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): 197 total — 1 pathogenic
• GTEx eGene: eQTL in 34 tissues, sQTL in 31 (q < 0.05)
• Drug target: yes — 5 via a complex or family; 10 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 4 — Alectinib Hydrochloride, Ceritinib, Crizotinib, +1 more (EML4-ALK)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.68 (unconstrained)
• MANE Select transcript: NM_019063
• Notable: 197 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 34 — 20 protein_coding, 9 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000318522

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 1, TSL 3: 1, TSL 4: 1, TSL 5: 1

ENST00000318522, ENST00000401738, ENST00000402711, ENST00000406175, ENST00000409040, ENST00000472632, ENST00000480320, ENST00000482660, ENST00000862356, ENST00000862357, ENST00000921467, ENST00000921468, ENST00000921469, ENST00000921470, ENST00000921471, ENST00000921472, ENST00000921473, ENST00000921474, ENST00000921475, ENST00000963712, ENST00000963713, ENST00000985380, ENST00000985381, ENST00000985382, ENST00001037254, ENST00001037256, ENST00001075709, ENST00001075710, ENST00001075711, ENST00001109603, ENST00001109604, ENST00001127314, ENST00001127315, ENST00001144577

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.

Highest expression (Bgee): tibia, jejunal mucosa, visceral pleura, tonsil, mucosa of sigmoid colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EML4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 34 tissues and its splicing (sQTL) in 31 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 65 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	6.2e-100	+0.92	2:42128807:C:A
Thyroid	sqtl	1.7e-42	-0.94	2:42288530:A:C
Nerve Tibial	eqtl	9.5e-35	-0.28	2:42378700:T:C
Thyroid	eqtl	8.1e-32	-0.28	2:42351009:A:G
Pancreas	eqtl	4.8e-28	-1.07	2:42188097:C:T
Skin Sun Exposed Lower leg	sqtl	9.6e-27	-0.56	2:42272689:T:A
Lung	sqtl	2.6e-25	-0.42	2:42287509:C:T
Adipose Subcutaneous	eqtl	1.2e-23	+0.27	2:42463933:C:T
Skin Sun Exposed Lower leg	eqtl	5.1e-19	+0.21	2:42133968:A:G
Whole Blood	eqtl	5.4e-18	-0.14	2:42102571:C:G
Skin Not Sun Exposed Suprapubic	sqtl	1.2e-17	-0.50	2:42318200:C:T
Whole Blood	sqtl	1.2e-16	-0.48	2:42328882:A:T
Skin Not Sun Exposed Suprapubic	eqtl	3.6e-16	+0.24	2:42133968:A:G
Adipose Visceral Omentum	sqtl	4.1e-15	-0.50	2:42318200:C:T
Artery Tibial	eqtl	5.0e-15	-0.24	2:42294557:A:G
Adipose Subcutaneous	sqtl	5.0e-14	-0.50	2:42273109:G:A
Artery Tibial	sqtl	1.7e-13	+0.45	2:42272689:T:A
Nerve Tibial	sqtl	4.4e-13	+0.45	2:42318879:A:T
Heart Atrial Appendage	eqtl	3.8e-12	+0.19	2:42170358:T:C
Cells EBV-transformed lymphocytes	sqtl	6.1e-11	-0.86	2:42304731:G:T

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

showing 100 of 284 tissues 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
caecum	UBERON:0001153	90.88	gold quality
pancreas	UBERON:0001264	90.73	gold quality
placenta	UBERON:0001987	90.72	gold quality
gingiva	UBERON:0001828	90.70	gold quality
colonic epithelium	UBERON:0000397	90.67	gold quality
caput epididymis	UBERON:0004358	90.66	gold quality
ileal mucosa	UBERON:0000331	90.46	gold quality
liver	UBERON:0002107	90.38	gold quality
skin of hip	UBERON:0001554	90.34	gold quality
superficial temporal artery	UBERON:0001614	90.27	gold quality
skin of abdomen	UBERON:0001416	90.24	gold quality
skin of leg	UBERON:0001511	90.23	gold quality
upper lobe of left lung	UBERON:0008952	90.07	gold quality
blood	UBERON:0000178	90.04	gold quality
esophagus squamous epithelium	UBERON:0006920	89.95	gold quality
trabecular bone tissue	UBERON:0002483	89.85	gold quality
vermiform appendix	UBERON:0001154	89.80	gold quality
adrenal cortex	UBERON:0001235	89.78	gold quality
upper lobe of lung	UBERON:0008948	89.76	gold quality
zone of skin	UBERON:0000014	89.64	gold quality
left adrenal gland cortex	UBERON:0035825	89.62	gold quality
adrenal gland	UBERON:0002369	89.60	gold quality
granulocyte	CL:0000094	89.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.41	gold quality
right adrenal gland cortex	UBERON:0035827	89.36	gold quality
left adrenal gland	UBERON:0001234	89.32	gold quality
nipple	UBERON:0002030	89.25	gold quality
corpus epididymis	UBERON:0004359	89.23	gold quality
intestine	UBERON:0000160	89.21	gold quality
right coronary artery	UBERON:0001625	89.12	gold quality
penis	UBERON:0000989	89.08	gold quality
nasal cavity mucosa	UBERON:0001826	88.99	gold quality
transverse colon	UBERON:0001157	88.90	gold quality
right adrenal gland	UBERON:0001233	88.77	gold quality
islet of Langerhans	UBERON:0000006	88.71	gold quality
jejunum	UBERON:0002115	88.66	gold quality
bronchial epithelial cell	CL:0002328	88.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.49	gold quality
saliva-secreting gland	UBERON:0001044	88.49	gold quality
bone marrow cell	CL:0002092	88.42	gold quality
cartilage tissue	UBERON:0002418	88.39	gold quality
stomach	UBERON:0000945	88.32	gold quality
cortical plate	UBERON:0005343	88.28	gold quality
large intestine	UBERON:0000059	88.21	gold quality
mucosa of transverse colon	UBERON:0004991	88.21	gold quality
fundus of stomach	UBERON:0001160	88.06	gold quality
colon	UBERON:0001155	87.97	gold quality
right lung	UBERON:0002167	87.95	gold quality
thyroid gland	UBERON:0002046	87.92	gold quality
left lobe of thyroid gland	UBERON:0001120	87.83	gold quality
urethra	UBERON:0000057	87.74	gold quality
body of stomach	UBERON:0001161	87.72	gold quality
coronary artery	UBERON:0001621	87.71	gold quality
left coronary artery	UBERON:0001626	87.71	gold quality
leukocyte	CL:0000738	87.63	gold quality
minor salivary gland	UBERON:0001830	87.59	gold quality
sural nerve	UBERON:0015488	87.53	gold quality
right lobe of thyroid gland	UBERON:0001119	87.47	gold quality
monocyte	CL:0000576	87.40	gold quality
palpebral conjunctiva	UBERON:0001812	87.38	gold quality
mononuclear cell	CL:0000842	87.35	gold quality
mouth mucosa	UBERON:0003729	87.33	gold quality
urinary bladder	UBERON:0001255	87.32	gold quality
metanephros cortex	UBERON:0010533	87.24	gold quality
lung	UBERON:0002048	87.18	gold quality
renal medulla	UBERON:0000362	87.01	gold quality
stromal cell of endometrium	CL:0002255	86.98	gold quality
testis	UBERON:0000473	86.86	gold quality
ovary	UBERON:0000992	86.79	gold quality
embryo	UBERON:0000922	86.72	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	38.9	not detected
Duodenum	tissue	36.5	high
Liver	tissue	35.7	high
Small intestine	tissue	34.4	high
Placenta	tissue	33.5	high
Appendix	tissue	30.6	high
Tonsil	tissue	28.1	high
Spleen	tissue	26.7	high
Lymph node	tissue	26.4	high
Urinary bladder	tissue	25.5	high
Pancreas	tissue	22.9	high
Lung	tissue	22.9	high
Rectum	tissue	22.3	high
Colon	tissue	22.1	high
Spinal cord	tissue	20.5
Thyroid gland	tissue	20.2	high
Salivary gland	tissue	19.8	high
Stomach 1	tissue	19.7	high
Superior colliculi	tissue	19.6
Testis	tissue	19.1	high
Gallbladder	tissue	18.7	high
Kidney	tissue	18.1	high
Septum	tissue	17.7
Skin 1	tissue	17.3	medium
Hypothalamus	tissue	17.3
Choroid plexus	tissue	17.0
Putamen	tissue	16.9
Amygdala	tissue	16.8
Substantia nigra	tissue	16.4
Hippocampal formation	tissue	16.4
Ventral forebrain	tissue	16.4
Entorhinal cortex	tissue	16.2
Olfactory bulb	tissue	16.1
Basal ganglia	tissue	15.8	medium
Cerebral cortex	tissue	15.7	medium
Cerebellum	tissue	15.7	high
Temporal cortex	tissue	15.7
Midbrain	tissue	15.4
Pons	tissue	15.3
Medulla oblongata	tissue	15.0
Thalamus	tissue	14.9
Motor cortex	tissue	14.6
Occipital cortex	tissue	14.6
Retrosplenial and cingulate cortex	tissue	14.5
Periaqueductal gray	tissue	14.4
Retrosplenial cortex	tissue	14.3
Insular cortex	tissue	14.2
Prefrontal cortex	tissue	14.0
Thymus	tissue	13.9
Somatosensory cortex	tissue	13.7
Smooth muscle	tissue	13.2	not detected
Breast	tissue	13.1	medium
Parathyroid gland	tissue	12.9	medium
Adrenal gland	tissue	12.9	high
Corpus callosum	tissue	12.4
Nucleus accumbens	tissue	11.1
Cervix	tissue	11.0	high
Hippocampus	tissue	10.8	high
Ovary	tissue	10.7	medium
Frontal cortex	tissue	10.6

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal spinal cord (20.5), Ventral spinal cord (17.1), Anterior thalamic nucleus, ventral (17.0), Subiculum (16.4), Ventral hippocampus (15.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting EML4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 137 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.84e-07, LOEUF 0.68, missense Z -1.33 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000318522 — one region, missense o/e 1.14.

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		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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1926048) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vocalization	1
abnormal coat/hair pigmentation	1
prolonged PR interval	1
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	Q2TAF3	93.6%	Diamond
Xenopus tropicalis	Q6DIP5	93.6%	Diamond
Strongylocentrotus purpuratus	Q26613	90.8%	Diamond
Lytechinus variegatus	Q9Y1C1	90.8%	Diamond
Dictyostelium discoideum	Q86HX1	46.2%	Diamond
Drosophila melanogaster	Q9VUI3	38.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KCNG3	protein-coding	170850
PKDCC	protein-coding	91461
COX7A2L	protein-coding	9167
EML4-AS1	ncRNA	102723824
LINC02898	ncRNA	400950
MTA3	protein-coding	57504

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): B5MBZ0, Q9HC35

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 by resolution:

PDB	Title	Method	Resolution (Å)
4CGC	Crystal structure of the trimerization domain of human EML4	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): annulus; microtubules; primary cilium; calyx; cytokinetic bridge; cytosol; perinuclear theca; principal piece

Antibody reliability (HPA): IH enhanced · IF supported

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)

Position	Role
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)

Type	Positions
N-acetylmethionine	1
Phosphoserine	7, 13, 16, 61, 134, 144, 146, 171, 200, 891, 895, 903, 978, 981
Phosphothreonine	96, 201, 237, 490, 609, 897, 899
Phosphotyrosine	226

Mutagenesis-validated functional residues (4)

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

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 10; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

10 pathways:

ID	Pathway	Evidence
R-HSA-9700645	ALK mutants bind TKIs ⚕	curated
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-68886	M Phase	—
R-HSA-68877	Mitotic Prometaphase	—

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 (11): cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), midbody (GO:0030496), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Signaling by ALK in cancer	2
Mitotic Prometaphase	1
Disease	1
M Phase	1
Cell Cycle, Mitotic	1
Cell Cycle	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

21 GO namespaces:

Category	Terms
cellular anatomical structure	6
tubulin binding	3
microtubule cytoskeleton	3
cellular process	2
metaphase chromosome alignment	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
cytoskeleton	1
spindle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
attachment of spindle microtubules to kinetochore	BP	mutant phenotype
mitotic metaphase chromosome alignment	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
intercellular bridge	CC	direct assay
membrane	CC	high-throughput assay
microtubule	CC	direct assay
microtubule cytoskeleton	CC	direct assay
microtubule organizing center	CC	direct assay
midbody	CC	direct assay
mitotic spindle	CC	direct assay
alpha-tubulin binding	MF	direct assay
beta-tubulin binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,676 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EML4	ALK	Q9UM73	974
EML4	EGFR	P00533	881
EML4	ROS1	P08922	861
EML4	KIF5B	P33176	781
EML4	KRAS	P01116	760
EML4	NPM1	P06748	753
EML4	RET	P07949	741
EML4	BRAF	P15056	719
EML4	RET	P07949	702
EML4	STRN	O43815	700
EML4	TPM3	P06753	675
EML4	NKX2-1	P43699	660
EML4	KLC1	Q07866	657
EML4	ERBB2	P04626	654
EML4	STK11	Q15831	627

IntAct

Human interaction partners of EML4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
ARIH2	physical association	0.000	1
ARL4D	physical association	0.000	1
NEK6	physical association	0.000	1
NEK7	physical association	0.000	1

BioGRID (185 interactions; top human partners by supporting records): TUBA1B (Co-localization; 4 records), NEK9 (Affinity Capture-Western; 3 records), TUBB (Affinity Capture-MS; 3 records), TUBB2A (Affinity Capture-MS; 3 records), TUBB2B (Affinity Capture-MS; 3 records), ATG16L1 (Affinity Capture-MS; 2 records), BAG2 (Affinity Capture-MS; 2 records), CTAGE5 (Affinity Capture-MS; 2 records), DCTN1 (Proximity Label-MS; 2 records), EML1 (Affinity Capture-MS; 2 records), FBXO28 (Affinity Capture-MS; 2 records), NEK6 (Affinity Capture-MS; 2 records), NEK7 (Affinity Capture-MS; 2 records), NUDC (Affinity Capture-Western; 2 records), PRPS1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

4 signaling 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

Disease & clinical

Genetic variants

Variant evidence for EML4: 197 ClinVar records (1 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	153
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4851086	GRCh37/hg19 2p21(chr2:41998400-42410029)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore EML4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 2,965):

Position(s)	Effect	Δscore	Sites
2:42245497	acceptor_gain	1.0000
2:42245502–42245504	acceptor_gain	1.0000	4
2:42245503	acceptor_loss	1.0000
2:42245688–42245689	donor_loss	1.0000	5
2:42263307–42263308	donor_loss	1.0000	3
2:42264732–42264733	donor_loss	1.0000	5
2:42280848–42280849	acceptor_loss	1.0000	6
2:42288225–42288226	acceptor_loss	1.0000	6
2:42295122	acceptor_gain	1.0000
2:42295260–42295261	donor_loss	1.0000	4

AlphaMissense

2,338 missense substitutions predicted likely pathogenic (of 6,455 scored), across 554 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M238	9	0.883	0.997
D809	8	0.999	1.000
D742	8	0.998	1.000
H720	8	0.997	0.999
S722	8	0.997	1.000
D791	8	0.997	0.999
D808	8	0.996	1.000
H726	8	0.995	0.999
D788	8	0.995	0.999
H833	8	0.995	0.999
D728	8	0.994	0.999
H695	8	0.993	0.999
D613	8	0.992	0.999
H836	8	0.992	0.998
D856	8	0.989	0.998
D696	8	0.986	0.999
N793	8	0.979	0.999
D384	8	0.968	0.995
H308	8	0.967	0.989
F810	8	0.967	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.2e-07
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.00087

Disease associations

OMIM: gene MIM:607442 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST90020028_933	Hip circumference adjusted for BMI	9e-10
GCST90020028_809	Hip circumference adjusted for BMI	1e-8
GCST010320_111	PR interval	2e-8
GCST010321_73	PR interval	2e-8
GCST006481_15	Lung function (FEV1)	3e-8
GCST008833_23	Type 2 diabetes	3e-8
GCST007692_40	Chronic obstructive pulmonary disease	5e-8
GCST006481_36	Lung function (FEV1)	8e-8
GCST009391_1229	Metabolite levels	6e-6

EFO canonical traits (from GWAS)

4 canonical traits:

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)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes EML4 — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ALECTINIB HYDROCHLORIDE	EML4-ALK	2	4
CERITINIB	EML4-ALK	2	4
CRIZOTINIB	EML4-ALK	2	4
LORLATINIB	EML4-ALK	2	4
PLB1003	EML4-ALK	2	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 58,605 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

10 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1738797	ALECTINIB	4	7,111
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL3286830	LORLATINIB	4	3,833
CHEMBL3353410	OSIMERTINIB	4	9,448
CHEMBL4298138	REPOTRECTINIB	4	1,100
CHEMBL3545360	ASP-3026	1	711

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

61 measured of 64 human assays (65 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
AP26113	IC50	0.07 nM
CHEMBL4286522	KI	0.29 nM
AP-26113	IC50	0.37 nM
Alectinib	IC50	0.59 nM	US-9126931: Tetracyclic compound
5-bromo-4-N-(2-dimethylphosphoryl-4-methylphenyl)-2-N-[2-methoxy-5-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	IC50	0.77 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-5-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	IC50	0.86 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
CHEMBL3736273	IC50	0.9 nM
9-ethyl-6,6-dimethyl-8-(4-methylpiperazin-1-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	2 nM	US-11066363: Substituted 6,11-dihydro-5H-benzo[B]carbazoles as inhibitors of ALK and SRPK
8-[4-(dimethylamino)piperidin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	2 nM	US-11066363: Substituted 6,11-dihydro-5H-benzo[B]carbazoles as inhibitors of ALK and SRPK
8-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	2 nM	US-11066363: Substituted 6,11-dihydro-5H-benzo[B]carbazoles as inhibitors of ALK and SRPK
CHEMBL6151439	IC50	2.1 nM
CHEMBL6142200	IC50	3.7 nM
CHEMBL6144893	IC50	4.5 nM
CHEMBL6143935	IC50	4.7 nM
CERITINIB	IC50	5 nM	US-10053458: Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient
Lorlatinib	IC50	5.5 nM	US-11517561: Macrocycle and composition comprising thereof
CHEMBL6133955	IC50	5.5 nM
CHEMBL6143027	IC50	5.6 nM
CHEMBL3747267	IC50	6 nM
CHEMBL6091887	IC50	6.8 nM
CHEMBL6149199	IC50	7.3 nM
CHEMBL6144949	IC50	7.4 nM
CHEMBL6102777	IC50	8.8 nM
ASP-3026	IC50	10 nM
CHEMBL6103055	IC50	10 nM
CHEMBL3734844	IC50	11 nM
5-bromo-2-N-[5-chloro-2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-dimethylphosphoryl-4-methylphenyl)pyrimidine-2,4-diamine	IC50	12.9 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
5-bromo-2-N-[5-bromo-2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-dimethylphosphoryl-4-methylphenyl)pyrimidine-2,4-diamine	IC50	13.7 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
CHEMBL3746678	IC50	14 nM
5-bromo-2-N-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxy-5-methylphenyl]-4-N-(2-dimethylphosphoryl-4-methylphenyl)pyrimidine-2,4-diamine	IC50	14.6 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
5-chloro-4-N-(2-dimethylphosphoryl-4-methylphenyl)-2-N-[2-methoxy-5-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	IC50	14.9 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
CHEMBL4565984	IC50	15 nM
5-chloro-2-N-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxy-5-methylphenyl]-4-N-(2-dimethylphosphoryl-4-methylphenyl)pyrimidine-2,4-diamine	IC50	16.3 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
CHEMBL3735401	IC50	17 nM
CHEMBL4448107	IC50	17 nM
CHEMBL4449391	IC50	17 nM
CHEMBL4473365	IC50	18 nM
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	IC50	20 nM	US-8592432: Compounds and compositions as protein kinase inhibitors
9-ethyl-6,6-dimethyl-8-(1-methylpyrazol-4-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	21 nM	US-11066363: Substituted 6,11-dihydro-5H-benzo[B]carbazoles as inhibitors of ALK and SRPK
5-bromo-4-N-(2-dimethylphosphoryl-4-methylphenyl)-2-N-[5-ethyl-2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	IC50	21.3 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
CHEMBL4540442	IC50	31 nM
5-bromo-4-N-(2-dimethylphosphoryl-4-fluorophenyl)-2-N-[2-methoxy-5-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	IC50	31.2 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
CHEMBL4467561	IC50	38 nM
Repotrectinib	IC50	39 nM	US-12129258: Diaryl macrocyclic compound and pharmaceutical composition, and use thereof
CHEMBL4520341	IC50	40 nM
CHEMBL4581316	IC50	41 nM
9-ethyl-6,6-dimethyl-11-oxo-8-(1H-pyrazol-5-yl)-5H-benzo[b]carbazole-3-carbonitrile	IC50	50 nM	US-11066363: Substituted 6,11-dihydro-5H-benzo[B]carbazoles as inhibitors of ALK and SRPK
4-(3-cyano-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazol-8-yl)-N,N-dimethylpyrazole-1-carboxamide	IC50	56 nM	US-11066363: Substituted 6,11-dihydro-5H-benzo[B]carbazoles as inhibitors of ALK and SRPK
9-ethyl-6,6-dimethyl-8-(1,2-oxazol-4-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	59 nM	US-11066363: Substituted 6,11-dihydro-5H-benzo[B]carbazoles as inhibitors of ALK and SRPK
CHEMBL3746482	IC50	64 nM

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

303 with measured affinity, of 839 total; 50 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
5-bromo-4-N-(2-dimethylphosphoryl-4-methylphenyl)-2-N-[2-methoxy-5-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	2242669: Inhibition of N-terminal GST-fused human EML4-ALK (1 to 1059 residues) extracted from baculovirus expression system using Srctide as substrate incubated for 1 to 5 hrs in presence of ATP/Mg by Mobility shift assay	ic50	0.0012	uM
Ceritinib	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0018	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
N-[5-[[5-chloro-4-[3-fluoro-2-(1,1,1,2,3,3,3-heptadeuteriopropan-2-ylsulfinyl)anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0021	uM
N-[5-[[5-chloro-4-[2-(1,1,2,2,2-pentadeuterioethylsulfinyl)anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0037	uM
N-[5-[[5-chloro-4-(2-ethylsulfinyl-3-fluoroanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0045	uM
N-[5-[[5-chloro-4-(2-ethylsulfinylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0047	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-(3-fluoro-2-propan-2-ylsulfinylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0055	uM
N-[5-[[5-chloro-4-[3-fluoro-2-(1,1,2,2,2-pentadeuterioethylsulfinyl)anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0056	uM
N-[5-[[5-chloro-4-(4-chloro-2-propan-2-ylsulfinylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0068	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
N-[5-[[5-chloro-4-(3-chloro-2-ethylsulfinylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0073	uM
N-[5-[[5-chloro-4-(3-chloro-2-propan-2-ylsulfinylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0074	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
N-[5-[[5-chloro-4-[4-chloro-2-(1,1,2,2,2-pentadeuterioethylsulfinyl)anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0088	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
N-[5-[[5-chloro-4-[2-(1,1,1,2,3,3,3-heptadeuteriopropan-2-ylsulfinyl)anilino]pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	2212115: Inhibition of EML4-ALK (unknown origin) phosphorylation by ELISA	ic50	0.0100	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
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

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	increases expression, affects cotreatment, decreases 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)	decreases expression, affects cotreatment	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	increases reaction, affects binding	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

47 cell lines: 38 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for EML4 across ~30M SureChEMBL compounds — explore on Sugi Predict.