EML4

Summary

EML4 (EMAP like 4, HGNC:1316) is a protein-coding gene on chromosome 2p21, encoding Echinoderm microtubule-associated protein-like 4 (Q9HC35). Essential for the formation and stability of microtubules (MTs).

This gene is a member of the echinoderm microtubule associated protein-like family. The encoded WD-repeat protein may be involved in microtubule formation. Abnormal fusion of parts of this gene with portions of the anaplastic lymphoma receptor tyrosine kinase gene, which generates EML4-ALK fusion transcripts, is one of the primary mutations associated with non-small cell lung cancer. Alternative splicing of this gene results in two transcript variants.

Source: NCBI Gene 27436 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 194 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_019063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1316
Approved symbol	EML4
Name	EMAP like 4
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	ROPP120, ELP120
Ensembl gene	ENSG00000143924
Ensembl biotype	protein_coding
OMIM	607442
Entrez	27436

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000318522, ENST00000401738, ENST00000402711, ENST00000406175, ENST00000409040, ENST00000472632, ENST00000480320, ENST00000482660, ENST00000862356, ENST00000862357, ENST00000921467, ENST00000921468, ENST00000921469, ENST00000921470, ENST00000921471, ENST00000921472, ENST00000921473, ENST00000921474, ENST00000921475, ENST00000963712, ENST00000963713

RefSeq mRNA: 3 — MANE Select: NM_019063 NM_001145076, NM_001410776, NM_019063

CCDS: CCDS1807, CCDS46266, CCDS92747

Canonical transcript exons

ENST00000318522 — 23 exons

Exon	Start	End
ENSE00000962691	42261121	42261294
ENSE00000962694	42280850	42280973
ENSE00000962695	42282823	42282972
ENSE00001548738	42169353	42169636
ENSE00001665541	42264706	42264731
ENSE00001779613	42263178	42263306
ENSE00003465520	42303104	42303229
ENSE00003530355	42304484	42304551
ENSE00003554806	42295381	42295516
ENSE00003596619	42256501	42256630
ENSE00003601847	42317427	42317524
ENSE00003608258	42329734	42332548
ENSE00003615295	42326154	42326252
ENSE00003621165	42284634	42284703
ENSE00003621553	42325467	42325554
ENSE00003642723	42245505	42245687
ENSE00003652501	42303315	42303446
ENSE00003656184	42315962	42316050
ENSE00003665705	42295125	42295259
ENSE00003676844	42288227	42288322
ENSE00003686040	42328886	42329016
ENSE00003686237	42286269	42286379
ENSE00003686987	42301241	42301392

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 96.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.0886 / max 788.3649, expressed in 1802 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19918	33.4275	1799
19919	1.9333	577
19921	0.5060	275
19920	0.2217	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	96.02	gold quality
jejunal mucosa	UBERON:0000399	95.59	gold quality
visceral pleura	UBERON:0002401	94.80	gold quality
tonsil	UBERON:0002372	94.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.43	gold quality
colonic mucosa	UBERON:0000317	94.38	gold quality
epithelium of nasopharynx	UBERON:0001951	94.32	gold quality
adrenal tissue	UBERON:0018303	94.12	gold quality
duodenum	UBERON:0002114	94.06	gold quality
rectum	UBERON:0001052	93.29	gold quality
pylorus	UBERON:0001166	93.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.48	gold quality
parotid gland	UBERON:0001831	92.35	gold quality
spleen	UBERON:0002106	92.35	gold quality
lymph node	UBERON:0000029	92.34	gold quality
parietal pleura	UBERON:0002400	92.33	gold quality
germinal epithelium of ovary	UBERON:0001304	92.22	gold quality
body of pancreas	UBERON:0001150	92.17	gold quality
upper leg skin	UBERON:0004262	92.14	gold quality
pleura	UBERON:0000977	91.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.68	gold quality
small intestine	UBERON:0002108	91.61	gold quality
bone marrow	UBERON:0002371	91.57	gold quality
gingival epithelium	UBERON:0001949	91.52	gold quality
mammalian vulva	UBERON:0000997	91.28	gold quality
gall bladder	UBERON:0002110	91.27	gold quality
cardia of stomach	UBERON:0001162	91.12	gold quality
right lobe of liver	UBERON:0001114	90.95	gold quality
endometrium	UBERON:0001295	90.90	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	1508.34
E-HCAD-13	yes	707.18
E-MTAB-8142	yes	85.58
E-GEOD-135922	yes	27.20
E-CURD-122	yes	26.00
E-CURD-46	yes	16.94
E-HCAD-25	yes	15.24
E-ANND-3	yes	11.97
E-CURD-112	yes	9.10
E-MTAB-6678	yes	6.71
E-MTAB-6379	no	3753.03
E-GEOD-124858	no	1495.63
E-MTAB-7606	no	771.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting EML4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-605-3P	99.88	69.22	1833

Literature-anchored findings (GeneRIF, showing 40)

• EML4 negative cells showed a completely modified microtubule network, indicating that EML4 is necessary for correct microtubule formation. (PMID:16890222)
• EML4 is part of a fusion protein linked to histological characteristics in a subset of lung neoplasms. (PMID:18166835)
• EML4-ALK fusion gene product is involved in the carcinogenesis in non-small cell lung carcinomas (PMID:18242762)
• EML4-ALK fusions occur in less than 3% of non-small cell lung cancers samples; EML4 and/or ALK amplifications also occur. (PMID:18320074)
• EML4-ALK fusion transcript is not present in gastrointestinal or breast cancers and is specific to NSCLC. (PMID:18414414)
• A lung cancer cell line expressing endogenous variant 3 of EML4-ALK underwent cell death on exposure to a specific inhibitor of ALK catalytic activity. (PMID:18593892)
• EML4-ALK fusion gene is expressed in lung cancer (PMID:18594010)
• Genomic rearrangements accompanying the EML4-ALK fusion is associated with non-small cell lung cancer. (PMID:18927303)
• The EML4-ALK transcript cannot be regarded as a specific diagnostic tool for non-small cell lung cancer. (PMID:19147828)
• Data show that compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger and were more likely to be men. (PMID:19667264)
• The presence of an EML-ALK rearrangement was verified by identifying genomic fusion points in tumor samples representative of breast, colon, and NSCLC. (PMID:19737969)
• EML4-ALK fusion genes are associated with non-small-cell lung cancer. (PMID:20183914)
• It was discovered that about 5% of cases with non-small cell lung cancer, a new active fused kinase EMLA4-ALK is generated.Its use in molecular targeted therapy is promising. (PMID:20578368)
• EML4-ALK fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of EML4-ALK-positive patients (PMID:20624322)
• frequent rearrangement in lung signet-ring cell carcinoma (PMID:21036415)
• EML4-ALK fusion variants have a role in non-small cell lung cancer (PMID:21356191)
• New molecular targets are on investigation, such as EML4-ALK translocation. (PMID:21420271)
• EML4-ALK and low thymidylate synthase expression is associated with treatment outcome with pemetrexed in Non-Small Cell Lung Cancer. (PMID:22056890)
• EML4-anaplastic lymphoma kinase (ALK) fusion gene is associated with longer overall survival of lung adenocarcinoma patients with wild-type epidermal growth factor receptor mutations. (PMID:22124476)
• EML4-ALK variant is associated with lung cancer. (PMID:22706607)
• EML4-ALK-variations are associated with non-small cell lung cancer. (PMID:22722791)
• Lung neoplasm patients who harbor EML4-ALK fusion genes generally have wild type EGFR and KRAS genes. (PMID:22736493)
• variations in EML4-ALK fusion is associated with small-cell lung cancer with adenocarcinoma. (PMID:23154565)
• EML4-ALK fusion variant is associated with non-small-cell lung cancer. (PMID:23169500)
• The prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with non-small cell lung cancer, is reported. (PMID:23341890)
• EML4-ALK rearrangement is associated with congenital pulmonary airway malformation. (PMID:23357247)
• EML4-ALK rearrangements are associated with lung carcinomas. (PMID:23408463)
• EML4-ALK rearrangement is associated with response to therapy in lung adenocarcinoma. (PMID:23486270)
• The first report concerning the presence of the EML4-ALK fusion gene in a sarcomatoid carcinoma of the lung. (PMID:23664446)
• EML4-ALK gene rearrangements do not appear to be involved in the development of primary adenocarcinoma of the urinary bladder. (PMID:23887300)
• evaluated mutations in four driver genes, epidermal growth factor receptor (EGFR), Kirsten ras oncogene (KRAS), c-MET, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), in Chinese lung adenocarcinoma patients (PMID:23919423)
• This case suggests that echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion is an oncogenic event in not only carcinomas but also sarcomas originating from stromal cells. (PMID:24277751)
• EML4-ALK fusion is uncommon, reported in about 5% of NSCLC patients. (PMID:24346098)
• EML4-ALK fusion genepositivitymightbe higher inyoungerNSCLCpatientswithwild-type EGFR. (PMID:24388371)
• EML4 genetic translocation is a therapeutic target in the treatment of aggressive papillary cancer of the thyroid. (PMID:24633422)
• Hsp90-sensitive EML4-ALK variants are exceptions to the rule that oncogenic fusion proteins involve breakpoints in disordered regions of both partners (PMID:24706829)
• EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. (PMID:24935562)
• Results suggest that heat shock protein 90 (Hsp90) inhibitors may overcome ligand-triggered resistance in microtubule associated protein-like 4 (EML4)–anaplastic lymphoma kinase (ALK) lung cancer cells. (PMID:24952482)
• NSCLC patients with the EML4-ALK fusion gene might be relatively insensitivite to cytotoxic chemotherapy. (PMID:24982409)
• Letter/Case Report: lung adenocarcinoma where EML4-ALK gene rearrangement was missed by FISH techniques but detected using reverse transcriptase PCR. (PMID:25028527)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	EML4	ENSDARG00000109443
mus_musculus	Eml4	ENSMUSG00000032624
rattus_norvegicus	Eml4	ENSRNOG00000030294

Paralogs (9): EML1 (ENSG00000066629), EML2 (ENSG00000125746), EML3 (ENSG00000149499), CFAP251 (ENSG00000158023), WDR90 (ENSG00000161996), EML5 (ENSG00000165521), CFAP52 (ENSG00000166596), CFAP44 (ENSG00000206530), EML6 (ENSG00000214595)

Protein

Protein identifiers

Echinoderm microtubule-associated protein-like 4 — Q9HC35 (reviewed: Q9HC35)

Alternative names: Restrictedly overexpressed proliferation-associated protein, Ropp 120

All UniProt accessions (2): Q9HC35, B5MBZ0

UniProt curated annotations — full annotation on UniProt →

Function. Essential for the formation and stability of microtubules (MTs). Required for the organization of the mitotic spindle and for the proper attachment of kinetochores to MTs. Promotes the recruitment of NUDC to the mitotic spindle for mitotic progression.

Subunit / interactions. Homotrimer; self-association is mediated by the N-terminal coiled coil. Interacts (via WD repeats) with NUDC. Interacts with alpha- and beta-tubulin during mitosis.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Microtubule organizing center. Midbody.

Post-translational modifications. Phosphorylated during mitosis. Phosphorylation at Ser-144 and Ser-146 promotes its dissociation from microtubules during mitosis which is required for efficient chromosome congression.

Disease relevance. A chromosomal aberration involving EML4 has been identified in a subset of patients with non-small-cell lung carcinoma. This aberration leads to the production of a fusion protein between the N-terminus of EML4 and the C-terminus of ALK. It is unclear whether the fusion protein is caused by a simple inversion within 2p (inv(2)(p21p23)) or whether the chromosome translocation involving 2p is more complex. When tested in a heterologous system, the fusion protein EML4-ALK possesses transforming activity that is dependent on ALK catalytic activity, possibly due to spontaneous dimerization mediated by the EML4 moiety, leading to ALK kinase activation.

Similarity. Belongs to the WD repeat EMAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HC35-1	1	yes
Q9HC35-2	2

RefSeq proteins (3): NP_001138548, NP_001397705, NP_061936* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR005108	HELP	Conserved_site
IPR011047	Quinoprotein_ADH-like_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050630	WD_repeat_EMAP	Family
IPR055439	Beta-prop_EML_1st	Domain
IPR055442	Beta-prop_EML-like_2nd	Domain

Pfam: PF03451, PF23409, PF23414

UniProt features (61 total): modified residue 23, repeat 13, compositionally biased region 6, region of interest 4, sequence variant 4, mutagenesis site 4, site 2, chain 1, coiled-coil region 1, splice variant 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4CGC	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC35-F1	77.66	0.63

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 (2): 496–497 (breakpoint for translocation to form the eml4-alk fusion protein (variant 1)); 747–748 (breakpoint for translocation to form the eml4-alk fusion protein (variant 2))

Post-translational modifications (23): 1, 7, 13, 16, 61, 96, 134, 144, 146, 171, 200, 201, 226, 237, 490, 609, 891, 895, 897, 899 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
144	phosphorylation-deficient mutant which shows increased localization to microtubules during mitosis, increased microtubul
144	phosphomimetic mutant which shows reduced localization to microtubules during interphase; when associated with d-146.
146	phosphorylation-deficient mutant which shows increased localization to microtubules during mitosis, increased microtubul
146	phosphomimetic mutant which shows reduced localization to microtubules during interphase; when associated with d-144.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9700645	ALK mutants bind TKIs
R-HSA-9725370	Signaling by ALK fusions and activated point mutants

MSigDB gene sets: 259 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_CHROMOSOME_LOCALIZATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, SRF_Q5_01, AGTCTTA_MIR499, TCF4_Q5, SRF_C

GO Biological Process (6): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), microtubule-based process (GO:0007017), mitotic metaphase chromosome alignment (GO:0007080), attachment of spindle microtubules to kinetochore (GO:0008608), cell division (GO:0051301)

GO Molecular Function (4): microtubule binding (GO:0008017), alpha-tubulin binding (GO:0043014), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (16): cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), microtubule (GO:0005874), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), midbody (GO:0030496), perinuclear theca (GO:0033011), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), sperm annulus (GO:0097227), sperm principal piece (GO:0097228), sperm glycocalyx (GO:0120238), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by ALK in cancer	2
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
tubulin binding	3
microtubule cytoskeleton	3
cellular process	2
metaphase chromosome alignment	2
cytoskeleton	2
sperm flagellum	2
intracellular membraneless organelle	2
cytoskeleton organization	1
microtubule-based process	1
cell cycle	1
mitotic nuclear division	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
mitotic cell cycle process	1
microtubule binding	1
cell cycle process	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
perinuclear region of cytoplasm	1
spindle	1
glycocalyx	1

Protein interactions and networks

STRING

2625 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EML4	ALK	Q9UM73	997
EML4	ROS1	P08922	921
EML4	EGFR	P00533	904
EML4	RET	P07949	822
EML4	KIF5B	P33176	807
EML4	KRAS	P01116	795
EML4	NPM1	P06748	757
EML4	NTRK1	P04629	741
EML4	NTRK3	Q16288	734
EML4	BRAF	P15056	729
EML4	RET	P07949	692
EML4	KLC1	Q07866	682
EML4	TPM4	P07226	676
EML4	DDR2	Q16832	669
EML4	STRN	O43815	668

IntAct

91 interactions, top by confidence:

A	B	Type	Score
NEK9	DYNLL1	psi-mi:“MI:0914”(association)	0.900
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
TUBB	PLD2	psi-mi:“MI:0914”(association)	0.640
PHKG2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
MIA2	RGPD8	psi-mi:“MI:0914”(association)	0.640
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
TKT	POTEF	psi-mi:“MI:0914”(association)	0.530
MIA2	RGPD3	psi-mi:“MI:0914”(association)	0.530
TUBB2A	EML2	psi-mi:“MI:0914”(association)	0.530
TUBB2B	EML2	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530
TUBB2A	ARL2	psi-mi:“MI:0914”(association)	0.530
NEK7	P4HA2	psi-mi:“MI:0914”(association)	0.510
	AP3D1	psi-mi:“MI:0914”(association)	0.460
Nek9	EML1	psi-mi:“MI:0914”(association)	0.350
TFEB	PPM1G	psi-mi:“MI:0914”(association)	0.350
	ABL1	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
TUBB3	EML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (182): EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS), EML4 (Proximity Label-MS), EML4 (Proximity Label-MS), EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS), NUDC (Affinity Capture-Western), EML4 (Affinity Capture-Western), EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS), EML4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KIZ8, A0A1L8GXY4, A0A571BF63, A0A8M9QN10, A2CEI4, A2RRP1, A4D1P6, A6H8T2, A9X1C6, B0FXQ5, B1WC10, B2KIQ4, B2RY71, B2RYI0, B7FF09, B7FF12, E9PYY5, F1QHZ6, Q1LXZ7, Q2HJE1, Q3UMY5, Q402B2, Q4V8G4, Q5R6T6, Q5RE88, Q5U1Z0, Q5VTH9, Q5XIZ9, Q5ZLL7, Q6DFC6, Q6DTM3, Q6GPB9, Q6P2C0, Q6TEN6, Q7TMQ7, Q7ZVR1, Q8BMG7, Q8BX17, Q8C147, Q8IWG1

