PRDM16

Summary

PRDM16 (PR/SET domain 16, HGNC:14000) is a protein-coding gene on chromosome 1p36.32, encoding Histone-lysine N-methyltransferase PRDM16 (Q9HAZ2). Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.

The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 63976 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Strong, ClinGen) — +3 more curated relationships
• GWAS associations: 74
• Clinical variants (ClinVar): 1,559 total — 10 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 115
• Druggable target: yes
• Cancer driver (intOGen): ambiguous (mixed evidence) across 1 cancer types
• MANE Select transcript: NM_022114

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14000
Approved symbol	PRDM16
Name	PR/SET domain 16
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Aliases	MEL1, PFM13, KIAA1675, MGC166915, KMT8F
Ensembl gene	ENSG00000142611
Ensembl biotype	protein_coding
OMIM	605557
Entrez	63976

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000270722, ENST00000378389, ENST00000378391, ENST00000463591, ENST00000509860, ENST00000511072, ENST00000512462, ENST00000514189, ENST00000606170, ENST00000607632

RefSeq mRNA: 2 — MANE Select: NM_022114 NM_022114, NM_199454

CCDS: CCDS41236, CCDS44048

Canonical transcript exons

ENST00000270722 — 17 exons

Exon	Start	End
ENSE00001754112	3186125	3186474
ENSE00001759023	3433677	3438621
ENSE00003480863	3244087	3244137
ENSE00003695658	3411384	3412800
ENSE00003695725	3385152	3385286
ENSE00003696962	3402791	3402998
ENSE00003698226	3430872	3431108
ENSE00003698430	3418667	3418744
ENSE00003699052	3417828	3417997
ENSE00003699796	3425581	3425750
ENSE00003700221	3396491	3396593
ENSE00003700645	3405495	3405648
ENSE00003700688	3404739	3404886
ENSE00003700833	3431966	3432140
ENSE00003701451	3414560	3414647
ENSE00003701891	3426051	3426225
ENSE00003850248	3069203	3069296

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 97.13.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2875 / max 56.1660, expressed in 658 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
276	1.3205	454
275	0.8361	422
274	0.1309	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.13	gold quality
pigmented layer of retina	UBERON:0001782	92.97	gold quality
ascending aorta	UBERON:0001496	87.94	gold quality
thoracic aorta	UBERON:0001515	87.93	gold quality
descending thoracic aorta	UBERON:0002345	87.79	gold quality
aorta	UBERON:0000947	87.31	gold quality
ventricular zone	UBERON:0003053	87.22	gold quality
popliteal artery	UBERON:0002250	86.87	gold quality
tibial artery	UBERON:0007610	86.84	gold quality
right coronary artery	UBERON:0001625	85.14	gold quality
epithelial cell of pancreas	CL:0000083	84.77	gold quality
left coronary artery	UBERON:0001626	83.42	gold quality
coronary artery	UBERON:0001621	82.95	gold quality
oviduct epithelium	UBERON:0004804	82.88	gold quality
renal medulla	UBERON:0000362	81.48	gold quality
embryo	UBERON:0000922	79.95	gold quality
ganglionic eminence	UBERON:0004023	79.95	gold quality
tibial nerve	UBERON:0001323	79.86	gold quality
body of stomach	UBERON:0001161	79.79	gold quality
right lobe of thyroid gland	UBERON:0001119	79.68	gold quality
thyroid gland	UBERON:0002046	79.15	gold quality
apex of heart	UBERON:0002098	79.14	gold quality
left lobe of thyroid gland	UBERON:0001120	78.98	gold quality
stomach	UBERON:0000945	78.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.38	gold quality
heart left ventricle	UBERON:0002084	77.38	gold quality
cardiac ventricle	UBERON:0002082	76.95	gold quality
visceral pleura	UBERON:0002401	75.65	gold quality
dorsal root ganglion	UBERON:0000044	75.28	gold quality
body of pancreas	UBERON:0001150	74.89	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	15.15
E-ANND-3	yes	6.12
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CLC
CSF3
DIO2	Activation
EIF3K
HGF
PPARGC1A
PRDM16

Upstream regulators (CollecTRI, top): BMP7, HES1, HOXA10, HOXA9, HOXB4, LMO2, PPARA, PRDM16

miRNA regulators (miRDB)

299 targeting PRDM16, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372

Literature-anchored findings (GeneRIF, showing 40)

• Breakpoints occurring in the first intron and in the 5’ region of the MEL1 gene associated with the t(1;3)(p36;q21) translocation have been found in three myelodysplastic syndrome/acute myelogenous leukemia patients. (PMID:12557231)
• structure, expression pattern, and function of MEL1 in leukemia cells; overexpression of the zinc finger protein lacking the PR domain (EVI1 and MEL1S)is likely one of the causative factors in the pathogenesis of myeloid leukemia. (PMID:12816872)
• Aberrant gene expression associated with DNA hypomethylation is implicated in leukemogenesis of adult T-cell leukemia. (PMID:14656887)
• Correction opf X-linked chronic granulomatous disease by gene therapy was augmented by insertional activation of PRDM16. (PMID:16582916)
• A 3’ RACE experiments followed by sequence-specific RT-PCR resulted in the identification of the PRDM16 gene as a novel fusion partner of the RUNX1 gene in a patient with rare t(1;21)(p36;q22). (PMID:16598304)
• RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance (PMID:18202228)
• array CGH performed on CD34(+) cells revealed cryptic partial deletions of PRDM16. (PMID:18767145)
• SKI and MEL1 knockdown synergistically restored TGF-beta responsiveness in MKN28 cells and reduced tumor growth in vivo (PMID:19049980)
• PRDM16 controls a bidirectional cell fate switch between skeletal myoblasts and brown adipocytes. (PMID:19285866)
• PRDM16 and PGC-1 alpha expression was 2-fold greater in epicardial than sc fat. (PMID:19567523)
• data indicate that the PRDM16-C/EBP-beta complex initiates brown fat formation from myoblastic precursors (PMID:19641492)
• Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus (PMID:22039459)
• Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. (PMID:22050763)
• genome-wide association studies have successfully identified four new genetic variants associated with migraine in the LRP1, TRPM8, and PRDM16 genes (PMID:22072275)
• genetic association studies in a Chinese Xinjiang Uygur population: Studies suggest that commonly occurring SNP in PRDM16 (rs2236518) shows a significant negative association with metabolic syndrome in a multivariable logistic regression analysis. (PMID:22383139)
• Data identify Prdm3 and Prdm16 as H3K9me1 methyltransferases and expose a functional framework in which anchoring to the nuclear periphery helps maintain the integrity of mammalian heterochromatin. (PMID:22939622)
• High PRDM16 expression is associated with pheochromocytoma. (PMID:23454374)
• Single nucleotide polymorphism Rs2236518 is associated with body mass index in the young Chinese males (using QTDT), and the older Chinese males (using GLM-ANOVA). (PMID:23524569)
• Mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic left ventricular noncompaction cardiomyopathy and dilated cardiomyopathy. (PMID:23768516)
• The rs2651899 variant in PRDM16 plays a role in Chinese common migraine susceptibility. (PMID:24021092)
• No association between the four polymorphisms of the PRDM16 gene with essential hypertension. (PMID:24327154)
• An association between PRDM16 rs2651899 SNP and migraine in a Swedish case-control study. (PMID:24674449)
• Mutations in gene encoding the transcriptional co-activator PRDM16 may be a cause of left-ventricular noncompaction and dilated cardiomyopathy. (PMID:24717670)
• Genetic analyses uncovered the importance of the PRDM16 gene in the regulation of lean body mass. (PMID:24863034)
• PRDM2, PRDM5, PRDM16 promoters are methylated and their expression is suppressed in lung cancer cells. (PMID:24966940)
• Three novel loci were identified in East Asians with cardiac arrhythmias: rs2483280 (PRDM16 locus) and rs335206 (PRDM6 locus) were associated with QRS duration; and rs17026156 (SLC8A1 locus) correlated with PR interval. (PMID:25035420)
• EVI1 and MEL1 are homolog genes whose transcriptional activations by chromosomal translocations have roles in Japanese pediatric acute myeloid leukemia (PMID:25567132)
• MED1 is required for optimal PRDM16-induced Ucp1 expression (PMID:25644605)
• PRDM16 might contribute to maintain adipose tissue “white fat” gene expression profile and systemic metabolic homeostasis. (PMID:25662275)
• A single risk variant, rs2651899 in PRDM16, was significantly associated with efficacy of triptans in migraine patients (PMID:26502740)
• Our results suggest that K568 SUMOylation of sPRDM16 plays an important role in the progression of acute myeloid leukemia. (PMID:26559765)
• Results show that PRDM16 overexpression was highly recurrent in de novo paediatric AML and is associated with adverse outcome (PMID:26684393)
• High PRDM16 expression is associated with astrocytoma. (PMID:26701852)
• Flow cytometric analysis and western blot analysis of apoptosisassociated proteins indicated that PRDM16 has an antiapoptotic role in prostatic cancer cells. In addition, the spliced form, sPRDM16/MEL1S, was detected to be overexpressed in PCa cell lines. In conclusion, the present study indicated an important oncogenic role in prostate cancer. (PMID:27511603)
• Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially migraine without aura , among Chinese patients. It appears that there is no association with serotonin receptor related genes. (PMID:28058730)
• Prdm16 interacts with the transcription factor Hlx, which is stabilized in response to beta3-adrenergic signaling, to increase thermogenic gene expression and mitochondrial biogenesis in subcutaneous WAT. (PMID:28701693)
• High PRDM16 expression is a significant predictive marker for poor prognosis in adult AML patients. (PMID:28710806)
• Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1alpha and PRDM16 mRNA (PMID:28824327)
• Results identify a modifying enzyme for Prdm16, and they demonstrate a central role of Cbx4 in the control of Prdm16 stability and white fat browning. (PMID:29539416)
• Study revealed that LINC00982 and PRDM16 may serve as biomarkers or potential drug targets for the diagnosis and therapy of lung adenocarcinoma. (PMID:30132554)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prdm16	ENSMUSG00000039410
rattus_norvegicus	Prdm16	ENSRNOG00000045913

Paralogs (1): MECOM (ENSG00000085276)

Protein

Protein identifiers

Histone-lysine N-methyltransferase PRDM16 — Q9HAZ2 (reviewed: Q9HAZ2)

Alternative names: PR domain zinc finger protein 16, PR domain-containing protein 16, Transcription factor MEL1

All UniProt accessions (5): Q9HAZ2, D6RDW0, D6RFY3, H0YA13, U3KQL6

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context. In the cytoplasm, acts as a histone methyltransferase, which catalyzes monomethylation of ‘Lys-9’ of free histone H3 (H3K9me1) during translation. Monomethylated histone H3 is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases (SUV39H1 and SUV39H2) use it as a substrate to catalyze histone H3 ‘Lys-9’ trimethylation (H3K9me3). Probably one of the primary histone methyltransferases along with MECOM/PRDM3 that direct cytoplasmic H3K9me1 methylation. In the nucleus, acts as a key chromatin adapter that mediates differentiation of brown and beige adipocytes, which are specialized in dissipating chemical energy in the form of heat in response to cold or excess feeding. Following recruitment to chromatin by PPARG nuclear receptor, promotes differentiation of myoblastic precursors into brown adipose cells. Mechanistically, acts by mediating recruitment of (1) EHMT1 histone methyltransferase, thereby inhibiting the expression of white adipose-selective genes or (2) mediator complex, activating genes that are highly expressed in brown adipocytes, such as UCP1, PPARA, and PPARGC1A. Also mediates differentiation of beige adipocytes from white adipose cells following recruitment by PPARG. In addition to adipocyte differentiation, also involved in tolerance to gut microbiota: following recruitment to chromatin by RORgammaT (RORC) in a subset of antigen-presenting cells, promotes differentiation of peripherally-induced regulatory T-cells (pTreg), which suppress inflammatory responses to commensal microorganisms. Also required in adult heart to preserve mitochondrial function and inhibit hypertrophy with advanced age. Functions as a repressor of TGF-beta signaling. Binds DNA and functions as a transcriptional regulator. Functions as a repressor of TGF-beta signaling. May regulate granulocyte differentiation.

Subunit / interactions. Interacts with CEBPA, CEBPB and CEBPD; the interaction is direct. Interacts with PPARG; controls brown adipocytes. Interacts with CTBP1 and CTBP2; represses the expression of white adipose tissue-specific genes. Interacts (via N-terminus) with RBBP4. Interacts with PPARGC1A and PPARGC1B; interaction with PPARGC1A or PPARGC1B activates the transcription of brown adipose tissue-specific gene. Interacts with HDAC1, SKI and SMAD2; the interaction with SKI promotes the recruitment of SMAD3-HDAC1 complex on the promoter of TGF-beta target genes. Interacts with ZNF516; the interaction is direct and may play a role in the transcription of brown adipose tissue-specific gene. Interacts with EHMT1; promoting PRDM16 stability by preventing its ubiquitination and degradation. Interacts with MED1; promoting recruitment of the mediator complex. Interacts with TLE3; preventing association between PRDM16 and PPARG and differentiation into brown adipose cells. Interacts (when phosphorylated) with PIN1; promoting PRDM16 degradation. Interacts with DHRS7B; preventing association between PRDM16 and PPARG and differentiation into brown adipose cells.

Subcellular location. Nucleus. Chromosome. Cytoplasm.

Tissue specificity. Expressed in uterus and kidney. Expressed in both cardiomyocytes and interstitial cells.

Post-translational modifications. Acetylation at Lys-915 py EP300/p300 abolishes its association with PPARG and ability to promote differentiation of brown adipocytes. Deacetylated by HDAC6. Phosphorylated; phosphorylation promotes interaction with PIN1 and degradation. Ubiquitinated by the CRL2(APPBP2) complex, leading to its degradation by the proteasome. Interaction with EHMT1 promotes PRDM16 stability by preventing interaction with APPBP2 and subsequent ubiquitination. Sumoylated by CBX4, promoting its stabilization by preventing PRDM16 ubiquitination and degradation.

Disease relevance. Left ventricular non-compaction 8 (LVNC8) [MIM:615373] A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC8 is an autosomal dominant condition. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 1LL (CMD1LL) [MIM:615373] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving PRDM16 is found in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Reciprocal translocation t(1;3)(p36;q21). Isoform 4 is specifically expressed in adult T-cell leukemia.

Miscellaneous. Produced by alternative promoter usage.

Similarity. Belongs to the PRDM16 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9HAZ2-1	1	yes
Q9HAZ2-2	2, MEL1L
Q9HAZ2-3	3
Q9HAZ2-4	4, MEL1S

RefSeq proteins (2): NP_071397, NP_955533 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044410	PRDM16_PR-SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF13912, PF21549

Enzyme classification (BRENDA):

• EC 2.1.1.367 — [histone H3]-lysine9 N-methyltransferase (BRENDA: 5 organisms, 4 substrates, 19 inhibitors, 0 Km, 0 kcat entries)
• EC 2.1.1.370 — [histone H3]-lysine4 N-dimethyltransferase (BRENDA: 2 organisms, 6 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (64 total): zinc finger region 10, sequence variant 8, region of interest 7, compositionally biased region 7, cross-link 7, strand 7, splice variant 4, sequence conflict 4, turn 4, helix 3, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6BW4	X-RAY DIFFRACTION	2
2N1I	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAZ2-F1	51.73	0.00

Functional residue map

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

Post-translational modifications (8): 915, 122, 321, 578, 778, 790, 832, 915

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2

MSigDB gene sets: 540 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_TOLERANCE_INDUCTION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, MAZ_Q6, GOBP_WHITE_FAT_CELL_DIFFERENTIATION, TGACCTY_ERR1_Q2, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, AP2_Q3, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, CEBPB_01

GO Biological Process (21): negative regulation of transcription by RNA polymerase II (GO:0000122), tolerance induction in gut-associated lymphoid tissue (GO:0002394), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of granulocyte differentiation (GO:0030853), methylation (GO:0032259), regulation of cellular respiration (GO:0043457), regulatory T cell differentiation (GO:0045066), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), brown fat cell differentiation (GO:0050873), negative regulation of muscle cell differentiation (GO:0051148), protein maturation (GO:0051604), heterochromatin organization (GO:0070828), protein localization to chromatin (GO:0071168), positive regulation of cold-induced thermogenesis (GO:0120162), beige fat cell differentiation (GO:0160274), negative regulation of white fat cell differentiation (GO:0160275), chromatin remodeling (GO:0006338), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (21): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), histone H3K9 methyltransferase activity (GO:0046974), DNA-binding transcription factor binding (GO:0140297), chromatin-protein adaptor activity (GO:0140463), histone H3 methyltransferase activity (GO:0140938), histone H3K9 monomethyltransferase activity (GO:0140948), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), metal ion binding (GO:0046872), histone H3K9me2 methyltransferase activity (GO:0140947)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), aggresome (GO:0016235), transcription repressor complex (GO:0017053)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Transcriptional regulation of brown and beige adipocyte differentiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
cellular anatomical structure	4
chromatin organization	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
fat cell differentiation	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
transcription regulator activity	2
transcription coregulator activity	2
regulation of transcription by RNA polymerase II	1
immune response in gut-associated lymphoid tissue	1
tolerance induction in mucosal-associated lymphoid tissue	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of myeloid leukocyte differentiation	1
granulocyte differentiation	1
regulation of granulocyte differentiation	1
metabolic process	1
regulation of generation of precursor metabolites and energy	1
cellular respiration	1
T cell differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
muscle cell differentiation	1
negative regulation of cell differentiation	1
regulation of muscle cell differentiation	1
gene expression	1
protein metabolic process	1
protein localization to chromosome	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
negative regulation of fat cell differentiation	1
white fat cell differentiation	1
cellular developmental process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1

Protein interactions and networks

STRING

2402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM16	PPARG	P37231	996
PRDM16	PPARGC1A	Q9UBK2	995
PRDM16	CEBPB	P17676	995
PRDM16	EHMT1	Q9H9B1	959
PRDM16	UCP1	P25874	946
PRDM16	CTBP1	Q13363	928
PRDM16	CIDEA	O60543	880
PRDM16	PPARGC1B	Q86YN6	872
PRDM16	CTBP2	P56545	863
PRDM16	ZNF516	Q92618	826
PRDM16	TMEM26	Q6ZUK4	795
PRDM16	MYF5	P13349	792
PRDM16	EBF2	Q9HAK2	779
PRDM16	BMP7	P18075	778
PRDM16	DIO2	Q92813	778

IntAct

21 interactions, top by confidence:

A	B	Type	Score
PRDM16	RBBP4	psi-mi:“MI:0407”(direct interaction)	0.620
RBBP4	PRDM16	psi-mi:“MI:0407”(direct interaction)	0.620
PRDM16	H3-4	psi-mi:“MI:0915”(physical association)	0.400
BTBD17	PRDM16	psi-mi:“MI:0915”(physical association)	0.400
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
PRDM16	GAPDHS	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
	ARID1A	psi-mi:“MI:0914”(association)	0.350
SPDEF	SLC4A2	psi-mi:“MI:0914”(association)	0.350
PRDM16	CTBP2	psi-mi:“MI:0914”(association)	0.350
CTBP1	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270
HOXB2	KMT2D	psi-mi:“MI:2364”(proximity)	0.270
ELK3	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
KLF12		psi-mi:“MI:2364”(proximity)	0.270
KLF3	MCRIP1	psi-mi:“MI:2364”(proximity)	0.270
SOX6	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (210): PRDM16 (Affinity Capture-MS), PRDM16 (Affinity Capture-MS), CTBP2 (Affinity Capture-MS), CTBP1 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), SLC25A13 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), TBL3 (Affinity Capture-MS), SON (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), PFKL (Affinity Capture-MS), MAP1B (Affinity Capture-MS), ATP2A2 (Affinity Capture-MS), SLC25A11 (Affinity Capture-MS), ATP5O (Affinity Capture-MS)

ESM2 similar proteins: A0PJY2, A1YPR0, A2A935, B0K011, B0X9H6, B7ZRU9, O13089, O15090, O15156, O75626, O88939, O93567, O95365, P14404, P25932, P41183, P56260, Q03112, Q08DS3, Q0IHB8, Q1L8W0, Q2VWH6, Q32NK7, Q3T135, Q5XJQ7, Q60636, Q64321, Q6AY34, Q6DBW0, Q6F2E4, Q802Y8, Q8I7Z8, Q8K083, Q8N9L1, Q8NAP8, Q8TBJ5, Q8VCZ7, Q8VDL9, Q98T94, Q99PV8

Diamond homologs: A0A163UT06, A2A935, A2AGX3, A2AJ77, B8A5Y1, E9Q3T6, O75626, P0C6Y7, P14404, Q03112, Q13029, Q3UZD5, Q60636, Q63755, Q6P2A1, Q8BZ97, Q96EQ9, Q9GZV8, Q9H4Q4, Q9HAZ2, Q9NQV5, Q9NQV7, Q9NQV8, Q9NQW5, B7ZRM8, B7ZRU9, Q22024, Q8I7Z8, B1WBU4, A6QPM3, Q9NQX0, Q9NQX1, P80944, Q29419, Q7TS63, Q9CXE0, Q9P243, E9PZZ1, Q9H4Q3, Q3US17

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PRDM16	up-regulates	Brown_adipogenesis
PRDM16	up-regulates	PPARG	binding
PRDM16	down-regulates	Skeletal_muscle_differentiation
BMP7	“up-regulates quantity by expression”	PRDM16	“transcriptional regulation”
PRDM16	up-regulates	SKI	binding
BMP7	up-regulates	PRDM16	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: ambiguous (mixed evidence) across 1 cancer types — PCM.

Clinical variants and AI predictions

ClinVar

1559 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	7
Uncertain significance	781
Likely benign	560
Benign	74

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1029845	NM_022114.4(PRDM16):c.534C>A (p.Cys178Ter)	Pathogenic
1675068	NM_022114.4(PRDM16):c.1627C>T (p.Gln543Ter)	Pathogenic
3340802	NM_022114.4(PRDM16):c.559C>T (p.Gln187Ter)	Pathogenic
377306	NM_022114.4(PRDM16):c.827del (p.Gly276fs)	Pathogenic
3906534	NM_022114.4(PRDM16):c.676+2T>C	Pathogenic
426516	NM_022114.4(PRDM16):c.1459del (p.Glu487fs)	Pathogenic
60724	NM_022114.4(PRDM16):c.2104A>T (p.Lys702Ter)	Pathogenic
60725	NM_022114.4(PRDM16):c.1573dup (p.Arg525fs)	Pathogenic
60729	NM_022114.4(PRDM16):c.2660T>C (p.Leu887Pro)	Pathogenic
986273	NM_022114.4(PRDM16):c.2595dup (p.Ile866fs)	Pathogenic
1710027	NM_022114.4(PRDM16):c.2434del (p.Arg812fs)	Likely pathogenic
2582631	NM_022114.4(PRDM16):c.3142del (p.Leu1048fs)	Likely pathogenic
3062115	NM_022114.4(PRDM16):c.2134C>T (p.Gln712Ter)	Likely pathogenic
3370518	NM_022114.4(PRDM16):c.2861+1G>T	Likely pathogenic
3391827	GRCh37/hg19 1p36.32(chr1:3101762-3155604)x1	Likely pathogenic
4088196	NM_022114.4(PRDM16):c.885-1G>A	Likely pathogenic
524100	NM_022114.4(PRDM16):c.1989del (p.Glu664fs)	Likely pathogenic

SpliceAI

7713 predictions. Top by Δscore:

Variant	Effect	Δscore
1:3069294:AAA:A	donor_gain	1.0000
1:3069295:AA:A	donor_gain	1.0000
1:3069297:G:GG	donor_gain	1.0000
1:3102744:G:GG	donor_gain	1.0000
1:3244085:A:AG	acceptor_gain	1.0000
1:3244086:G:GG	acceptor_gain	1.0000
1:3244086:GCA:G	acceptor_gain	1.0000
1:3244086:GCAA:G	acceptor_gain	1.0000
1:3402786:T:TA	acceptor_gain	1.0000
1:3402786:TGCA:T	acceptor_loss	1.0000
1:3402787:GCA:G	acceptor_loss	1.0000
1:3402789:A:AG	acceptor_gain	1.0000
1:3402789:A:AT	acceptor_loss	1.0000
1:3402789:AGAG:A	acceptor_gain	1.0000
1:3402790:G:GA	acceptor_gain	1.0000
1:3402790:GA:G	acceptor_gain	1.0000
1:3402790:GAGG:G	acceptor_gain	1.0000
1:3402790:GAGGA:G	acceptor_gain	1.0000
1:3402861:G:GT	donor_gain	1.0000
1:3402967:G:GT	donor_gain	1.0000
1:3402993:G:GG	donor_gain	1.0000
1:3404737:A:AG	acceptor_gain	1.0000
1:3404737:AGCCT:A	acceptor_gain	1.0000
1:3404738:G:GG	acceptor_gain	1.0000
1:3404738:GCCT:G	acceptor_gain	1.0000
1:3404738:GCCTG:G	acceptor_gain	1.0000
1:3404884:AAG:A	donor_gain	1.0000
1:3404887:G:GA	donor_loss	1.0000
1:3405649:G:GG	donor_gain	1.0000
1:3069283:G:GT	donor_gain	0.9900

AlphaMissense

8442 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:3404785:T:A	C311S	1.000
1:3404785:T:C	C311R	1.000
1:3404786:G:A	C311Y	1.000
1:3404786:G:C	C311S	1.000
1:3404787:C:G	C311W	1.000
1:3404794:T:A	C314S	1.000
1:3404794:T:C	C314R	1.000
1:3404795:G:C	C314S	1.000
1:3404796:T:G	C314W	1.000
1:3404806:T:C	F318L	1.000
1:3404807:T:C	F318S	1.000
1:3404808:C:A	F318L	1.000
1:3404808:C:G	F318L	1.000
1:3404825:T:C	L324P	1.000
1:3404830:C:A	R326S	1.000
1:3404831:G:C	R326P	1.000
1:3404833:C:A	H327N	1.000
1:3404833:C:G	H327D	1.000
1:3404834:A:C	H327P	1.000
1:3404834:A:G	H327R	1.000
1:3404835:C:A	H327Q	1.000
1:3404835:C:G	H327Q	1.000
1:3404845:C:G	H331D	1.000
1:3404847:C:A	H331Q	1.000
1:3404847:C:G	H331Q	1.000
1:3404863:T:C	F337L	1.000
1:3404865:C:A	F337L	1.000
1:3404865:C:G	F337L	1.000
1:3404869:T:A	C339S	1.000
1:3404869:T:C	C339R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008213 (1:3423137 T>G), RS1000011215 (1:3313628 G>A,C,T), RS1000013132 (1:3294920 C>A), RS1000014309 (1:3204554 C>T), RS1000023317 (1:3378994 CAG>C), RS1000023739 (1:3265069 G>A), RS1000030323 (1:3210863 C>T), RS1000037516 (1:3109071 G>A,T), RS1000039346 (1:3284335 T>C), RS1000044992 (1:3179731 C>T), RS1000045978 (1:3393874 C>G,T), RS1000047847 (1:3343842 C>G,T), RS1000051978 (1:3183323 G>A), RS1000055815 (1:3410977 C>G,T), RS1000063319 (1:3299257 G>A)

Disease associations

OMIM: gene MIM:605557 | disease phenotypes: MIM:615373, MIM:192600, MIM:194200, MIM:614756, MIM:115210

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy	Strong	Autosomal dominant
left ventricular noncompaction 8	Moderate	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
left ventricular noncompaction	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
dilated cardiomyopathy	Strong	AD

Mondo (11): left ventricular noncompaction 8 (MONDO:0014152), dilated cardiomyopathy (MONDO:0005021), microcephaly (MONDO:0001149), cardiac rhythm disease (MONDO:0007263), familial hypertrophic cardiomyopathy (MONDO:0024573), Wolff-Parkinson-White syndrome (MONDO:0008685), cerebellar dysfunction with variable cognitive and behavioral abnormalities (MONDO:0013886), familial restrictive cardiomyopathy (MONDO:0016340), cardiomyopathy, dilated, 1LL (MONDO:0800367), (MONDO:0015470), left ventricular noncompaction (MONDO:0018901)

Orphanet (8): Familial isolated dilated cardiomyopathy (Orphanet:154), Left ventricular noncompaction (Orphanet:54260), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Non-progressive cerebellar ataxia with intellectual disability (Orphanet:314647), Familial restrictive cardiomyopathy (Orphanet:217635), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

115 total (30 of 115 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000055	Abnormal female external genitalia morphology
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000160	Narrow mouth
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000464	Abnormality of the neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior

GWAS associations

74 associations (top):

Study	Trait	p-value
GCST000635_27	Response to statin therapy	2.000000e-06
GCST001105_1	Migraine	4.000000e-09
GCST002081_15	Migraine	4.000000e-14
GCST002533_1	QRS duration	2.000000e-11
GCST002550_1	Allergic rhinitis	7.000000e-07
GCST002759_12	Motion sickness	4.000000e-13
GCST003265_327	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003720_18	Migraine	4.000000e-10
GCST003720_21	Migraine	5.000000e-38
GCST003901_7	Cognitive decline (age-related)	1.000000e-06
GCST003986_27	Migraine	9.000000e-28
GCST004599_238	Mean platelet volume	1.000000e-22
GCST004601_51	Red blood cell count	2.000000e-10
GCST004602_1	Mean corpuscular volume	1.000000e-13
GCST004604_11	Hematocrit	3.000000e-09
GCST004607_3	Plateletcrit	7.000000e-24
GCST004616_102	Platelet distribution width	2.000000e-11
GCST004630_1	Mean corpuscular hemoglobin	4.000000e-14
GCST005194_149	Coronary artery disease	2.000000e-09
GCST005195_94	Coronary artery disease	1.000000e-09
GCST005196_177	Coronary artery disease	2.000000e-09
GCST005337_15	Headache	6.000000e-10
GCST006110_17	Nose morphology	6.000000e-06
GCST006197_7	Type 1 diabetes autoantibodies in high risk HLA genotype individuals (time to event)	6.000000e-06
GCST006227_1	Diastolic blood pressure	1.000000e-08
GCST006228_1	Systolic blood pressure	1.000000e-08
GCST006231_9	Mean arterial pressure	3.000000e-06
GCST007843_1	Rheumatoid arthritis	2.000000e-14
GCST007930_132	Medication use (agents acting on the renin-angiotensin system)	2.000000e-11
GCST007939_10	Medication use (antimigraine preparations)	8.000000e-11

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0006928	motion sickness
EFO:0004713	FEV/FVC ratio
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0000482	event free survival time
EFO:0004866	autoantibody measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009939	Antimigraine preparation use measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0009262	nicotine dependence symptom count
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0005665	white matter hyperintensity measurement
EFO:0004327	electrocardiography
EFO:0004509	hemoglobin measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4742318 (PROTEIN-PROTEIN INTERACTION), CHEMBL5214855 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11807862	PRDM16		0.00	0
rs2651899	PRDM16		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	6
trichostatin A	decreases expression, affects cotreatment	3
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
sodium arsenite	increases expression	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	decreases expression, affects cotreatment	2
Arsenic	affects methylation, decreases methylation	2
Daunorubicin	decreases expression	2
Doxorubicin	decreases expression	2
Mitoxantrone	decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	affects methylation, decreases expression	2
fluorene-9-bisphenol	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects methylation, affects cotreatment	1
tributyltin	affects methylation	1
terbufos	increases methylation	1
beta-lapachone	decreases expression, increases expression	1
arsenite	increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, increases methylation	1
benzo(e)pyrene	affects methylation, increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
tofacitinib	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713782	Binding	Protac activity at CRBN/PRDM16 in human BxPC-3 cells assessed as PRDM16 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8MZ	Abcam HCT 116 PRDM16 KO	Cancer cell line	Male
CVCL_B9AK	Abcam MCF-7 PRDM16 KO	Cancer cell line	Female
CVCL_B9Q8	Abcam A-549 PRDM16 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00146822	PHASE4	COMPLETED	REFLEx Study (ENDOTAK RELIANCE G Evaluation of Handling and Electrical Performance
NCT00187239	PHASE4	COMPLETED	Reduce Ventricular Pacing in Dual Chamber Implantable Cardioverter Defibrillators Using AutoIntrinsic Conduction Search Study
NCT00247533	PHASE4	UNKNOWN	Cerebral Artery Stenosis, Coronary Artery Disease and Arrhythmia
NCT00282620	PHASE4	UNKNOWN	Magnesium to Reduce Implantable Cardioverter Defibrillator (ICD) Shocks and Improve Patient’s Quality of Life.
NCT00290056	PHASE4	UNKNOWN	Effect of Supplemental Intake of Omega-3 Polyunsaturated Fatty Acids on the Rate and Complexity of Spontaneously Occurring Ventricular and Supraventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillator (ICD) - A Randomized Clinical Trial
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00457340	PHASE4	COMPLETED	Atorvastatin For The Reduction Of Ventricular Arrhythmias
NCT00507390	PHASE4	WITHDRAWN	Omega 3 Polyunsaturated Fatty Acid Supplements (PUFAs) and Microvolt T Wave Alternans (TWA) in Patients With Ventricular Arrhythmia
NCT00575523	PHASE4	COMPLETED	Atropine for Prevention of Dysrhythmias Caused by Percutaneous Ethanol Instillation for Hepatoma Therapy
NCT00579098	PHASE4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT01613092	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01628666	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01717469	PHASE4	UNKNOWN	Safety and the Effects of Isolated Left Ventricular Pacing in Patients With Bradyarrhythmias
NCT01819064	PHASE4	COMPLETED	Heart Rate Response to Atropine Doses Less Than 0.1mg IV to Anesthetized Infants
NCT01834872	PHASE4	UNKNOWN	Safety and Feasibility of Arrhythmia Ablation Using the Amigo Remote Robotic System as Compared With Manual Ablation
NCT01841242	PHASE4	COMPLETED	Comparison of Alcoholic Chlorhexidine 2% Versus Alcoholic Povidone Iodine for Infections Prevention With Cardiac Resynchronization Therapy Device Implantation
NCT01991223	PHASE4	UNKNOWN	Dexmedetomidine for Catheter-related Bladder Discomfort
NCT02045173	PHASE4	COMPLETED	Automate Detection of Sleep Apnea by ApneascanTM
NCT02203630	PHASE4	TERMINATED	Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
NCT02565069	PHASE4	COMPLETED	Identification for the Treatment of Complex Arrhythmias
NCT03273634	PHASE4	COMPLETED	The Effect of Proton Pump Inhibition on Palpitations
NCT03289429	PHASE4	UNKNOWN	Antiarrhythmic and Cardioprotective Effects of Atorvastatin Versus Magnesium Sulfate in Cardiac Valve Replacement Surgery
NCT03895411	PHASE4	UNKNOWN	Efficacy and Safety of Sotalol in Children With Arrhythmia
NCT05486377	PHASE4	COMPLETED	Remimazolam vs Desflurane for General Anesthesia for Ablation of Arrhythmia
NCT06574555	PHASE4	COMPLETED	Norepinephrine ED90 Bolus After Spinal Anesthesia in Cesarean Section
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction