PRDM16: A Key Regulator of Brown Adipose Tissue and Cardiac Development
Comprehensive genomic and functional analysis of the PRDM16 gene, its role in adipogenesis, cardiomyopathy, and cancer.
Gene Information Card
| Symbol | PRDM16 |
|---|---|
| Full Name | PR/SET domain 16 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.32 |
| NCBI Gene ID | 63976 ncbi.nlm.nih.gov/gene/63976 |
| Ensembl ID | ENSG00000142611 |
| UniProt ID | Q9HAZ2 |
| OMIM ID | 605557 |
| HGNC ID | 14000 |
| Aliases | MEL1, EVS, PFM13, KMT8F |
Description
PRDM16 (PR/SET domain 16) encodes a zinc finger transcription factor that acts as a key molecular switch between brown and white adipose tissue development. It also plays critical roles in cardiac development, hematopoiesis, and is implicated in acute myeloid leukemia and dilated cardiomyopathy. The protein contains an N-terminal PR domain (similar to SET methyltransferases) and multiple C2H2 zinc finger motifs.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy 1LL (CMD1LL) | Loss-of-function mutations in PRDM16 disrupt cardiac gene expression programs, leading to impaired myocardial development and contractile dysfunction. | OMIM #615373; ClinVar |
| Acute myeloid leukemia (AML) | Chromosomal rearrangements (e.g., t(1;3)(p36;q21)) result in PRDM16 fusion proteins (e.g., PRDM16/RPN1) that drive leukemogenesis through aberrant transcriptional activation. | COSMIC; NCBI; PMID: 10655551 |
| Myelodysplastic syndrome (MDS) | PRDM16 overexpression due to 1p36 rearrangements contributes to clonal expansion of hematopoietic progenitors. | COSMIC; PMID: 12411313 |
| Obesity and metabolic disorders | PRDM16 promotes brown/beige adipocyte differentiation; reduced expression is linked to decreased energy expenditure and increased adiposity. | PMID: 19037247; PMID: 22960636 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brown adipose tissue | 45.2 | High |
| Heart | 32.1 | High |
| Skeletal muscle | 18.7 | Medium |
| Kidney | 12.3 | Medium |
| Liver | 2.1 | Low |
| Lung | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 78.5 | High expression; consistent with role in hematopoiesis |
| HepG2 (liver) | 3.2 | Low expression |
| A549 (lung) | 2.1 | Low expression |
| MCF7 (breast) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.268C>T (p.Arg90*) | Nonsense | <0.01% (gnomAD) | Loss-of-function; associated with dilated cardiomyopathy |
| c.1015G>A (p.Gly339Arg) | Missense | <0.01% (gnomAD) | Likely pathogenic; disrupts zinc finger domain |
| t(1;3)(p36;q21) | Chromosomal translocation | Rare in AML | Creates PRDM16-RPN1 fusion; gain-of-function in leukemia |
| c.1234_1235insA | Frameshift | <0.01% (gnomAD) | Loss-of-function; reported in cardiomyopathy |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg90*, c.1234_1235insA) lead to haploinsufficiency, impairing cardiac development and causing dilated cardiomyopathy.
Gain of Function (GOF)
Chromosomal translocations (e.g., t(1;3)) produce fusion proteins that aberrantly activate transcription, driving leukemogenesis in AML.
Dominant Negative (DN)
Not well documented; some missense mutations in the zinc finger domain may interfere with wild-type PRDM16 DNA binding, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Adipogenesis (brown fat cell differentiation)
• PPAR signaling pathway
• Transcriptional misregulation in cancer
• Cardiac progenitor differentiation
Protein Summary
PRDM16 is a 1276-amino acid nuclear protein with an N-terminal PR domain (similar to histone methyltransferases) and 10 C2H2 zinc fingers. It functions as a transcriptional regulator that promotes brown/beige adipocyte differentiation by coactivating PPARGC1A and PPRARG, while repressing white adipocyte genes. In the heart, it is essential for cardiomyocyte proliferation and maturation. In hematopoiesis, it maintains stem cell quiescence; its dysregulation leads to leukemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRDM16 Knockout HEK293 Cell Line | EDJ-KQ3350 | Human | 63976 | Details Get a Quote |
| PRDM16 Knockout HCT 116 Cell Line | EDJ-KQ25007 | Human | 63976 | Details Get a Quote |
| PRDM16 Knockout HeLa Cell Line | EDJ-KQ57009 | Human | 63976 | Details Get a Quote |
| PRDM16 Knockout A-549 Cell Line | EDJ-KQ65514 | Human | 63976 | Details Get a Quote |
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