Details of Disease

Disease Name

Multiple endocrine neoplasia type 1

MEA 1; endocrine adenomatosis multiple; multiple endocrine neoplasia, type 1; MEN1 somatic mutations; endocrine adenomatosis, multiple; multiple endocrine adenomatosis; Wermer's syndrome; multiple endocrine adenomatosis, type I; multiple endocrine neoplasia caused by mutation in MEN1; multiple endocrine neoplasia, type I; multiple endocrine adenomatosis type 1; MEA type 1; MEA type I; men 1; multiple endocrine neoplasia type I; MEN1 syndrome; MEN1; multiple endocrine neoplasia 1; men type I; multiple endocrine neoplasia type 1; Wermer syndrome; multiple endocrine adenomatosis type I; men type 1; MEN1 multiple endocrine neoplasia; multiple endocrine neoplasia type 1 syndrome

Definition

Multiple endocrine neoplasia Type 1 (MEN1) is a frequent form of MEN, a rare inherited cancer syndrome, characterized by the development of neuroendocrine tumors of the parathyroid, pancreas, and anterior pituitary gland, and less commonly the adrenal cortical gland, with other non-endocrine tumors in some patients.

Disease Hierarchy

DISFK7RF: Adrenal gland neoplasm

DIS6NA55: Familial primary hyperparathyroidism

DIS3HIWD: Autosomal dominant disease

DISZGBKW: Multiple endocrine neoplasia

DIS0RJRK: Multiple endocrine neoplasia type 1

Disease Identifiers

MONDO ID

MONDO_0007540

MESH ID

D018761

UMLS CUI

C0025267

OMIM ID

131100

MedGen ID

9957

Orphanet ID

652

SNOMED CT ID

30664006

General Information of Disease (ID: DIS0RJRK)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDKN1A	TT9GUW0	Limited	Genetic Variation	[1]
AMHR2	TTZDCPK	Strong	Biomarker	[2]
CAPN1	TT1WBIJ	Strong	Genetic Variation	[3]
CDKN2C	TTBRUGA	Strong	Altered Expression	[4]
PDE11A	TTTWC79	Strong	Genetic Variation	[5]
PPP1CA	TTFLH0E	Strong	Biomarker	[6]
PYGM	TTZHY6R	Strong	Genetic Variation	[7]
RET	TT4DXQT	Strong	Genetic Variation	[8]
SDHD	TTVH9W8	Strong	Biomarker	[9]
SST	TTWF7UG	Strong	Biomarker	[10]
SUV39H1	TTUWQTK	Strong	Genetic Variation	[11]
ELK3	TT5OJMV	Definitive	Biomarker	[12]
EPHB1	TT8MDAC	Definitive	Biomarker	[12]
PPY	TTIB95A	Definitive	Biomarker	[13]
SLC6A2	TTAWNKZ	Definitive	Biomarker	[12]
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⏷ Show the Full List of 15 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC29A2	DTW78DQ	Strong	Genetic Variation	[14]
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This Disease Is Related to 39 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CALB1	OTM7IXDG	Strong	Genetic Variation	[15]
CDC73	OT6JASZ1	Strong	Genetic Variation	[16]
CDCA7L	OT1FFWKC	Strong	Biomarker	[17]
CDKN2B	OTAG24N1	Strong	Biomarker	[18]
CDKN3	OTBE3H07	Strong	Genetic Variation	[19]
CHST4	OTESMIW5	Strong	Biomarker	[6]
DAXX	OTX6O7PL	Strong	Genetic Variation	[20]
DEPDC5	OTE70JLY	Strong	Genetic Variation	[20]
EIF4EBP3	OTYY2WS5	Strong	Biomarker	[21]
FKBP2	OTHBZHX0	Strong	Biomarker	[22]
FOXN3	OTOJYJZP	Strong	Genetic Variation	[23]
GCM2	OTSKNPTI	Strong	Biomarker	[24]
GHRH	OT94U6MO	Strong	Biomarker	[25]
GNA12	OT3IRZH3	Strong	Biomarker	[26]
MFHAS1	OTS922CJ	Strong	Genetic Variation	[27]
NEUROG3	OT6DIPWC	Strong	Altered Expression	[28]
PDE8B	OT4217NK	Strong	Genetic Variation	[5]
POU3F2	OT30NFOC	Strong	Altered Expression	[29]
PPP2R5B	OTW2QIX9	Strong	Biomarker	[30]
RASSF7	OT0V4EIZ	Strong	Genetic Variation	[31]
RBM47	OT6W67VM	Strong	Biomarker	[17]
RIT2	OTSNYG0D	Strong	Biomarker	[32]
RPA2	OTZ54WAF	Strong	Biomarker	[33]
SCG2	OTXWUQQL	Strong	Genetic Variation	[34]
SDHA	OTOJ8QFF	Strong	Genetic Variation	[9]
SDHB	OTRE1M1T	Strong	Genetic Variation	[9]
SDHC	OTC8G2MX	Strong	Biomarker	[5]
SIPA1	OTXY5RXC	Strong	Biomarker	[35]
TCHP	OTVDMHSY	Strong	Genetic Variation	[36]
CIB1	OT4BVCRU	Definitive	Altered Expression	[4]
DCTN6	OTI8PIN9	Definitive	Genetic Variation	[37]
FGF3	OT9PK2SI	Definitive	Biomarker	[38]
IFI27	OTI2XGIT	Definitive	Genetic Variation	[37]
INTS2	OT2N5TCK	Definitive	Biomarker	[38]
MEN1	OTN6U6V0	Definitive	Autosomal dominant	[39]
PSMD9	OT6Y5CC3	Definitive	Genetic Variation	[37]
SF1	OTLEDM2S	Definitive	Genetic Variation	[40]
TICAM2	OTK7GIJ5	Definitive	Genetic Variation	[37]
TMED7	OTONO8E6	Definitive	Genetic Variation	[37]
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⏷ Show the Full List of 39 DOT(s)

