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
PRDM16
LOCATION
1p36.32
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
63976
ALIAS
CMD1LL,KMT8F,LVNC8,MEL1,PFM13
FUSION GENES
Show Gene Fusions

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

Article 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
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

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

References

Pubmed IDYearTitleCitations
380726652024Discovery of PRDM16-Mediated TRPA1 Induction as the Mechanism for Low Tubulo-Interstitial Fibrosis in Diabetic Kidney Disease.1
380726652024Discovery of PRDM16-Mediated TRPA1 Induction as the Mechanism for Low Tubulo-Interstitial Fibrosis in Diabetic Kidney Disease.1
361749062023Novel association of SNP rs2297828 in PRDM16 gene with predisposition to type 2 diabetes.1
366392642023The ALDH2, IGSF9, and PRDM16 Proteins as Predictive Biomarkers for Prognosis in Breast Cancer.1
372116982023Androgen Receptor is a Negative Regulator of PRDM16 in Beige Adipocyte.2
373951362023PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.2
375747232023Distinct response of adipocyte progenitors to glucocorticoids determines visceral obesity via the TEAD1-miR-27b-PRDM16 axis.0
376024522023Long Noncoding RNA MAGI2-AS3 Represses Cell Progression in Clear Cell Renal Cell Carcinoma by Modulating the miR-629-5p/PRDM16 Axis.0
381132972023Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice.0
361749062023Novel association of SNP rs2297828 in PRDM16 gene with predisposition to type 2 diabetes.1
366392642023The ALDH2, IGSF9, and PRDM16 Proteins as Predictive Biomarkers for Prognosis in Breast Cancer.1
372116982023Androgen Receptor is a Negative Regulator of PRDM16 in Beige Adipocyte.2
373951362023PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.2
375747232023Distinct response of adipocyte progenitors to glucocorticoids determines visceral obesity via the TEAD1-miR-27b-PRDM16 axis.0
376024522023Long Noncoding RNA MAGI2-AS3 Represses Cell Progression in Clear Cell Renal Cell Carcinoma by Modulating the miR-629-5p/PRDM16 Axis.0

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-(pr-domain-containing-16)