MEN1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- MEN1 (HGNC:7010) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- menin 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- No aliases found
- %HI
- 9.63(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.21(Read more about gnomAD LOEUF score)
- Cytoband
- 11q13
- Genomic Coordinates
-
GRCh37/hg19: chr11:64570986-64578766 NCBI Ensembl UCSC GRCh38/hg38: chr11:64803516-64811294 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001370259.2 ENST00000450708.7 (Read more about MANE Select)
- Function
- Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates ... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-1600
ClinGen Curation ID:
CCID:007453
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
01/12/2022
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- multiple endocrine neoplasia type 1 Monarch
HI Evidence:
-
PUBMED:
32780883
Kooblall KG, 2021. Reported a 5'UTR deletion in a MEN1 Family. The heterozygous 596bp deletion is between nucleotides -1087 and -492 upstream of the translation start site, located within the MEN1 5' untranslated region (UTR), and includes the core promoter and multiple cis-regulatory regions. The 596bp deletion resulted in significant reductions of 84% (p < 0.05) and 88% (p < 0.05) in MEN1 mRNA and menin protein, respectively, compared to unaffected individuals. Multiple types of tumors in family members having the deletion were identified: pituitary tumors, parathyroid tumors, lipoma; and angiofibroma.
-
PUBMED:
31044390
Kövesdi A, 2019. European study identified 27 MEN1 variants from a cohort of 189 consecutively enrolled probands and relatives. 22 variants were LOF (nonsense, splicing site, frameshift or intra-genic deletion) and 5 were missense variants (supplementary table).
-
PUBMED:
32430905
Mariathasan S., 2020 Described 2 patients having a frameshift variant without family history.
HI Evidence Comments:
MEN1 sequence level variants (nonsense, frameshift, splice site, and exonic deletions) as well as non-focal MEN1 whole gene deletions are associated with the development of Multiple Endocrine Neoplasia type 1 (MEN1) syndrome (PMID: 9510467, 15105049, and 21763627 and Genereviews). MEN1 syndrome is characterized by an increased susceptibility to develop endocrine tumors (i.e., parathryoid, pituitary, and well-differentiated endocrine tumors of the gastro-entero-pancreatic [GEP] tract), as well as non-endocrine tumors (e.g. facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas). The penetrance for the development of clinical features associated with MEN1 mutations is 50% by age 20 and 95% by age 40.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time there is no evidence to suggest triplosensitivity.
Genomic View
Select assembly:
(NC_000011.9)
(NC_000011.10)