Diamond homologs: O00423, O95834, Q05BC3, Q05BV3, Q26613, Q2TAF3, Q32P44, Q3UMY5, Q4V8C3, Q5SQM0, Q6DIP5, Q6ED65, Q6P6T4, Q6ZMW3, Q7TNG5, Q8BQM8, Q8VC03, Q9HC35, Q9N9X3, Q9VUI3, Q9Y1C1, B3MC74, B4JW81, B4KTK4, B4LJT7, B4MY77, P29829, Q9NFZ1, B6K1G6, O48847, Q15542, Q8C092, O22212, O45487, O75083, O88342, O93277, Q2KJH4, Q5RKI0, Q86HX1

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NEK6	“down-regulates activity”	EML4	phosphorylation
NEK7	“down-regulates activity”	EML4	phosphorylation
NEK6	“up-regulates activity”	EML4	phosphorylation
NEK7	“up-regulates activity”	EML4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	8	58.0×	2e-11
Transport of connexons to the plasma membrane	8	58.0×	2e-11
Activation of AMPK downstream of NMDARs	10	50.8×	4e-13
Gap junction trafficking and regulation	8	50.8×	6e-11
Gap junction trafficking	8	50.8×	6e-11
Post-chaperonin tubulin folding pathway	8	50.8×	6e-11
Formation of tubulin folding intermediates by CCT/TriC	8	45.1×	1e-10
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	8	43.5×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	7	18.5×	3e-05
mitotic cell cycle	12	15.6×	1e-08
microtubule cytoskeleton organization	12	14.1×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	151
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

5221 predictions. Top by Δscore:

Variant	Effect	Δscore
2:42245496:A:AG	acceptor_gain	1.0000
2:42245497:T:G	acceptor_gain	1.0000
2:42245499:TTATA:T	acceptor_gain	1.0000
2:42245500:TATAG:T	acceptor_gain	1.0000
2:42245501:A:AG	acceptor_gain	1.0000
2:42245501:ATAGA:A	acceptor_gain	1.0000
2:42245502:T:G	acceptor_gain	1.0000
2:42245502:TAG:T	acceptor_gain	1.0000
2:42245503:A:AG	acceptor_gain	1.0000
2:42245503:AGAT:A	acceptor_gain	1.0000
2:42245503:AGATG:A	acceptor_gain	1.0000
2:42245504:G:GT	acceptor_gain	1.0000
2:42245504:G:T	acceptor_gain	1.0000
2:42245504:GA:G	acceptor_gain	1.0000
2:42245504:GAT:G	acceptor_gain	1.0000
2:42245504:GATG:G	acceptor_gain	1.0000
2:42245504:GATGA:G	acceptor_gain	1.0000
2:42245676:TCTC:T	donor_gain	1.0000
2:42245683:TAAAG:T	donor_loss	1.0000
2:42245684:AAAG:A	donor_loss	1.0000
2:42245686:AG:A	donor_loss	1.0000
2:42245688:GT:G	donor_loss	1.0000
2:42245689:T:A	donor_loss	1.0000
2:42261305:TCCCC:T	donor_gain	1.0000
2:42263176:A:AG	acceptor_gain	1.0000
2:42263177:G:GG	acceptor_gain	1.0000
2:42263177:GC:G	acceptor_gain	1.0000
2:42263177:GCA:G	acceptor_gain	1.0000
2:42263177:GCAT:G	acceptor_gain	1.0000
2:42263177:GCATA:G	acceptor_gain	1.0000

AlphaMissense

6455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:42295212:T:A	W436R	1.000
2:42295212:T:C	W436R	1.000
2:42304536:G:A	G651E	1.000
2:42315963:T:A	W657R	1.000
2:42315963:T:C	W657R	1.000
2:42317442:C:A	A691D	1.000
2:42317447:G:A	G693R	1.000
2:42317447:G:C	G693R	1.000
2:42317448:G:A	G693E	1.000
2:42317450:T:C	S694P	1.000
2:42325476:A:C	S722R	1.000
2:42325477:G:T	S722I	1.000
2:42325478:C:A	S722R	1.000
2:42325478:C:G	S722R	1.000
2:42325492:T:C	L727P	1.000
2:42325524:T:C	S738P	1.000
2:42325525:C:A	S738Y	1.000
2:42325525:C:T	S738F	1.000
2:42325529:C:A	N739K	1.000
2:42325529:C:G	N739K	1.000
2:42325530:T:C	S740P	1.000
2:42325531:C:G	S740W	1.000
2:42325533:G:A	G741R	1.000
2:42325533:G:C	G741R	1.000
2:42325534:G:A	G741E	1.000
2:42325534:G:T	G741V	1.000
2:42325536:G:C	D742H	1.000
2:42325537:A:T	D742V	1.000
2:42325543:A:T	E744V	1.000
2:42325554:T:A	W748R	1.000

dbSNP variants (sampled 300 via entrez): RS1000020817 (2:42189662 A>G), RS1000024185 (2:42251937 T>C), RS1000026688 (2:42213228 C>G), RS1000036958 (2:42199854 A>G), RS1000041877 (2:42232835 C>G,T), RS1000067109 (2:42181916 A>G,T), RS1000067577 (2:42294351 T>C), RS1000070075 (2:42307107 G>A,C), RS1000073840 (2:42279576 G>C), RS1000124951 (2:42186471 T>C), RS1000142260 (2:42180976 A>T), RS1000142462 (2:42314091 G>A), RS1000143670 (2:42278712 T>C), RS1000148520 (2:42270460 A>C), RS1000172117 (2:42238585 G>A,T)

Disease associations

OMIM: gene MIM:607442 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006481_14	Lung function (FEV1)	3.000000e-08
GCST006481_36	Lung function (FEV1)	8.000000e-08
GCST007692_113	Chronic obstructive pulmonary disease	5.000000e-08
GCST008833_23	Type 2 diabetes	3.000000e-08
GCST009391_1804	Metabolite levels	6.000000e-06
GCST010320_36	PR interval	2.000000e-08
GCST010321_188	PR interval	2.000000e-08
GCST90020028_25	Hip circumference adjusted for BMI	9.000000e-10
GCST90020028_26	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0010403	triacylglycerol 48:0 measurement
EFO:0004462	PR interval
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL1075114 (SINGLE PROTEIN), CHEMBL3883330 (CHIMERIC PROTEIN), CHEMBL4296166 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748232 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066842 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066862 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193829 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195606 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 55,423 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3353410	OSIMERTINIB	4	8,898
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL4298138	REPOTRECTINIB	4	1,038
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL3545360	ASP-3026	1	665

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

ChEMBL bioactivities

388 potent at pChembl≥5 of 388 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.77	IC50	0.17	nM	CHEMBL3687205
9.70	IC50	0.2	nM	LORLATINIB
9.68	IC50	0.21	nM	CHEMBL3687207
9.66	IC50	0.22	nM	CHEMBL3687206
9.64	IC50	0.23	nM	CHEMBL3889838
9.62	IC50	0.24	nM	CHEMBL3687201
9.59	IC50	0.26	nM	CHEMBL3687211
9.59	IC50	0.26	nM	CHEMBL3687204
9.59	IC50	0.26	nM	CHEMBL3687202
9.48	IC50	0.33	nM	CHEMBL3687198
9.47	IC50	0.34	nM	CHEMBL3687209
9.43	IC50	0.37	nM	CHEMBL3687193
9.31	IC50	0.49	nM	CHEMBL3687210
9.19	IC50	0.65	nM	CHEMBL3687200
9.15	IC50	0.7	nM	CHEMBL4286522
9.11	IC50	0.77	nM	CHEMBL3687197
9.03	IC50	0.93	nM	CHEMBL3687212
9.03	IC50	0.94	nM	CHEMBL4572977
9.00	IC50	1	nM	CHEMBL3687216
9.00	IC50	0.99	nM	CHEMBL3687189
8.91	IC50	1.22	nM	CHEMBL6162078
8.89	IC50	1.3	nM	LORLATINIB
8.85	IC50	1.4	nM	CHEMBL3687223
8.82	IC50	1.5	nM	GILTERITINIB
8.82	IC50	1.5	nM	CHEMBL3687215
8.80	IC50	1.6	nM	LORLATINIB
8.77	IC50	1.7	nM	CHEMBL3975354
8.75	IC50	1.79	nM	CERITINIB
8.72	IC50	1.9	nM	CHEMBL3687218
8.70	IC50	2	nM	CHEMBL3746665
8.70	IC50	2	nM	ALECTINIB
8.70	IC50	2	nM	CHEMBL3735401
8.70	IC50	2	nM	CHEMBL3746522
8.70	IC50	2	nM	CHEMBL3746960
8.70	IC50	2	nM	CHEMBL3747267
8.70	IC50	2	nM	CHEMBL3397300
8.68	IC50	2.1	nM	CHEMBL3687221
8.68	IC50	2.1	nM	CHEMBL3687195
8.68	IC50	2.09	nM	CHEMBL6151439
8.66	IC50	2.2	nM	CHEMBL3687225
8.64	IC50	2.3	nM	CHEMBL3687217
8.59	IC50	2.6	nM	CHEMBL4518930
8.55	IC50	2.8	nM	CHEMBL4582572
8.55	IC50	2.8	nM	CHEMBL3687194
8.52	IC50	3	nM	CHEMBL3397300
8.52	IC50	3	nM	ALECTINIB
8.52	IC50	3	nM	CHEMBL3746665
8.52	IC50	3	nM	CHEMBL3735401
8.51	IC50	3.1	nM	CHEMBL4530476
8.43	IC50	3.72	nM	CHEMBL6142200