References

1	Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states.J Clin Endocrinol Metab. 2009 May;94(5):1826-34. doi: 10.1210/jc.2008-2083. Epub 2009 Jan 13.
2	Deregulation of anti-Mullerian hormone/BMP and transforming growth factor-beta pathways in Leydig cell lesions developed in male heterozygous multiple endocrine neoplasia type 1 mutant mice.Endocr Relat Cancer. 2008 Mar;15(1):217-27. doi: 10.1677/ERC-06-0046.
3	A 500-kb sequence-ready cosmid contig and transcript map of the MEN1 region on 11q13.Genomics. 1999 Jan 1;55(1):49-56. doi: 10.1006/geno.1998.5625.
4	Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor.Endocr J. 2011;58(4):287-96. doi: 10.1507/endocrj.k10e-158. Epub 2011 Mar 25.
5	Multiple endocrine neoplasias: advances and challenges for the future.J Intern Med. 2009 Jul;266(1):1-4. doi: 10.1111/j.1365-2796.2009.02108.x.
6	A radiation hybrid map of the proximal long arm of human chromosome 11 containing the multiple endocrine neoplasia type 1 (MEN-1) and bcl-1 disease loci.Am J Hum Genet. 1991 Dec;49(6):1189-96.
7	Somatic mutations in MEN type 1 tumors, consistent with the Knudson "two-hit" hypothesis.J Clin Endocrinol Metab. 2001 Sep;86(9):4371-4. doi: 10.1210/jcem.86.9.7844.
8	Primary Hyperparathyroidism.Front Horm Res. 2019;51:1-12. doi: 10.1159/000491034. Epub 2018 Nov 19.
9	Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.J Clin Endocrinol Metab. 2015 Mar;100(3):E531-41. doi: 10.1210/jc.2014-3399. Epub 2014 Dec 12.
10	Chemoprevention with Somatuline Delays the Progression of Pancreatic Neuroendocrine Neoplasms in a Mouse Model of Multiple Endocrine Neoplasia Type 1 (MEN1).World J Surg. 2019 Mar;43(3):831-838. doi: 10.1007/s00268-018-4839-8.
11	Menin mediates epigenetic regulation via histone H3 lysine 9 methylation.Cell Death Dis. 2013 Apr 11;4(4):e583. doi: 10.1038/cddis.2013.98.
12	Pancreatic neuroendocrine tumors in MEN1 disease: a mono-centric longitudinal and prognostic study.Endocrine. 2018 May;60(2):362-367. doi: 10.1007/s12020-017-1327-0. Epub 2017 May 31.
13	Genetic screening for MEN1 mutations in families presenting with familial primary hyperparathyroidism.World J Surg. 2002 Aug;26(8):907-13. doi: 10.1007/s00268-002-6617-9. Epub 2002 May 21.
14	The human HNP36 gene is localized to chromosome 11q13 and produces alternative transcripts that are not mutated in multiple endocrine neoplasia, type 1 (MEN I) syndrome.Genomics. 1997 Jun 1;42(2):325-30. doi: 10.1006/geno.1997.4751.
15	Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I. Studies in four families.J Clin Endocrinol Metab. 1992 Sep;75(3):846-51. doi: 10.1210/jcem.75.3.1517376.
16	Mutational and large deletion study of genes implicated in hereditary forms of primary hyperparathyroidism and correlation with clinical features.PLoS One. 2017 Oct 16;12(10):e0186485. doi: 10.1371/journal.pone.0186485. eCollection 2017.
17	Distinct genome-wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors.Cancer. 2019 Apr 15;125(8):1247-1257. doi: 10.1002/cncr.31930. Epub 2019 Jan 8.
18	Caspase 8 and menin expressions are not correlated in human parathyroid tumors.Endocr J. 2010;57(9):825-32. doi: 10.1507/endocrj.k10e-085. Epub 2010 Jul 3.
19	Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4).Mol Cell Endocrinol. 2014 Apr 5;386(1-2):2-15. doi: 10.1016/j.mce.2013.08.002. Epub 2013 Aug 8.
20	Loss of Chromatin-Remodeling Proteins and/or CDKN2A Associates With Metastasis of Pancreatic Neuroendocrine Tumors and Reduced Patient Survival Times.Gastroenterology. 2018 Jun;154(8):2060-2063.e8. doi: 10.1053/j.gastro.2018.02.026. Epub 2018 Mar 2.
