MCID: MLT086
MIFTS: 50

Multiple Endocrine Neoplasia, Type Iv

Categories: Genetic diseases, Endocrine diseases, Rare diseases, Gastrointestinal diseases, Cancer diseases, Neuronal diseases

Aliases & Classifications for Multiple Endocrine Neoplasia, Type Iv

MalaCards integrated aliases for Multiple Endocrine Neoplasia, Type Iv:

Name: Multiple Endocrine Neoplasia, Type Iv 54 12 13 69
Multiple Endocrine Neoplasia Type 4 12 24 56 14
Men4 24 56 71
Multiple Endocrine Neoplasia Type Iv 24
Multiple Endocrine Neoplasia, Type 4 29
Multiple Endocrine Neoplasia 4 71
Men 4 24

Characteristics:

Orphanet epidemiological data:

56
multiple endocrine neoplasia type 4
Inheritance: Autosomal dominant,Not applicable;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
variable manifestations
onset of tumors usually in adulthood


HPO:

32
multiple endocrine neoplasia, type iv:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 56  
Rare endocrine diseases


Summaries for Multiple Endocrine Neoplasia, Type Iv

UniProtKB/Swiss-Prot : 71 Multiple endocrine neoplasia 4: Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.

MalaCards based summary : Multiple Endocrine Neoplasia, Type Iv, also known as multiple endocrine neoplasia type 4, is related to familial myelofibrosis and extraskeletal ewing sarcoma, and has symptoms including diarrhea, hyperinsulinemic hypoglycemia and hyperparathyroidism. An important gene associated with Multiple Endocrine Neoplasia, Type Iv is CDKN1B (Cyclin Dependent Kinase Inhibitor 1B), and among its related pathways/superpathways are Mitotic G1-G1/S phases and DNA Damage. The drugs Dutasteride and Methyltestosterone have been mentioned in the context of this disorder. Affiliated tissues include thyroid, pituitary and pancreas, and related phenotypes are Increased shRNA abundance (Z-score > 2) and endocrine/exocrine gland

Description from OMIM: 610755

Related Diseases for Multiple Endocrine Neoplasia, Type Iv

Diseases in the Multiple Endocrine Neoplasia family:

Multiple Endocrine Neoplasia Iia Multiple Endocrine Neoplasia Iib
Multiple Endocrine Neoplasia 1 Multiple Endocrine Neoplasia, Type Iv

Diseases related to Multiple Endocrine Neoplasia, Type Iv via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
id Related Disease Score Top Affiliating Genes
1 familial myelofibrosis 10.4 AIP CDKN1B
2 extraskeletal ewing sarcoma 10.4 AIP MEN1
3 didymosis aplasticosebacea 10.4 AIP MEN1
4 vertebral artery occlusion 10.2 AIP PRL
5 glassy cell carcinoma of the cervix 10.2 AIP PRL
6 protein s deficiency 10.2 AIP PRL
7 skin benign neoplasm 10.2 MEN1 PRKAR1A
8 pituitary adenoma, prolactin-secreting 10.2 AIP PRL
9 psychogenic movement 10.1 MEN1 PRL
10 cold-induced sweating syndrome 2 10.1 AIP PRL
11 trabecular follicular adenocarcinoma 10.1 PRKAR1A PRL
12 bronchiectasis 10.1 PRKAR1A PRL
13 uterine ligament clear cell adenocarcinoma 10.0 MEN1 PRL
14 multiple endocrine neoplasia 10.0
15 adrenal cortex disease 9.9 PRKAR1A PRL
16 sporadic hemiplegic migraine 9.9 CDKN1B MEN1 PRKAR1A
17 hyperparathyroidism, familial primary 9.9 CDKN1B MEN1 PRKAR1A
18 subserous uterine fibroid 9.9 CDKN1B MEN1 PRKAR1A
19 mononeuritis of upper limb and mononeuritis multiplex 9.9 AIP MEN1 PRKAR1A
20 unilateral retinoblastoma 9.9 CDK2 CDKN1B
21 strabismus 9.9 AIP MEN1 PRL
22 cardiovascular organ benign neoplasm 9.8 AIP MEN1 PRL
23 vestibular gland benign neoplasm 9.8 AIP MEN1 PRL
24 male reproductive organ benign neoplasm 9.8 AIP MEN1 PRL
25 pharynx cancer 9.8 CDK2 CDKN1B
26 thrombophilia 9.8 AIP MEN1 PRL
27 osseous heteroplasia, progressive 9.8 MEN1 PRKAR1A PRL
28 childhood optic nerve glioma 9.8 AIP MEN1 PRL
29 parathyroid oncocytic adenoma 9.7 CDKN2C MEN1
30 post-surgical hypoinsulinemia 9.7 CDK2 CDKN1B
31 small cell sarcoma 9.7 CDK2 CDKN1B
32 lymphoplasmacytic lymphoma 9.6 MEN1 PRKAR1A
33 ataxia-oculomotor apraxia 3 9.5 AIP CDKN1B MEN1 PRKAR1A
34 pituitary adenoma, acth-secreting 9.3 AIP MEN1 PRKAR1A PRL
35 usher syndrome, type 1f 9.3 AIP MEN1 PRKAR1A PRL
36 immunodeficiency, common variable, 5 8.8 CDKN1B CDKN2C MEN1 PRKAR1A PRL
37 sifrim-hitz-weiss syndrome 7.5 AIP CDK2 CDKN1B CDKN2C MEN1 PRKAR1A

