins: A0JPB4, A1L1J6, A1L1R6, A1Z9R4, A2A935, A4IFJ6, E9Q6W4, E9Q8T2, G5E8B9, O08961, O13089, O15060, O42410, O57415, O73590, O95625, P14404, P57071, Q03112, Q03267, Q09452, Q13422, Q1L8W0, Q2M1K9, Q5DU09, Q5R9W9, Q5T0B9, Q5ZLR2, Q60821, Q62947, Q64318, Q6DBW0, Q6GNP2, Q6INV8, Q6KAS7, Q6NRM0, Q6NUD7, Q7TS63, Q802Y8, Q80TS5

Diamond homologs: A0A163UT06, A2A935, A2AGX3, A2AJ77, B8A5Y1, E9Q3T6, O75626, P0C6Y7, P14404, Q03112, Q13029, Q3UZD5, Q60636, Q63755, Q6P2A1, Q8BZ97, Q96EQ9, Q9GZV8, Q9H4Q4, Q9HAZ2, Q9NQV5, Q9NQV7, Q9NQV8, Q9NQW5, B7ZRM8, B7ZRU9, Q22024, Q8I7Z8, B1WBU4, A6QPM3, Q9NQX0, Q9NQX1, P80944, Q29419, Q7TS63, Q9CXE0, Q9P243, Q3US17, E9Q8T2, P57071

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
MECOM	“up-regulates quantity by expression”	PBX1	“transcriptional regulation”
RUNX1	“up-regulates quantity by expression”	MECOM	“transcriptional regulation”
MECOM	“up-regulates quantity by expression”	GATA2	“transcriptional regulation”
Ub:E2	“up-regulates activity”	MECOM	ubiquitination
MECOM	down-regulates	SMAD3	binding
MECOM	“down-regulates activity”	RUNX1	binding
MLL-AF9	“up-regulates quantity by expression”	MECOM	methylation
“MLL Fusion”	“up-regulates quantity by expression”	MECOM	methylation
MECOM	“up-regulates quantity by expression”	ANGPT1	“transcriptional regulation”
MECOM	“up-regulates quantity by expression”	ANGPT2	“transcriptional regulation”
MECOM	“up-regulates quantity by expression”	GATA1	“transcriptional regulation”
MECOM	“up-regulates quantity by expression”	TEK	“transcriptional regulation”
CDK2	“up-regulates activity”	MECOM	phosphorylation
CSNK2A1	“up-regulates activity”	MECOM	phosphorylation
PPP1CA	“down-regulates activity”	MECOM	dephosphorylation
CDK3	“up-regulates activity”	MECOM	phosphorylation
MECOM	“up-regulates activity”	DNMT3A	binding
ATM	“up-regulates activity”	MECOM	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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
Regulation of PTEN gene transcription	5	33.0×	2e-05
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	32.5×	5e-06
Negative Regulation of CDH1 Gene Transcription	6	26.7×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
chromatin organization	5	13.4×	1e-03
chromatin remodeling	5	9.9×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — BRCA, MEL, PRAD, UCEC.

Clinical variants and AI predictions

ClinVar

1747 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	21
Uncertain significance	1074
Likely benign	548
Benign	18

