MEN1
menin 1
Basic information
Region (hg38): 11:64803510-64811294
Links
Phenotypes
GenCC
Source:
- multiple endocrine neoplasia type 1 (Strong), mode of inheritance: AD
- multiple endocrine neoplasia type 1 (Supportive), mode of inheritance: AD
- pituitary gigantism (Supportive), mode of inheritance: AD
- familial isolated hyperparathyroidism (Supportive), mode of inheritance: AD
- multiple endocrine neoplasia type 1 (Limited), mode of inheritance: AD
- multiple endocrine neoplasia type 1 (Definitive), mode of inheritance: AD
- multiple endocrine neoplasia type 1 (Definitive), mode of inheritance: AD
- hereditary pheochromocytoma-paraganglioma (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Multiple endocrine neoplasia type I; Hyperparathyroidism, familial primary | AD | Endocrine; Oncologic | Surveillance and early detection of and treatment for neoplasms, as well as related sequelae may allow treatment (eg, with PPIs/somatostatin analogs, as well as appropriate and tailored surgical interventions and follow-up), and may decrease morbidity and mortality | Endocrine; Oncologic | 6108714; 2857681; 9215689; 9103196; 9236523; 9215690; 9463336; 9683585; 9554741; 9832038; 9506756; 9709923; 9792884; 10439966; 10193936; 11344233; 11739416; 11295574; 12417605; 12050235; 11836268; 12112656; 12791038; 15531478; 14871962; 15240620; 15292304; 14985373; 17879353; 20301710; 22522645; 22549346; 22581216; 22584706; 23052745; 23376981; 23443490; 23645327; 23652667; 23809488; 23919339; 23956349; 23961499; 24014011; 24037737; 24058102 |
ClinVar
This is a list of variants' phenotypes submitted to
- Multiple_endocrine_neoplasia,_type_1 (2215 variants)
- Hereditary_cancer-predisposing_syndrome (1539 variants)
- not_provided (371 variants)
- not_specified (97 variants)
- MEN1-related_disorder (62 variants)
- Hyperparathyroidism (27 variants)
- Multiple_endocrine_neoplasia (3 variants)
- Pituitary_adenoma_5,_multiple_types (3 variants)
- Hereditary_cancer (3 variants)
- Angiofibroma,_somatic (2 variants)
- Primary_hyperparathyroidism (2 variants)
- Parathyroid_gland_adenoma (2 variants)
- Hereditary_breast_ovarian_cancer_syndrome (2 variants)
- Somatotroph_adenoma (1 variants)
- Pituitary_dependent_hypercortisolism (1 variants)
- Medullary_thyroid_carcinoma (1 variants)
- Neuroblastoma (1 variants)
- Calcium_nephrolithiasis (1 variants)
- Hyperparathyroidism_1 (1 variants)
- Diabetes_mellitus (1 variants)
- Adrenocortical_adenoma (1 variants)
- Chronic_diarrhea (1 variants)
- Gastrointestinal_stromal_tumor (1 variants)
- Diffuse_midline_glioma,_H3_K27-altered (1 variants)
- Hypertensive_disorder (1 variants)
- Lung_carcinoid_tumor (1 variants)
- Gigantism (1 variants)
- Lipoma,_somatic (1 variants)
- Familial_isolated_hyperparathyroidism (1 variants)
- Pancreatic_insulin-producing_neuroendocrine_tumor (1 variants)
- Parathyroid_adenoma,_somatic (1 variants)
- Thyroid_adenoma (1 variants)
- Abnormal_circulating_calcium_concentration (1 variants)
- Ovarian_cancer (1 variants)
- Ependymoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MEN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001370259.2. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 13 | 623 | 32 | 674 | ||
| missense | 35 | 148 | 1068 | 83 | 1336 | |
| nonsense | 102 | 111 | ||||
| start loss | 4 | 3 | 7 | |||
| frameshift | 254 | 42 | 305 | |||
| splice donor/acceptor (+/-2bp) | 40 | 23 | 68 | |||
| Total | 438 | 228 | 1094 | 707 | 34 |
Highest pathogenic variant AF is 0.00024173524
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MEN1 | protein_coding | protein_coding | ENST00000337652 | 9 | 7785 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000288 | 125672 | 0 | 2 | 125674 | 0.00000796 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.25 | 200 | 378 | 0.530 | 0.0000241 | 3907 |
| Missense in Polyphen | 50 | 159.08 | 0.31431 | 1640 | ||
| Synonymous | 0.754 | 153 | 165 | 0.925 | 0.0000106 | 1301 |
| Loss of Function | 4.71 | 1 | 27.8 | 0.0360 | 0.00000147 | 290 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000181 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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 HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity). May be involved in DNA repair. {ECO:0000250, ECO:0000269|PubMed:11274402, ECO:0000269|PubMed:11526476, ECO:0000269|PubMed:12837246, ECO:0000269|PubMed:12874027, ECO:0000269|PubMed:14992727}.;
- Disease
- DISEASE: Note=MEN1 inactivating mutations are responsible for hyperfunctioning of the parathyroid glands and subsequent primary hyperparathyroidism. Primary hyperparathyroidism can occur in isolation or in association with multiple endocrine neoplasia. {ECO:0000269|PubMed:10634381, ECO:0000269|PubMed:10664521, ECO:0000269|PubMed:12016470, ECO:0000269|PubMed:12699448, ECO:0000269|PubMed:9792884, ECO:0000269|PubMed:9843042, ECO:0000269|PubMed:9888389}.;
- Pathway
- Cushing,s syndrome - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Cell Cycle;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);RHO GTPases activate IQGAPs;RHO GTPase Effectors;Signaling by Rho GTPases;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT
(Consensus)
Intolerance Scores
- loftool
- rvis_EVS
- -0.27
- rvis_percentile_EVS
- 34.6
Haploinsufficiency Scores
- pHI
- 0.513
- hipred
- Y
- hipred_score
- 0.771
- ghis
- 0.561
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Men1
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; liver/biliary system phenotype; immune system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; neoplasm; embryo phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;MAPK cascade;mitotic cell cycle;negative regulation of protein phosphorylation;osteoblast development;type B pancreatic cell differentiation;DNA repair;cellular response to DNA damage stimulus;brain development;negative regulation of cell population proliferation;response to UV;response to gamma radiation;negative regulation of cell-substrate adhesion;positive regulation of transforming growth factor beta receptor signaling pathway;positive regulation of protein binding;regulation of activin receptor signaling pathway;histone lysine methylation;negative regulation of DNA-binding transcription factor activity;post-translational protein modification;cellular protein metabolic process;negative regulation of osteoblast differentiation;negative regulation of cyclin-dependent protein serine/threonine kinase activity;negative regulation of cell cycle;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of JNK cascade;decidualization;negative regulation of epithelial cell proliferation;negative regulation of telomerase activity;regulation of type B pancreatic cell proliferation;cellular response to glucose stimulus;cellular response to peptide hormone stimulus;response to transforming growth factor beta;negative regulation of cell cycle G1/S phase transition;beta-catenin-TCF complex assembly
- Cellular component
- nuclear chromosome, telomeric region;chromatin;nuclear chromatin;nucleus;nucleoplasm;cytoplasm;endoplasmic reticulum lumen;cytosol;nuclear matrix;cleavage furrow;protein-containing complex;histone methyltransferase complex
- Molecular function
- four-way junction DNA binding;Y-form DNA binding;chromatin binding;double-stranded DNA binding;protein binding;histone-lysine N-methyltransferase activity;protein binding, bridging;transcription regulatory region DNA binding;protein N-terminus binding;R-SMAD binding