21	The EIF4EBP3 translational repressor is a marker of CDC73 tumor suppressor haploinsufficiency in a parathyroid cancer syndrome.Cell Death Dis. 2012 Feb 2;3(2):266. doi: 10.1038/cddis.2012.6.
22	Exclusion of the 13-kDa rapamycin binding protein gene (FKBP2) as a candidate gene for multiple endocrine neoplasia type 1.Hum Genet. 1995 Apr;95(4):455-8. doi: 10.1007/BF00208976.
23	Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain.J Clin Endocrinol Metab. 2014 Nov;99(11):E2387-91. doi: 10.1210/jc.2013-4432. Epub 2014 Sep 11.
24	Recent Topics Around Multiple Endocrine Neoplasia Type 1.J Clin Endocrinol Metab. 2018 Apr 1;103(4):1296-1301. doi: 10.1210/jc.2017-02340.
25	Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype.Eur J Gastroenterol Hepatol. 2013 Jul;25(7):858-62. doi: 10.1097/MEG.0b013e32835f433f.
26	Natural History of MEN1 GEP-NET: Single-Center Experience After a Long Follow-Up.World J Surg. 2017 Sep;41(9):2312-2323. doi: 10.1007/s00268-017-4019-2.
27	DNA hypermethylation profiles in squamous cell carcinoma of the vulva.Int J Gynecol Pathol. 2009 Jan;28(1):63-75. doi: 10.1097/PGP.0b013e31817d9c61.
28	Neurogenin 3 and neurogenic differentiation 1 are retained in the cytoplasm of multiple endocrine neoplasia type 1 islet and pancreatic endocrine tumor cells.Pancreas. 2009 Apr;38(3):259-66. doi: 10.1097/MPA.0b013e3181930818.
29	Expression of developing neural transcription factors in lung carcinoid tumors.Pathol Int. 2014 Aug;64(8):365-74. doi: 10.1111/pin.12183.
30	Mapping of the gene encoding the B56 beta subunit of protein phosphatase 2A (PPP2R5B) to a 0.5-Mb region of chromosome 11q13 and its exclusion as a candidate gene for multiple endocrine neoplasia type 1 (MEN1).Hum Genet. 1997 Sep;100(3-4):481-5. doi: 10.1007/s004390050538.
31	Loss of the same alleles of HRAS1 and D11S151 in two independent pancreatic cancers from a patient with multiple endocrine neoplasia type 1.Cancer Res. 1989 May 15;49(10):2716-21.
32	O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) uptake in insulinoma: first results from a xenograft mouse model and from human.Nucl Med Biol. 2017 Oct;53:21-28. doi: 10.1016/j.nucmedbio.2017.07.005. Epub 2017 Jul 12.
33	Upregulation of RPA2 promotes NF-B activation in breast cancer by relieving the antagonistic function of menin on NF-B-regulated transcription.Carcinogenesis. 2017 Feb 1;38(2):196-206. doi: 10.1093/carcin/bgw123.
34	The search for the MEN1 gene. The European Consortium on MEN-1.J Intern Med. 1998 Jun;243(6):441-6. doi: 10.1046/j.1365-2796.1998.00347.x.
35	Genomic organization and cloning of the human homologue of murine Sipa-1.Gene. 1998 Jul 3;214(1-2):215-21. doi: 10.1016/s0378-1119(98)00212-1.
36	A new double substitution mutation in the MEN1 gene: a limited penetrance and a specific phenotype.Eur J Hum Genet. 2013 Jun;21(6):695-7. doi: 10.1038/ejhg.2012.241. Epub 2012 Nov 28.
37	Hyperparathyroid genes: sequences reveal answers and questions.Endocr Pract. 2011 Jul-Aug;17 Suppl 3(Suppl 3):18-27. doi: 10.4158/EP11067.RA.
38	Linkage analysis of 7 polymorphic markers at chromosome 11p11.2-11q13 in 27 multiple endocrine neoplasia type 1 families.Ann Hum Genet. 1993 Jan;57(1):17-25. doi: 10.1111/j.1469-1809.1993.tb00883.x.
39	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
40	Diverse modes of alternative splicing of human splicing factor SF1 deduced from the exon-intron structure of the gene.Gene. 1998 Apr 28;211(1):29-37. doi: 10.1016/s0378-1119(98)00058-4.