Graphical network of the top 20 diseases related to Multiple Endocrine Neoplasia, Type Iv:



Diseases related to Multiple Endocrine Neoplasia, Type Iv

Symptoms & Phenotypes for Multiple Endocrine Neoplasia, Type Iv

Symptoms via clinical synopsis from OMIM:

54

Endocrine Features:
parathyroid adenoma
pituitary adenoma
acromegaly
carcinoid tumors

Genitourinary- Kidneys:
renal angiomyolipoma

Respiratory- Airways:
bronchial carcinoid

Neoplasia:
pancreatic endocrine neoplasia
papillary thyroid cancer
neuroendocrine cervical carcinoma


Clinical features from OMIM:

610755

Human phenotypes related to Multiple Endocrine Neoplasia, Type Iv:

56 32 (show all 40)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 diarrhea 56 32 frequent (33%) Frequent (79-30%) HP:0002014
2 hyperinsulinemic hypoglycemia 56 32 frequent (33%) Frequent (79-30%) HP:0000825
3 hyperparathyroidism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000843
4 hypercalcemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0003072
5 erythema 56 32 occasional (7.5%) Occasional (29-5%) HP:0010783
6 thyroid adenoma 56 32 frequent (33%) Frequent (79-30%) HP:0000854
7 episodic abdominal pain 56 32 frequent (33%) Frequent (79-30%) HP:0002574
8 parathyroid adenoma 56 32 hallmark (90%) Very frequent (99-80%) HP:0002897
9 parathyroid hyperplasia 56 32 hallmark (90%) Very frequent (99-80%) HP:0008208
10 pituitary adenoma 56 32 Frequent (79-30%) HP:0002893
11 zollinger-ellison syndrome 56 32 frequent (33%) Frequent (79-30%) HP:0002044
12 esophagitis 56 32 frequent (33%) Frequent (79-30%) HP:0100633
13 confetti-like hypopigmented macules 56 32 occasional (7.5%) Occasional (29-5%) HP:0007449
14 insulinoma 56 32 frequent (33%) Frequent (79-30%) HP:0012197
15 renal angiomyolipoma 56 32 frequent (33%) Frequent (79-30%) HP:0006772
16 peptic ulcer 56 32 frequent (33%) Frequent (79-30%) HP:0004398
17 thymoma 56 32 very rare (1%) Very rare (<4-1%) HP:0100522
18 extrahepatic cholestasis 56 32 occasional (7.5%) Occasional (29-5%) HP:0012334
19 increased glucagon level 56 32 occasional (7.5%) Occasional (29-5%) HP:0030688
20 carcinoid tumor 56 32 Occasional (29-5%) HP:0100570
21 elevated circulating parathyroid hormone level 56 32 hallmark (90%) Very frequent (99-80%) HP:0003165
22 growth hormone excess 56 32 frequent (33%) Frequent (79-30%) HP:0000845
23 subcutaneous lipoma 56 32 frequent (33%) Frequent (79-30%) HP:0001031
24 pituitary prolactin cell adenoma 56 32 frequent (33%) Frequent (79-30%) HP:0006767
25 adrenocortical adenoma 56 32 frequent (33%) Frequent (79-30%) HP:0008256
26 fasting hyperinsulinemia 56 32 frequent (33%) Frequent (79-30%) HP:0008283
27 angiofibromas 56 32 frequent (33%) Frequent (79-30%) HP:0010615
28 pituitary growth hormone cell adenoma 56 32 frequent (33%) Frequent (79-30%) HP:0011760
29 pituitary null cell adenoma 56 32 frequent (33%) Frequent (79-30%) HP:0011761
30 pituitary corticotropic cell adenoma 56 32 occasional (7.5%) Occasional (29-5%) HP:0008291
31 increased urinary cortisol level 56 32 occasional (7.5%) Occasional (29-5%) HP:0012030
32 cervix cancer 56 32 occasional (7.5%) Occasional (29-5%) HP:0030079
33 testicular neoplasm 56 32 occasional (7.5%) Occasional (29-5%) HP:0010788
34 pulmonary carcinoid tumor 56 32 frequent (33%) Frequent (79-30%) HP:0030445
35 parathyroid carcinoma 56 32 occasional (7.5%) Occasional (29-5%) HP:0006780
36 abnormality of the endocrine system 56 Very frequent (99-80%)
37 neuroendocrine neoplasm 56 Frequent (79-30%)
38 abnormality of pancreas physiology 56 Frequent (79-30%)
39 hypercortisolism 56 Occasional (29-5%)
40 increased circulating cortisol level 32 occasional (7.5%) HP:0003118