PubChem BioAssay actives

290 with measured affinity, of 790 total; 44 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Lorlatinib	1419626: Inhibition of wild type EML4/ALK F1174L mutant (unknown origin) expressed in NIH/3T3 cells	ic50	0.0002	uM
(16R)-19-amino-13-fluoro-3,5,8,16-tetramethyl-17-oxa-4,8,20-triaza-5-azoniatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,10(15),11,13,18,20-octaen-9-one	1419625: Inhibition of wild type EML4/ALK (unknown origin) expressed in NIH/3T3 cells	ic50	0.0007	uM
2-[4-(3-cyano-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazol-8-yl)pyrazol-1-yl]-N,N-dimethylacetamide	1267028: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0020	uM
8-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267028: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0020	uM
2-[4-(3-cyano-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazol-8-yl)pyrazol-1-yl]-N,N,2-trimethylpropanamide	1267034: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0020	uM
8-[4-(dimethylamino)piperidin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267028: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0020	uM
Alectinib	1267028: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0020	uM
5-chloro-2-N-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl]-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine	1267035: Inhibition of EML4-ALK G1269A mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0020	uM
9-ethyl-6,6-dimethyl-8-(4-methylpiperazin-1-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267028: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0020	uM
Crizotinib	2161901: Inhibition of EML4-ALK (unknown origin) transformed in mouse BaF3 cells by HTRF assay	ic50	0.0050	uM
N-[5-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.0070	uM
8-[1-[3-(dimethylamino)propyl]pyrazol-4-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267029: Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0080	uM
N-[5-[[5-chloro-4-[2-(dimethylsulfamoyl)anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.0080	uM
Brigatinib	2183226: Inhibition of EML4-ALK G1269A mutant (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of ALK-driven cell growth incubated for 3 to 5 weeks	ic50	0.0090	uM
2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine	2161901: Inhibition of EML4-ALK (unknown origin) transformed in mouse BaF3 cells by HTRF assay	ic50	0.0100	uM
3-methyl-6-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-2H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	1711445: Inhibition EML4-ALK (unknown origin)	ic50	0.0100	uM
Repotrectinib	1579898: Inhibition of EML4/ALK phosphorylation (unknown origin)	ic50	0.0130	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1579879: Inhibition of EML4/ALK in human NCI-H2228 cells	ic50	0.0160	uM
Ceritinib	2183218: Inhibition of EML4-ALK V1180L mutant (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of ALK-driven cell growth incubated for 3 to 5 weeks	ic50	0.0160	uM
9-ethyl-6,6-dimethyl-8-[1-(oxan-4-yl)pyrazol-4-yl]-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267034: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0200	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[5-fluoro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.0200	uM
9-ethyl-6,6-dimethyl-8-(1-methylpyrazol-4-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267034: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0210	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[4-[2-(dimethylsulfamoyl)anilino]-5-iodopyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.0210	uM
9-ethyl-6,6-dimethyl-11-oxo-8-(1H-pyrazol-4-yl)-5H-benzo[b]carbazole-3-carbonitrile	1267034: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0220	uM
9-ethyl-6,6-dimethyl-11-oxo-8-(1-piperidin-4-ylpyrazol-4-yl)-5H-benzo[b]carbazole-3-carbonitrile	1267029: Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0240	uM
4-(3-cyano-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazol-8-yl)-N,N-dimethylpyrazole-1-carboxamide	1267034: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0250	uM
8-[4-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetyl]piperazin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1847262: Protac activity at CRBN/EML4-ALK in human NCI-H3122 cells assessed as induction of EML4-ALK fusion protein degradation incubated for 16 hrs by Western blot analysis	ec50	0.0274	uM
Entrectinib	1300441: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay	ic50	0.0280	uM
9-ethyl-6,6-dimethyl-11-oxo-8-(1H-pyrazol-5-yl)-5H-benzo[b]carbazole-3-carbonitrile	1267034: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0320	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[4-[2-(dimethylsulfamoyl)anilino]-5-fluoropyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.0390	uM
9-ethyl-6,6-dimethyl-8-(1,2-oxazol-4-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267028: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0590	uM
9-ethyl-6,6-dimethyl-11-oxo-8-(2H-triazol-4-yl)-5H-benzo[b]carbazole-3-carbonitrile	1267034: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay	ic50	0.0800	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[5-iodo-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.0870	uM
N-[1-[4-[[5-chloro-4-(2-dimethylphosphorylanilino)pyrimidin-2-yl]amino]-3-methoxyphenyl]piperidin-4-yl]-N’-[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]undecanediamide	1691168: Inhibition of EML4-ALK G1202R mutant fusion protein (unknown origin) expressed in HEK293T cells	ic50	0.1464	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[4-[2-(dimethylsulfamoyl)anilino]pyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.2170	uM
N-[1-[4-[[5-chloro-4-(2-dimethylphosphorylanilino)pyrimidin-2-yl]amino]-3-methoxyphenyl]piperidin-4-yl]-N’-[(2S)-1-[(2S,4S)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]undecanediamide	1691166: Protac activity at VHL/EML4-ALK G1202R mutant fusion protein (unknown origin) expressed in HEK293T cells assessed as inhibition of cell growth	ic50	0.6080	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149859: Binding affinity to human EML4 incubated for 45 mins by Kinobead based pull down assay	kd	0.7607	uM
N-[5-[[5-chloro-4-(2-dimethylphosphorylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	0.9610	uM
Osimertinib	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	1.7480	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	2.1820	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[4-(2-dimethylphosphorylanilino)-5-iodopyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	2.3570	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[4-(2-dimethylphosphorylanilino)-5-fluoropyrimidin-2-yl]amino]-4-methoxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	2.5060	uM
N-[2-[2-[[2-[4-[6-[(6-acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]-3-pyridinyl]piperazin-1-yl]acetyl]amino]ethyldisulfanyl]ethyl]-8-[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-methyl-5-propan-2-yloxyphenyl]piperidin-1-yl]-N-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethylamino]-2-oxoethyl]-8-oxooctanamide	1969146: PROTAC activity at CRBN/EML4-ALK in human NCI-H3122 cells assessed as reduction in EML4-ALK fusion protein level incubated for 24 hrs by Western blot analysis	ec50	2.8300	uM
N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide	1583842: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay	ec50	6.2580	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, decreases methylation, increases stability	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
bisphenol A	affects cotreatment, decreases expression, increases expression	2
Crizotinib	decreases stability, increases mutagenesis, decreases response to substance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
lead acetate	affects cotreatment, increases expression	1
titanium dioxide	increases methylation	1
beta-lapachone	decreases expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
alpha-cobratoxin	decreases expression, decreases reaction	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric chloride	decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

304 unique, capped per target: 304 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652901	Binding	Binding affinity to human EML4 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

44 cell lines: 35 cancer cell line, 9 factor-dependent cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1543	NCI-H2228	Cancer cell line	Female
CVCL_4V13	NCI-H2228-Luc	Cancer cell line	Female
CVCL_4Y37	NCI-H3122-CHR-A1	Cancer cell line	Male
CVCL_5051	SNU-324	Cancer cell line	Male
CVCL_5160	NCI-H3122	Cancer cell line	Male
CVCL_A1EF	ABC-14	Cancer cell line	Male
CVCL_A1EG	ABC-17	Cancer cell line	Male
CVCL_A763	DFCI032	Cancer cell line	Female
CVCL_AY53	NCI-H3122-CR1	Cancer cell line	Male
CVCL_B1R6	Abcam HeLa EML4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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