NUTM1 (nuclear protein in testis)

2007-02-01   Anna Collin 

Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

Identity

HGNC
LOCATION
15q14
LOCUSID
ALIAS
C15orf55,FAM22H,NUT
FUSION GENES

DNA/RNA

Description

The gene consists of 7 exons that span approximately 12 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon and the stop codon are predicted to exon 1 and exon 7, respectively.

Transcription

The corresponding "wildtype" mRNA transcript is 3.6 kb.

Proteins

Description

The open reading frame is predicted to encode an 1127 amino acid protein with an estimated molecular weight of 120 kDa.

Expression

Northern blot analysis has indicated that the normal expression of the NUT gene is highly restricted to the testis. No investigations have yet been made at the protein level.

Localisation

Nuclear.

Function

Unknown.

Implicated in

Entity name
Carcinoma with t(15;19)(q14;p13) translocation.
Prognosis
Carcinoma with t(15;19) translocation is invariably fatal with a rapid clinical course when located to the midline thoracic, head and neck structures. One tumor, displaying the cytogenetic and molecular cytogenetic features of carcinoma with t(15;19) translocation, but located to the iliac bone has been reported successfully cured.
It has been suggested that a critical prognostic difference exists between BRD4-NUT/t(15;19) positive tumors and tumors where NUT is rearranged but fused to an as yet unknown partner.
Cytogenetics
t(15;19)(q14;p13) [reported breakpoints: t(15;19)(q11-15;p13)].
Hybrid gene
The t(15;19)(q14;p13) results in an BRD4-NUT chimeric gene where exon 10 of BRD4 is fused to exon 2 of NUT.
Fusion protein
The BRD4-NUT fusion is composed of the N-terminal of BRD4 (amino acids 1-720 out of 1372) and almost the entire protein sequence of NUT (amino acids 6-1127). The N-terminal of BRD4 includes bromodomains 1 and 2 and other, less well characterized functional domains.
Oncogenesis
It has been suggested that the oncogenic effect of the NUT-BRD4 fusion is caused not only by the abnormal regulation of NUT by BRD4 promoter elements but also by the consequent ectopic expression of NUT in non-germinal tissues.

Breakpoints

Note

The vast majority of reported breakpoints in carcinoma with t(15;19) translocation were assigned to band 19p13, the exception being the cytogenetic interpretation of a 19q13 breakpoint reported once. The reported breakpoints on chromosome 15 have varied (15q11-q15).

Bibliography

Pubmed IDLast YearTitleAuthors
165424422006Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy.Engleson J et al
154830232004Midline carcinoma of children and young adults with NUT rearrangement.French CA et al
125437792003BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.French CA et al
17856731991Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19).Kees UR et al
164353792007Successful treatment of a child with t(15;19)-positive tumor.Mertens F et al

Other Information

Locus ID:

NCBI: 256646
MIM: 608963
HGNC: 29919
Ensembl: ENSG00000184507

Variants:

dbSNP: 256646
ClinVar: 256646
TCGA: ENSG00000184507
COSMIC: NUTM1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000184507ENST00000333756Q86Y26
ENSG00000184507ENST00000438749Q86Y26
ENSG00000184507ENST00000537011Q86Y26
ENSG00000184507ENST00000614490Q86Y26

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
179345172008BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells.118
206760582010Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains.63
248758582014NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism.50
262209942015The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within large topological domains.39
216527212011Perturbation of BRD4 protein function by BRD4-NUT protein abrogates cellular differentiation in NUT midline carcinoma.26
255123832015Mechanistic analysis of the role of bromodomain-containing protein 4 (BRD4) in BRD4-NUT oncoprotein-induced transcriptional activation.21
231283912013Novel BRD4-NUT fusion isoforms increase the pathogenic complexity in NUT midline carcinoma.16
159948772005Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro.15
297008872018CIC-NUTM1 fusion: A case which expands the spectrum of NUT-rearranged epithelioid malignancies.8
311457012019Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma.6

Citation

Anna Collin

NUTM1 (nuclear protein in testis)

Atlas Genet Cytogenet Oncol Haematol. 2007-02-01

Online version: http://atlasgeneticsoncology.org/gene/41595/nutm1