GenomeRNAi Phenotypes related to Multiple Endocrine Neoplasia, Type Iv according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.74 PRKAR1A
2 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.74 MEN1
3 Increased shRNA abundance (Z-score > 2) GR00366-A-118 9.74 CDK2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-122 9.74 PRKAR1A CDK2 MEN1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-128 9.74 MEN1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-13 9.74 CDK2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.74 CDK2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.74 PRKAR1A
9 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.74 PRKAR1A
10 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.74 MEN1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-189 9.74 PRKAR1A
12 Increased shRNA abundance (Z-score > 2) GR00366-A-205 9.74 PRKAR1A
13 Increased shRNA abundance (Z-score > 2) GR00366-A-25 9.74 CDK2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-39 9.74 PRKAR1A
15 Increased shRNA abundance (Z-score > 2) GR00366-A-41 9.74 CDK2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.74 CDK2 MEN1
17 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.74 MEN1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.74 MEN1 CDK2
19 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.74 PRKAR1A
20 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.74 CDK2
21 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.74 MEN1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.74 CDK2

MGI Mouse Phenotypes related to Multiple Endocrine Neoplasia, Type Iv:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.98 PRL AIP CDK2 CDKN1B CDKN2C MEN1
2 cardiovascular system MP:0005385 9.95 MEN1 PRKAR1A AIP CDK2 CDKN1B CDKN2C
3 cellular MP:0005384 9.93 AIP CDK2 CDKN1B CDKN2C MEN1 PRKAR1A
4 homeostasis/metabolism MP:0005376 9.91 AIP CDK2 CDKN1B CDKN2C MEN1 PRKAR1A
5 growth/size/body region MP:0005378 9.88 AIP CDK2 CDKN1B CDKN2C MEN1 PRKAR1A
6 immune system MP:0005387 9.8 CDK2 CDKN1B CDKN2C MEN1 PRKAR1A PRL
7 integument MP:0010771 9.65 AIP CDK2 CDKN1B CDKN2C PRL
8 liver/biliary system MP:0005370 9.63 AIP CDK2 CDKN1B MEN1 PRKAR1A PRL
9 neoplasm MP:0002006 9.5 AIP CDK2 CDKN1B CDKN2C MEN1 PRKAR1A
10 reproductive system MP:0005389 9.1 CDK2 CDKN1B CDKN2C MEN1 PRKAR1A PRL