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1188840	NM_004991.4(MECOM):c.2849G>C (p.Arg950Thr)	Pathogenic
1334182	NM_004991.4(MECOM):c.2905C>T (p.Arg969Cys)	Pathogenic
1334186	NM_004991.4(MECOM):c.2906G>A (p.Arg969His)	Pathogenic
1454043	NM_004991.4(MECOM):c.1692del (p.Ser565fs)	Pathogenic
218951	NM_004991.4(MECOM):c.2830A>G (p.Thr944Ala)	Pathogenic
218952	NM_004991.4(MECOM):c.2816A>G (p.His939Arg)	Pathogenic
2506775	NM_004991.4(MECOM):c.2813G>A (p.Arg938Gln)	Pathogenic
2664376	NM_004991.4(MECOM):c.2861G>C (p.Cys954Ser)	Pathogenic
2910177	NM_004991.4(MECOM):c.633C>A (p.Cys211Ter)	Pathogenic
3062716	GRCh37/hg19 3q26.2(chr3:168744704-168855633)x1	Pathogenic
3341141	NM_004991.4(MECOM):c.2117_2120del (p.Ser706fs)	Pathogenic
3359122	NM_004991.4(MECOM):c.627T>A (p.Tyr209Ter)	Pathogenic
3768768	NM_004991.4(MECOM):c.2592_2598del (p.Asp864fs)	Pathogenic
3900735	NM_004991.4(MECOM):c.655G>T (p.Glu219Ter)	Pathogenic
3900736	NM_004991.4(MECOM):c.2860T>C (p.Cys954Arg)	Pathogenic
3900740	NM_004991.4(MECOM):c.2504_2505del (p.Lys835fs)	Pathogenic
3900741	NM_004991.4(MECOM):c.2528T>G (p.Leu843Ter)	Pathogenic
3900743	NM_004991.4(MECOM):c.2850-1G>A	Pathogenic
620298	NM_004991.4(MECOM):c.3106C>T (p.Arg1036Ter)	Pathogenic
1334183	NM_004991.4(MECOM):c.2893C>G (p.Gln965Glu)	Likely pathogenic
1334185	NM_004991.4(MECOM):c.2906G>T (p.Arg969Leu)	Likely pathogenic
1334187	NM_004991.4(MECOM):c.2912T>C (p.Ile971Thr)	Likely pathogenic
1676728	NM_004991.4(MECOM):c.2398A>T (p.Lys800Ter)	Likely pathogenic
1703774	NM_004991.4(MECOM):c.739C>T (p.Gln247Ter)	Likely pathogenic
2500844	NM_004991.4(MECOM):c.2772-4A>G	Likely pathogenic
3252937	NM_004991.4(MECOM):c.2803A>G (p.Asn935Asp)	Likely pathogenic
3602676	NM_004991.4(MECOM):c.2836G>A (p.Glu946Lys)	Likely pathogenic
3633042	NM_004991.4(MECOM):c.613+1G>C	Likely pathogenic
3775584	NM_004991.4(MECOM):c.2842C>G (p.Pro948Ala)	Likely pathogenic
3900737	NM_004991.4(MECOM):c.2873T>C (p.Phe958Ser)	Likely pathogenic

SpliceAI

2644 predictions. Top by Δscore:

Variant	Effect	Δscore
3:169088994:CTGTA:C	donor_loss	1.0000
3:169088995:TGTAC:T	donor_loss	1.0000
3:169088996:GTAC:G	donor_loss	1.0000
3:169088997:TA:T	donor_loss	1.0000
3:169088999:C:CT	donor_loss	1.0000
3:169089181:TACC:T	acceptor_loss	1.0000
3:169089182:ACCT:A	acceptor_loss	1.0000
3:169089184:C:CA	acceptor_loss	1.0000
3:169089996:TCA:T	donor_loss	1.0000
3:169089998:A:AC	donor_gain	1.0000
3:169089999:C:CC	donor_gain	1.0000
3:169089999:CCT:C	donor_gain	1.0000
3:169089999:CCTCA:C	donor_gain	1.0000
3:169090233:CATT:C	acceptor_gain	1.0000
3:169090237:C:CC	acceptor_gain	1.0000
3:169090238:T:C	acceptor_gain	1.0000
3:169090241:C:CT	acceptor_gain	1.0000
3:169090242:A:T	acceptor_gain	1.0000
3:169090247:C:CT	acceptor_gain	1.0000
3:169090248:A:C	acceptor_gain	1.0000
3:169090249:T:TC	acceptor_gain	1.0000
3:169092952:CTTTA:C	donor_loss	1.0000
3:169092953:TTTAC:T	donor_loss	1.0000
3:169092954:TTA:T	donor_loss	1.0000
3:169092955:TACCT:T	donor_loss	1.0000
3:169092956:A:AC	donor_gain	1.0000
3:169092956:A:AT	donor_loss	1.0000
3:169092957:C:CC	donor_gain	1.0000
3:169092957:C:T	donor_loss	1.0000
3:169092957:CCT:C	donor_gain	1.0000

AlphaMissense

8304 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:169095105:A:G	L988P	1.000
3:169095107:G:C	H987Q	1.000
3:169095107:G:T	H987Q	1.000
3:169095108:T:C	H987R	1.000
3:169095108:T:G	H987P	1.000
3:169095109:G:C	H987D	1.000
3:169095109:G:T	H987N	1.000
3:169095117:A:G	L984S	1.000
3:169095119:A:C	N983K	1.000
3:169095119:A:T	N983K	1.000
3:169095132:C:T	G979D	1.000
3:169095134:A:C	F978L	1.000
3:169095134:A:T	F978L	1.000
3:169095135:A:G	F978S	1.000
3:169095136:A:G	F978L	1.000
3:169095146:A:C	C974W	1.000
3:169095147:C:A	C974F	1.000
3:169095147:C:G	C974S	1.000
3:169095147:C:T	C974Y	1.000
3:169095148:A:G	C974R	1.000
3:169095148:A:T	C974S	1.000
3:169095155:A:C	C971W	1.000
3:169095156:C:A	C971F	1.000
3:169095156:C:G	C971S	1.000
3:169095156:C:T	C971Y	1.000
3:169095157:A:G	C971R	1.000
3:169095157:A:T	C971S	1.000
3:169095161:A:C	F969L	1.000
3:169095161:A:T	F969L	1.000
3:169095162:A:G	F969S	1.000

dbSNP variants (sampled 300 via entrez): RS1000000858 (3:169119448 G>C), RS1000004185 (3:169430927 T>C), RS1000008926 (3:169512890 A>G), RS1000011700 (3:169471309 T>A,C), RS1000021701 (3:169300702 C>A,T), RS1000022123 (3:169646368 C>T), RS1000035227 (3:169471470 A>G), RS1000040203 (3:169213943 G>A,C), RS1000042860 (3:169297034 T>A), RS1000045023 (3:169171049 T>C), RS1000046365 (3:169349406 C>A,T), RS1000048344 (3:169203012 T>A), RS1000053459 (3:169384411 C>G,T), RS1000054108 (3:169126444 A>T), RS1000054740 (3:169646485 TA>T)

Disease associations

OMIM: gene MIM:165215 | disease phenotypes: MIM:616738, MIM:605432, MIM:127550

GenCC curated gene-disease

Disease	Classification	Inheritance
radioulnar synostosis with amegakaryocytic thrombocytopenia 2	Definitive	Autosomal dominant
MECOM-associated syndrome	Definitive	Autosomal dominant
radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
MECOM-associated syndrome	Definitive	AD

Mondo (11): radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (MONDO:0014758), congenital radioulnar synostosis (MONDO:0017985), MECOM-associated syndrome (MONDO:0100458), hereditary neoplastic syndrome (MONDO:0015356), radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (MONDO:0024558), congenital heart disease (MONDO:0005453), malignant peritoneal mesothelioma (MONDO:0005512), thrombocytopenia (MONDO:0002049), dyskeratosis congenita, autosomal dominant 1 (MONDO:0007485), primary ovarian failure (MONDO:0005387), radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (MONDO:0011555)

Orphanet (6): Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (Orphanet:71289), Isolated radio-ulnar synostosis (Orphanet:3269), Inherited cancer-predisposing syndrome (Orphanet:140162), Malignant peritoneal mesothelioma (Orphanet:168811), Dyskeratosis congenita (Orphanet:1775), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000034	Hydrocele testis
HP:0000175	Cleft palate
HP:0000407	Sensorineural hearing impairment
HP:0001256	Mild intellectual disability
HP:0001385	Hip dysplasia
HP:0001433	Hepatosplenomegaly
HP:0001789	Hydrops fetalis
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001903	Anemia
HP:0001905	Congenital thrombocytopenia
HP:0002974	Radioulnar synostosis
HP:0004209	Clinodactyly of the 5th finger
HP:0004859	Amegakaryocytic thrombocytopenia
HP:0006101	Finger syndactyly
HP:0006394	Limited pronation/supination of forearm
HP:0009295	Short middle phalanx of the 4th finger
HP:0010557	Overlapping fingers

GWAS associations

112 associations (top):

