SMYD5

Summary

SMYD5 (SMYD family member 5, HGNC:16258) is a protein-coding gene on chromosome 2p13.2, encoding Protein-lysine N-trimethyltransferase SMYD5 (Q6GMV2). Protein-lysine N-trimethyltransferase that specifically catalyzes trimethylation of ‘Lys-22’ of the RPL40/eL40 subunit of the 60S ribosome, thereby promoting translation elongation and protein synthesis.

Enables protein-lysine N-methyltransferase activity. Involved in positive regulation of cytoplasmic translational elongation; regulation of stem cell differentiation; and transposable element silencing by heterochromatin formation. Is active in cytoplasm.

Source: NCBI Gene 10322 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 68 total
• Druggable target: yes
• MANE Select transcript: NM_006062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16258
Approved symbol	SMYD5
Name	SMYD family member 5
Location	2p13.2
Locus type	gene with protein product
Status	Approved
Aliases	RRG1, NN8-4AG, ZMYND23
Ensembl gene	ENSG00000135632
Ensembl biotype	protein_coding
OMIM	619114
Entrez	10322

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000258100, ENST00000389501, ENST00000413491, ENST00000443900, ENST00000474652, ENST00000477038, ENST00000486518, ENST00000491204, ENST00000629411, ENST00000899922, ENST00000899923, ENST00000927772, ENST00000927773, ENST00000967252, ENST00000967253

RefSeq mRNA: 1 — MANE Select: NM_006062 NM_006062

CCDS: CCDS33221

Canonical transcript exons

ENST00000389501 — 13 exons

Exon	Start	End
ENSE00000920786	73223426	73223532
ENSE00000920787	73223947	73224003
ENSE00000920788	73224866	73224960
ENSE00000920789	73225631	73225701
ENSE00001302944	73225796	73227221
ENSE00001698488	73220051	73220190
ENSE00003460713	73220661	73220782
ENSE00003489415	73218861	73218969
ENSE00003520582	73223036	73223106
ENSE00003552520	73222755	73222817
ENSE00003579624	73221826	73221930
ENSE00003581712	73221165	73221234
ENSE00003848248	73214245	73214362

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 90.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0440 / max 97.9314, expressed in 1764 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20942	14.0440	1764

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	90.65	gold quality
right uterine tube	UBERON:0001302	90.64	gold quality
left ovary	UBERON:0002119	90.59	gold quality
apex of heart	UBERON:0002098	90.05	gold quality
right frontal lobe	UBERON:0002810	90.01	gold quality
right ovary	UBERON:0002118	89.78	gold quality
body of pancreas	UBERON:0001150	88.88	gold quality
endocervix	UBERON:0000458	88.80	gold quality
tibial nerve	UBERON:0001323	88.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.69	gold quality
body of uterus	UBERON:0009853	88.66	gold quality
left uterine tube	UBERON:0001303	88.62	gold quality
nucleus accumbens	UBERON:0001882	88.44	gold quality
right adrenal gland	UBERON:0001233	88.37	gold quality
cingulate cortex	UBERON:0003027	88.35	gold quality
anterior cingulate cortex	UBERON:0009835	88.25	gold quality
cerebellar hemisphere	UBERON:0002245	88.24	gold quality
cerebellar cortex	UBERON:0002129	88.06	gold quality
left adrenal gland	UBERON:0001234	88.03	gold quality
right adrenal gland cortex	UBERON:0035827	87.99	gold quality
left adrenal gland cortex	UBERON:0035825	87.97	gold quality
right lobe of thyroid gland	UBERON:0001119	87.76	gold quality
metanephros cortex	UBERON:0010533	87.71	gold quality
prefrontal cortex	UBERON:0000451	87.38	gold quality
right coronary artery	UBERON:0001625	87.26	gold quality
adenohypophysis	UBERON:0002196	87.24	gold quality
caudate nucleus	UBERON:0001873	87.19	gold quality
ectocervix	UBERON:0012249	87.19	gold quality
right testis	UBERON:0004534	87.17	gold quality
left testis	UBERON:0004533	87.11	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	134.94
E-GEOD-100618	no	40.34
E-ANND-3	no	3.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RARA

miRNA regulators (miRDB)

84 targeting SMYD5, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-762	99.58	66.61	1994

Literature-anchored findings (GeneRIF, showing 6)

• depletion of SMYD5 in human colon and lung cancer cells results in increased tumor growth and upregulation of genes overexpressed in colon and lung cancers, respectively. The findings implicate an important role for SMYD5 in maintaining chromosome integrity by regulating heterochromatin and repressing endogenous repetitive DNA elements during differentiation. (PMID:28951459)
• Sperm chromatin-condensing protamine enhances SMYD5 thermal stability. (PMID:33676231)
• The lysine methyltransferase SMYD5 amplifies HIV-1 transcription and is post-transcriptionally upregulated by Tat and USP11. (PMID:36897778)
• Negative regulation of SH2B3 by SMYD5 controls epithelial-mesenchymal transition in lung cancer. (PMID:38723947)
• SMYD5 methylation of rpL40 links ribosomal output to gastric cancer. (PMID:39048817)
• SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma. (PMID:39103523)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smyd5	ENSDARG00000071669
mus_musculus	Smyd5	ENSMUSG00000033706
rattus_norvegicus	Smyd5	ENSRNOG00000015589
drosophila_melanogaster	SmydA-7	FBGN0034182
drosophila_melanogaster	Smyd5	FBGN0038869

Paralogs (5): SMYD1 (ENSG00000115593), ZMYND15 (ENSG00000141497), SMYD2 (ENSG00000143499), SMYD3 (ENSG00000185420), SMYD4 (ENSG00000186532)

Protein

Protein identifiers

Protein-lysine N-trimethyltransferase SMYD5 — Q6GMV2 (reviewed: Q6GMV2)

Alternative names: Protein NN8-4AG, Retinoic acid-induced protein 15, SET and MYND domain-containing protein 5, [histone H3]-lysine20 N-trimethyltransferase SMYD5, [histone H4]-lysine36 N-trimethyltransferase SMYD5

All UniProt accessions (4): C9IYN9, E2QRN5, Q6GMV2, F8WEJ9

UniProt curated annotations — full annotation on UniProt →

Function. Protein-lysine N-trimethyltransferase that specifically catalyzes trimethylation of ‘Lys-22’ of the RPL40/eL40 subunit of the 60S ribosome, thereby promoting translation elongation and protein synthesis. May also act as a histone methyltransferase in the context of histone octamers, but not on nucleosome substrates: trimethylates ‘Lys-36’ of histone H3 and ‘Lys-20’ of histone H4 to form H3K36me3 and H4K20me3, respectively. The histone methyltransferase activity, which is independent of its SET domain, is however unsure in vivo. In association with the NCoR corepressor complex, involved in the repression of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages, possibly by catalyzing the formation of H4K20me3 at the gene promoters. Plays an important role in embryonic stem (ES) cell self-renewal and differentiation. Maintains genome stability of ES cells during differentiation through regulation of heterochromatin formation and repression of endogenous repetitive DNA elements by promoting H4K20me3 marks. Acts as a regulator of the hypothermia response: its degradation in response to mild hypothermia relieves the formation of H3K36me3 at gene promoters, allowing expression of the neuroprotective gene SP1.

Subunit / interactions. Interacts with the N-CoR complex. Interacts with EHMT2 and CBX5.

Subcellular location. Cytoplasm.

Post-translational modifications. Ubiquitinated and degradaed by the proteasome in response to mild hypothermia (32 degrees Celsius), relieving repression of the SP1 gene.

Induction. Strongly up-regulated in gastric adenocarcinomas and hepatocellular carcinomas, driving malignant progression.

Miscellaneous. Acts as a strong promoter of malignant progression of gastric adenocarcinoma and hepatocellular carcinoma via its ability to mediate trimethylation of ‘Lys-22’ of the RPL40/eL40 subunit of the 60S ribosome and increase protein synthesis. SMYD5 inhibition significantly decreases cancer progression, and renders cancer cells hypersensitive to inhibitors of PI3K and mTOR.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily.

RefSeq proteins (1): NP_006053* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR044422	SMYD5_SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily

Pfam: PF00856

Catalyzed reactions (Rhea), 3 shown:

• L-lysyl-[protein] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:54192)
• L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:60324)
• L-lysyl(20)-[histone H4] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(20)-[histone H4] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:64456)

UniProt features (8 total): sequence conflict 2, chain 1, domain 1, zinc finger region 1, region of interest 1, binding site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2BQZ	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6GMV2-F1	88.88	0.74

Functional residue map

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

Ligand- & substrate-binding residues (1): 351

Mutagenesis-validated functional residues (1):

Position	Phenotype
351	abolished trimethylation of ’lys-22’ of the rpl40/el40 subunit of the 60s ribosome.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 192 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, RNGTGGGC_UNKNOWN, MORF_MSH3, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_TRANSLATIONAL_ELONGATION, YY1_Q6, GGCNKCCATNK_UNKNOWN, MODULE_503, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, COUP_01, GOBP_TRANSLATION

GO Biological Process (7): methylation (GO:0032259), negative regulation of gene expression, epigenetic (GO:0045814), transposable element silencing by heterochromatin formation (GO:0141005), positive regulation of cytoplasmic translational elongation (GO:1900249), regulation of stem cell division (GO:2000035), regulation of stem cell differentiation (GO:2000736), cytoplasmic translation (GO:0002181)

GO Molecular Function (9): zinc ion binding (GO:0008270), protein-lysine N-methyltransferase activity (GO:0016279), histone H4K20 methyltransferase activity (GO:0042799), histone H4K20 trimethyltransferase activity (GO:0140943), histone H3K36 trimethyltransferase activity (GO:0140955), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
transposable element silencing	1
constitutive heterochromatin formation	1
cytoplasmic translational elongation	1
positive regulation of translational elongation	1
regulation of cytoplasmic translational elongation	1
stem cell division	1
regulation of cell division	1
regulation of cell differentiation	1
stem cell differentiation	1
translation	1
transition metal ion binding	1
protein methyltransferase activity	1
lysine N-methyltransferase activity	1
protein-lysine N-methyltransferase activity	1
histone H4 methyltransferase activity	1
histone H4K20 methyltransferase activity	1
histone H3K36 methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1911 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMYD5	SMYD4	Q8IYR2	845
SMYD5	SMYD1	Q8NB12	769
SMYD5	NCOR1	O75376	592
SMYD5	SMYD3	Q9H7B4	539
SMYD5	SMYD2	Q9NRG4	524
SMYD5	DEAF1	O75398	523
SMYD5	SETD3	Q86TU7	504
SMYD5	PRDM4	Q9UKN5	494
SMYD5	KMT5B	Q4FZB7	493
SMYD5	PRDM15	P57071	490
SMYD5	SUV39H2	Q9H5I1	476
SMYD5	KMT2E	Q8IZD2	458
SMYD5	SETD1B	Q9UPS6	453
SMYD5	PRDM13	Q9H4Q3	449
SMYD5	SETD4	Q9NVD3	448

IntAct

18 interactions, top by confidence:

A	B	Type	Score
SMYD5	ZNF587	psi-mi:“MI:0915”(physical association)	0.560
SMYD5	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
SMYD5	Ppargc1a	psi-mi:“MI:0915”(physical association)	0.540
SMYD5	Ppargc1a	psi-mi:“MI:0213”(methylation reaction)	0.540
PEA15	SMYD5	psi-mi:“MI:0915”(physical association)	0.400
XRCC5	BACC1	psi-mi:“MI:0914”(association)	0.350
TMEM132A	WWP2	psi-mi:“MI:0914”(association)	0.350
SMYD5	DCD	psi-mi:“MI:0914”(association)	0.350
MAST1	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
UBA52	FUOM	psi-mi:“MI:0914”(association)	0.350
SMYD5	TUB	psi-mi:“MI:0914”(association)	0.350
ZNF417	SMYD5	psi-mi:“MI:0915”(physical association)	0.000
ZNF587	SMYD5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): SMYD5 (Affinity Capture-RNA), SMYD5 (Affinity Capture-RNA), SMYD5 (Affinity Capture-MS), SMYD5 (Affinity Capture-MS), SMYD5 (Affinity Capture-RNA), ZNF417 (Two-hybrid), ZNF587 (Two-hybrid), SMYD5 (Proximity Label-MS), SMYD5 (Affinity Capture-MS), SMYD5 (Affinity Capture-MS), SMYD5 (Affinity Capture-MS), DAK (Affinity Capture-MS), SMYD5 (Affinity Capture-MS), ZNF430 (Affinity Capture-MS), ZNF446 (Affinity Capture-MS)

ESM2 similar proteins: A4IG72, A6QQ71, B3DNN5, C3RZA1, D3ZQF4, E1C5V0, F1RET2, F6PHZ6, O75344, O94952, O95801, P27612, P54319, P97443, Q0P585, Q3TYX3, Q3U3W5, Q3UR70, Q5BJI7, Q5F3K0, Q5R5S1, Q5R5X9, Q5R673, Q5RGL7, Q5ZIZ2, Q6GMV2, Q6GN68, Q6GPQ4, Q6P2P2, Q7M6Z3, Q7T3P8, Q7ZXV5, Q8BTK5, Q8IUF8, Q8IYR2, Q8NB12, Q8NHP6, Q8R5A0, Q8VDH1, Q8WUH2

Diamond homologs: A3M0J3, A5DQN2, A6ZTB4, A7TPV3, F4K1J4, O74467, P38890, Q54D67, Q5A1M3, Q5RGL7, Q5UNT8, Q6BSV3, Q6CX91, Q6FTT0, Q6GMV2, Q75BF1, Q9CWR2, Q9H7B4, A9CPT4, C3RZA1, D3ZKV9, E1C5V0, F1QN74, F1RET2, P97443, Q0P585, Q12529, Q3TYX3, Q4VC12, Q5BJI7, Q5F3V0, Q5R5X9, Q5ZIZ2, Q6C9E7, Q6GN68, Q6GPQ4, Q7M6Z3, Q7TSV3, Q7ZXV5, Q8BTK5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1754 predictions. Top by Δscore:

Variant	Effect	Δscore
2:73214360:AAGGT:A	donor_loss	1.0000
2:73214363:G:GA	donor_loss	1.0000
2:73220658:CA:C	acceptor_loss	1.0000
2:73220659:A:AC	acceptor_loss	1.0000
2:73220659:AGGT:A	acceptor_gain	1.0000
2:73220660:GGTG:G	acceptor_gain	1.0000
2:73220779:GGAG:G	donor_gain	1.0000
2:73220780:GAGG:G	donor_gain	1.0000
2:73220783:G:GA	donor_loss	1.0000
2:73220783:G:GG	donor_gain	1.0000
2:73221159:CCCCA:C	acceptor_loss	1.0000
2:73221160:CCCAG:C	acceptor_loss	1.0000
2:73221161:CCA:C	acceptor_loss	1.0000
2:73221163:A:AG	acceptor_gain	1.0000
2:73221163:A:T	acceptor_loss	1.0000
2:73221164:G:GA	acceptor_loss	1.0000
2:73221164:G:GG	acceptor_gain	1.0000
2:73221164:GGA:G	acceptor_gain	1.0000
2:73221164:GGAGT:G	acceptor_gain	1.0000
2:73221232:CAGGT:C	donor_loss	1.0000
2:73221233:AGGT:A	donor_loss	1.0000
2:73221234:GGTG:G	donor_loss	1.0000
2:73221235:G:GA	donor_loss	1.0000
2:73221236:T:A	donor_loss	1.0000
2:73221822:GCAG:G	acceptor_loss	1.0000
2:73221823:CAGGC:C	acceptor_loss	1.0000
2:73221824:A:AG	acceptor_gain	1.0000
2:73221825:G:A	acceptor_loss	1.0000
2:73221825:G:GG	acceptor_gain	1.0000
2:73221825:GGC:G	acceptor_gain	1.0000

AlphaMissense

2775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:73223105:A:C	S259R	0.999
2:73223426:C:A	S259R	0.999
2:73223426:C:G	S259R	0.999
2:73224873:C:A	H316Q	0.999
2:73224873:C:G	H316Q	0.999
2:73224877:T:C	C318R	0.999
2:73224889:G:C	A322P	0.999
2:73225685:C:A	R364S	0.999
2:73225815:T:C	C376R	0.999
2:73218945:T:A	W61R	0.998
2:73218945:T:C	W61R	0.998
2:73220778:T:A	W155R	0.998
2:73220778:T:C	W155R	0.998
2:73221193:A:C	S166R	0.998
2:73221195:C:A	S166R	0.998
2:73221195:C:G	S166R	0.998
2:73223439:T:A	W264R	0.998
2:73223439:T:C	W264R	0.998
2:73223958:T:C	F299L	0.998
2:73223960:T:A	F299L	0.998
2:73223960:T:G	F299L	0.998
2:73223973:G:A	G304R	0.998
2:73223973:G:C	G304R	0.998
2:73223980:G:A	G306D	0.998
2:73224871:C:G	H316D	0.998
2:73224872:A:G	H316R	0.998
2:73224878:G:A	C318Y	0.998
2:73224901:T:C	F326L	0.998
2:73224903:T:A	F326L	0.998
2:73224903:T:G	F326L	0.998

dbSNP variants (sampled 300 via entrez): RS1000074679 (2:73219650 G>A), RS1000294311 (2:73213425 G>T), RS1000345079 (2:73225271 G>A), RS1000662523 (2:73224655 G>A), RS1000963312 (2:73226700 T>C), RS1001011999 (2:73214029 CTG>C), RS1001081314 (2:73218049 C>G,T), RS1001124678 (2:73219535 C>T), RS1001239064 (2:73219346 T>C), RS1001894991 (2:73213323 C>T), RS1002028483 (2:73223523 A>G,T), RS1002063604 (2:73223320 G>A,C,T), RS1002126937 (2:73221062 T>C,G), RS1002140233 (2:73226191 C>G,T), RS1002243078 (2:73220814 T>C,G)

Disease associations

OMIM: gene MIM:619114 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725091 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
trichostatin A	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697306	Binding	Inhibition of SMYD5 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1QD	HyCyte Hep-G2 KO-hSMYD5	Cancer cell line	Male
CVCL_TP75	HAP1 SMYD5 (-) 1	Cancer cell line	Male
CVCL_XT60	HAP1 SMYD5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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