Drugs & Therapeutics for Multiple Endocrine Neoplasia, Type Iv

Drugs for Multiple Endocrine Neoplasia, Type Iv (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dutasteride Approved, Investigational Phase 1, Phase 2 164656-23-9 152945 6918296
2
Methyltestosterone Approved Phase 1, Phase 2 58-18-4 6010
3
Testosterone Approved, Investigational Phase 1, Phase 2 58-22-0 6013
4 5-alpha Reductase Inhibitors Phase 1, Phase 2
5 Anabolic Agents Phase 1, Phase 2
6 Androgens Phase 1, Phase 2
7 Antineoplastic Agents, Hormonal Phase 1, Phase 2
8 Contraceptive Agents Phase 1, Phase 2
9 Hormone Antagonists Phase 1, Phase 2
10 Hormones Phase 1, Phase 2
11 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 1, Phase 2
12 Steroid Synthesis Inhibitors Phase 1, Phase 2
13 Testosterone 17 beta-cypionate Phase 1, Phase 2
14
Testosterone enanthate Phase 1, Phase 2 315-37-7 9416
15 Testosterone undecanoate Phase 1, Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Ejaculatory Sparing vs. Non-ejaculatory Sparing GreenLight Laser Photoselective Vaporization of the Prostate Recruiting NCT02749604 Phase 4
2 Oral Androgens in Man-4: (Short Title: Oral T-4) Completed NCT00399165 Phase 1, Phase 2 Testosterone Enanthate;Testosterone Enanthate;Dutasteride;Dutasteride
3 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Multiple Endocrine Neoplasia, Type Iv

Genetic Tests for Multiple Endocrine Neoplasia, Type Iv

Genetic tests related to Multiple Endocrine Neoplasia, Type Iv:

id Genetic test Affiliating Genes
1 Multiple Endocrine Neoplasia, Type 4 29
2 Multiple Endocrine Neoplasia Type 4 24 CDKN1B

Anatomical Context for Multiple Endocrine Neoplasia, Type Iv

MalaCards organs/tissues related to Multiple Endocrine Neoplasia, Type Iv:

39
Thyroid, Pituitary, Pancreas, Prostate, Cervix

Publications for Multiple Endocrine Neoplasia, Type Iv

Variations for Multiple Endocrine Neoplasia, Type Iv

ClinVar genetic disease variations for Multiple Endocrine Neoplasia, Type Iv:

6 (show all 19)
id Gene Variation Type Significance SNP ID Assembly Location
1 CDKN1B NM_004064.4(CDKN1B): c.227G> A (p.Trp76Ter) single nucleotide variant Pathogenic rs121917832 GRCh37 Chromosome 12, 12871000: 12871000
2 RET NM_020975.4(RET): c.1901G> A (p.Cys634Tyr) single nucleotide variant Pathogenic/Likely pathogenic rs75996173 GRCh37 Chromosome 10, 43609949: 43609949
3 RET NM_020630.4(RET): c.1859G> A (p.Cys620Tyr) single nucleotide variant Pathogenic/Likely pathogenic rs77503355 GRCh37 Chromosome 10, 43609103: 43609103
4 RET NM_020975.4(RET): c.1900T> C (p.Cys634Arg) single nucleotide variant Pathogenic/Likely pathogenic rs75076352 GRCh37 Chromosome 10, 43609948: 43609948
5 RET NM_020630.4(RET): c.1902C> G (p.Cys634Trp) single nucleotide variant Pathogenic/Likely pathogenic rs77709286 GRCh37 Chromosome 10, 43609950: 43609950
6 RET NM_020975.4(RET): c.2753T> C (p.Met918Thr) single nucleotide variant Pathogenic/Likely pathogenic rs74799832 GRCh37 Chromosome 10, 43617416: 43617416
7 RET NM_020630.4(RET): c.1852T> C (p.Cys618Arg) single nucleotide variant Pathogenic/Likely pathogenic rs76262710 GRCh37 Chromosome 10, 43609096: 43609096
8 RET NM_020630.4(RET): c.2304G> C (p.Glu768Asp) single nucleotide variant Pathogenic/Likely pathogenic rs78014899 GRCh37 Chromosome 10, 43613840: 43613840
9 RET NM_020975.4(RET): c.1826G> A (p.Cys609Tyr) single nucleotide variant Pathogenic/Likely pathogenic rs77939446 GRCh37 Chromosome 10, 43609070: 43609070
10 RET NM_020975.4(RET): c.2671T> G (p.Ser891Ala) single nucleotide variant Pathogenic/Likely pathogenic rs75234356 GRCh37 Chromosome 10, 43615592: 43615592
11 RET NM_020975.4(RET): c.1853G> A (p.Cys618Tyr) single nucleotide variant Pathogenic/Likely pathogenic rs79781594 GRCh37 Chromosome 10, 43609097: 43609097
12 RET NM_020630.4(RET): c.1888T> C (p.Cys630Arg) single nucleotide variant Pathogenic/Likely pathogenic rs377767404 GRCh37 Chromosome 10, 43609936: 43609936
13 RET NM_020630.4(RET): c.2410G> C (p.Val804Leu) single nucleotide variant Pathogenic/Likely pathogenic rs79658334 GRCh37 Chromosome 10, 43614996: 43614996
14 RET NM_020975.4(RET): c.2647_2648delGCinsTT (p.Ala883Phe) indel Pathogenic/Likely pathogenic rs377767429 GRCh37 Chromosome 10, 43615568: 43615569
15 CDKN1B NM_004064.4(CDKN1B): c.59_77dup19 (p.Ser27Glyfs) duplication Pathogenic rs786201007 GRCh38 Chromosome 12, 12717898: 12717916
16 CDKN1B NM_004064.4(CDKN1B): c.206C> T (p.Pro69Leu) single nucleotide variant Pathogenic rs777354267 GRCh37 Chromosome 12, 12870979: 12870979
17 CDKN1B NM_004064.4(CDKN1B): c.-456_-453delCCTT deletion Pathogenic rs786201010 GRCh37 Chromosome 12, 12870318: 12870321
18 CDKN1B NM_004064.4(CDKN1B): c.374_375delCT (p.Ser125Terfs) deletion Pathogenic rs786201011 GRCh37 Chromosome 12, 12871147: 12871148
19 CDKN1B NM_004064.4(CDKN1B): c.49_52delGACG (p.Asp17Profs) deletion Pathogenic rs1060500186 GRCh38 Chromosome 12, 12717888: 12717891

Expression for Multiple Endocrine Neoplasia, Type Iv

Search GEO for disease gene expression data for Multiple Endocrine Neoplasia, Type Iv.

Pathways for Multiple Endocrine Neoplasia, Type Iv

GO Terms for Multiple Endocrine Neoplasia, Type Iv

Biological processes related to Multiple Endocrine Neoplasia, Type Iv according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 negative regulation of cell proliferation GO:0008285 9.61 CDKN1B CDKN2C MEN1
2 phosphorylation GO:0016310 9.56 CDK2 CDKN1B CDKN2C PRKAR1A
3 negative regulation of epithelial cell proliferation GO:0050680 9.4 CDKN1B MEN1
4 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0006977 9.37 CDK2 CDKN1B
5 regulation of cyclin-dependent protein serine/threonine kinase activity GO:0000079 9.32 CDKN1B CDKN2C
6 negative regulation of phosphorylation GO:0042326 9.16 CDKN1B CDKN2C
7 G1/S transition of mitotic cell cycle GO:0000082 9.13 CDK2 CDKN1B CDKN2C
8 negative regulation of cyclin-dependent protein serine/threonine kinase activity GO:0045736 8.8 CDKN1B CDKN2C MEN1

Molecular functions related to Multiple Endocrine Neoplasia, Type Iv according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cyclin-dependent protein serine/threonine kinase activity GO:0004693 9.26 CDK2 CDKN1B
2 kinase activity GO:0016301 9.26 CDK2 CDKN1B CDKN2C PRKAR1A
3 cyclin binding GO:0030332 9.16 CDK2 CDKN1B
4 cyclin-dependent protein serine/threonine kinase inhibitor activity GO:0004861 8.62 CDKN1B CDKN2C

Sources for Multiple Endocrine Neoplasia, Type Iv

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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