Study	Trait	p-value
GCST000393_2	Systolic blood pressure	1.000000e-07
GCST000394_5	Diastolic blood pressure	8.000000e-08
GCST000687_3	Nasopharyngeal carcinoma	1.000000e-08
GCST000756_4	Magnesium levels	1.000000e-08
GCST001166_4	Aging (time to event)	3.000000e-06
GCST001227_8	Systolic blood pressure	2.000000e-13
GCST001228_7	Diastolic blood pressure	2.000000e-12
GCST001236_26	Blood pressure	8.000000e-13
GCST001251_12	Pulmonary function	3.000000e-08
GCST001533_1	Immune reponse to smallpox (secreted IL-1beta)	4.000000e-07
GCST001610_1	Renal function-related traits (BUN)	3.000000e-14
GCST001784_47	Pulmonary function (smoking interaction)	4.000000e-06
GCST001830_1	Osteoporosis	4.000000e-08
GCST002587_6	Blood pressure (smoking interaction)	7.000000e-08
GCST002840_2	Myeloproliferative neoplasms	2.000000e-09
GCST002986_5	Childhood and early adolescence aggressive behavior	4.000000e-06
GCST003488_9	Response to fenofibrate (triglyceride levels)	5.000000e-06
GCST003815_83	Late-onset Alzheimer’s disease	9.000000e-07
GCST004185_17	Lung function (FEV1/FVC)	6.000000e-14
GCST004601_48	Red blood cell count	3.000000e-11
GCST004603_254	Platelet count	4.000000e-15
GCST004604_89	Hematocrit	9.000000e-10
GCST004607_259	Plateletcrit	5.000000e-24
GCST004607_260	Plateletcrit	1.000000e-22
GCST004776_15	Systolic blood pressure	2.000000e-11
GCST004777_3	Diastolic blood pressure	3.000000e-12
GCST004780_3	Cortisol levels (saliva)	2.000000e-07
GCST005113_2	Nasopharyngeal carcinoma	2.000000e-12
GCST005580_286	Intraocular pressure	1.000000e-09
GCST005580_58	Intraocular pressure	3.000000e-12

EFO canonical traits (44, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004845	magnesium measurement
EFO:0022597	aging
EFO:0006340	mean arterial pressure
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0006526	pack-years measurement
EFO:0004251	myeloproliferative disorder
EFO:0007681	triglyceride change measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0004713	FEV/FVC ratio
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004348	hematocrit
EFO:0007985	platelet crit
EFO:0005843	cortisol measurement
EFO:0004695	intraocular pressure measurement
EFO:0007701	spine bone mineral density
EFO:0004527	mean corpuscular hemoglobin
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0004312	vital capacity
EFO:0005301	reading and spelling ability
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009944	Antiglaucoma preparations and miotics use measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C565079	Dyskeratosis Congenita, Autosomal Dominant (supp.)
C562408	Radioulnar Synostosis (supp.)
C565328	Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5214865 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases localization, increases sumoylation, increases response to substance, decreases expression, affects cotreatment	5
sodium arsenite	affects methylation, decreases expression, increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	increases methylation, affects expression, affects methylation, decreases methylation	3
Tretinoin	increases expression, increases stability	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
entinostat	decreases expression, increases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	affects methylation, increases methylation	2
Aflatoxin B1	affects methylation, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
TAK-243	increases sumoylation	1
quinone	decreases phosphorylation, affects reaction, decreases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
arsenite	decreases methylation	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
2-palmitoylglycerol	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
asparanin A	decreases expression	1
NSC668394	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	affects response to substance	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
CHEMBL5214666	Binding	Selectivity interaction (Methyltransferase panel (DSF assay)) EUB0000234b MECOM	Selectivity Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4B3	SEES3-1V human MECOM, clone1	Embryonic stem cell	Male
CVCL_A4B4	SEES3-1V human MECOM, clone2	Embryonic stem cell	Male
CVCL_A4B5	SEES3-1V human MECOM, clone3	Embryonic stem cell	Male
CVCL_A5ZK	U937/EVI1	Cancer cell line	Male
CVCL_B8K8	Abcam HCT 116 MECOM KO	Cancer cell line	Male
CVCL_B8YQ	Abcam MCF-7 MECOM KO	Cancer cell line	Female
CVCL_B9MH	Abcam A-549 MECOM KO	Cancer cell line	Male
CVCL_E0HU	Ubigene HeLa MECOM KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE