PRDM16 (PR domain containing 16)

2004-04-01   Jean-Loup Huret , Sylvie Senon 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
1p36.32
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
CMD1LL,KMT8F,LVNC8,MEL1,PFM13
FUSION GENES

DNA/RNA

Description

spans 369 kb; 17exons; 3827 bp coding sequence.

Transcription

alternative transcripts MEL1 and MEL1S (MEL1 short)

Proteins

Description

17O kDa (MEL1) and 150 Da (MEL1S); like MDS1/EVI1, The MEL1contains a PR domain (homologous to the SET domain present in MLL ) in the N term, two DNA binding domains (made of 7 and 3 zing fingers) separated by a repression domain, and an acidic domain at the C-term.
MEL1S lacks the PR domain, like EVI1 alone.
MEL1 and MEL1S, in a "yin-yang fashion", are hypothezised to display antagonistic properties; the PR domain may act as an inhibitor of tumorigenesis.

Expression

wide, contrarily to what was previously found

Localisation

nuclear

Homology

63% homology with MDS1/EVI1; both are members of the PR domain family

Implicated in

Entity name
t(1;3)(p36;q21) myeloid leukemias --> involving RPN1 and PRDM16
Disease
myelodysplastic syndromes (MDS), acute non lymphoblastic leukemias (AML), therapy-related leukemias and myeloprolifrative syndromes; with features similar to those of the 3q21q26 syndrome, including megakaryocytic dysplasia (see also 3q rearrangements in myeloid malignancies).
Prognosis
very poor
Hybrid gene
juxtaposition of the enhancer of the constitutively expressed housekeeping gene RPN1, normally sitting in 3q21, in 5 of MEL1 on der(1); both genes are orientated telomere to centromere; the same situation occurs between RPN1 in 5 of EVI1 in the t(3;3)(q21;q26) )
Oncogenesis
the translocation results in either an ectopic expression of MEL1 driven by RPN1or by disruption of its PR domain; this probable heterogenity may be associated with different clinical features. The short form, MEL1S, is mainly expressed

Bibliography

Pubmed IDLast YearTitleAuthors
147122372004Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells.Lahortiga I et al
110500052000A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells.Mochizuki N et al
128168722003A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation.Nishikata I et al
89868051996Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas.Weterman MA et al
125572312003Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1.Xinh PT et al

Other Information

Locus ID:

NCBI: 63976
MIM: 605557
HGNC: 14000
Ensembl: ENSG00000142611

Variants:

dbSNP: 63976
ClinVar: 63976
TCGA: ENSG00000142611
COSMIC: PRDM16

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000142611ENST00000270722Q9HAZ2
ENSG00000142611ENST00000378391Q9HAZ2
ENSG00000142611ENST00000463591U3KQL6
ENSG00000142611ENST00000509860H0YA13
ENSG00000142611ENST00000511072D6RDW0
ENSG00000142611ENST00000514189D6RFY3

Expression (GTEx)

0
5
10
15
20
25
30
35
40

Pathways

PathwaySourceExternal ID
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
PKMTs methylate histone lysinesREACTOMER-HSA-3214841

References

Pubmed IDYearTitleCitations
165829162006Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.404
196414922009Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.270
229396222012Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity.102
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
195675232009Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat.72
234543742013White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma.64
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
128168722003A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation.47
237685162013Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy.39
190499802009SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells.32

Citation

Jean-Loup Huret ; Sylvie Senon

PRDM16 (PR domain containing 16)

Atlas Genet Cytogenet Oncol Haematol. 2004-04-01

Online version: http://atlasgeneticsoncology.org/gene/408/prdm16