MCID: MLT086
MIFTS: 52

Multiple Endocrine Neoplasia, Type Iv

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

Aliases & Classifications for Multiple Endocrine Neoplasia, Type Iv

MalaCards integrated aliases for Multiple Endocrine Neoplasia, Type Iv:

Name: Multiple Endocrine Neoplasia, Type Iv 53 12 13 69
Multiple Endocrine Neoplasia Type 4 12 55 14
Men4 53 55 71
Multiple Endocrine Neoplasia, Type 4 28
Multiple Endocrine Neoplasia 4 71

Characteristics:

Orphanet epidemiological data:

55
multiple endocrine neoplasia type 4
Inheritance: Autosomal dominant,Not applicable;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable manifestations
onset of tumors usually in adulthood


HPO:

31
multiple endocrine neoplasia, type iv:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 55  
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 multiple endocrine neoplasia and carney complex variant, and has symptoms including diarrhea, hyperparathyroidism and extrahepatic cholestasis. 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 prostate, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

Description from OMIM: 610755

Related Diseases for Multiple Endocrine Neoplasia, Type Iv

Diseases in the Multiple Endocrine Neoplasia family:

Multiple Endocrine Neoplasia, Type I Multiple Endocrine Neoplasia, Type Iib
Multiple Endocrine Neoplasia, Type Iia Multiple Endocrine Neoplasia, Type Iv
Multiple Endocrine Neoplasia Type 1 and Type 2

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

(show all 35)
# Related Disease Score Top Affiliating Genes
1 multiple endocrine neoplasia 29.9 CDKN1B MEN1 PRKAR1A
2 carney complex variant 29.2 AIP CDKN1B MEN1 PRKAR1A
3 multiple endocrine neoplasia, type i 28.4 CDKN1B CDKN2C MEN1 PRKAR1A PRL
4 silent pituitary adenoma 10.2 AIP MEN1
5 null pituitary adenoma 10.2 AIP MEN1
6 familial isolated pituitary adenoma 10.2 AIP CDKN1B
7 pituitary adenoma 1, multiple types 10.1 AIP PRL
8 pituitary apoplexy 10.1 AIP PRL
9 gigantism 10.1 AIP PRL
10 lentigines 10.1 MEN1 PRKAR1A
11 hyperpituitarism 10.1 AIP PRL
12 lipomatosis 10.1 MEN1 PRKAR1A
13 adrenal cortex disease 10.0 PRKAR1A PRL
14 adrenal gland disease 10.0 PRKAR1A PRL
15 pituitary gland disease 10.0 MEN1 PRL
16 adrenal gland hyperfunction 9.9 PRKAR1A PRL
17 hyperparathyroidism 9.9 CDKN1B MEN1 PRKAR1A
18 hormone producing pituitary cancer 9.9 AIP MEN1 PRKAR1A
19 retinal cancer 9.8 CDK2 CDKN1B
20 functioning pituitary adenoma 9.8 AIP MEN1 PRL
21 endocrine organ benign neoplasm 9.8 AIP MEN1 PRL
22 pituitary tumors 9.8 AIP MEN1 PRL
23 organ system benign neoplasm 9.8 AIP MEN1 PRL
24 parathyroid adenoma 9.8 CDKN2C MEN1
25 cell type benign neoplasm 9.8 AIP MEN1 PRL
26 pituitary adenoma 9.8 AIP MEN1 PRL
27 acromegaly 9.8 AIP MEN1 PRL
28 sensory system cancer 9.8 CDK2 CDKN1B
29 adenoma 9.8 AIP MEN1 PRL
30 growth hormone secreting pituitary adenoma 9.8 AIP PRKAR1A PRL
31 ocular cancer 9.7 CDK2 CDKN1B
32 autosomal genetic disease 9.7 MEN1 PRKAR1A
33 nervous system cancer 9.6 CDK2 CDKN1B
34 primary hyperparathyroidism 9.5 CDKN1B MEN1 PRKAR1A PRL
35 pituitary adenoma, prolactin-secreting 9.5 AIP MEN1 PRKAR1A PRL

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:

53
Endocrine Features:
parathyroid adenoma
pituitary adenoma
acromegaly
carcinoid tumors

Respiratory Airways:
bronchial carcinoid

Genitourinary Kidneys:
renal angiomyolipoma

Neoplasia:
pancreatic endocrine neoplasia
papillary thyroid cancer
neuroendocrine cervical carcinoma


Clinical features from OMIM:

610755

Human phenotypes related to Multiple Endocrine Neoplasia, Type Iv:

55 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 diarrhea 55 31 frequent (33%) Frequent (79-30%) HP:0002014
2 hyperparathyroidism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000843
3 extrahepatic cholestasis 55 31 occasional (7.5%) Occasional (29-5%) HP:0012334
4 increased glucagon level 55 31 occasional (7.5%) Occasional (29-5%) HP:0030688
5 carcinoid tumor 55 31 Occasional (29-5%) HP:0100570
6 parathyroid adenoma 55 31 hallmark (90%) Very frequent (99-80%) HP:0002897
7 hypercalcemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0003072
8 elevated circulating parathyroid hormone level 55 31 hallmark (90%) Very frequent (99-80%) HP:0003165
9 parathyroid hyperplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0008208
10 hyperinsulinemic hypoglycemia 55 31 frequent (33%) Frequent (79-30%) HP:0000825
11 growth hormone excess 55 31 frequent (33%) Frequent (79-30%) HP:0000845
12 thyroid adenoma 55 31 frequent (33%) Frequent (79-30%) HP:0000854
13 subcutaneous lipoma 55 31 frequent (33%) Frequent (79-30%) HP:0001031
14 zollinger-ellison syndrome 55 31 frequent (33%) Frequent (79-30%) HP:0002044
15 episodic abdominal pain 55 31 frequent (33%) Frequent (79-30%) HP:0002574
16 pituitary adenoma 55 31 Frequent (79-30%) HP:0002893
17 peptic ulcer 55 31 frequent (33%) Frequent (79-30%) HP:0004398
18 pituitary prolactin cell adenoma 55 31 frequent (33%) Frequent (79-30%) HP:0006767
19 adrenocortical adenoma 55 31 frequent (33%) Frequent (79-30%) HP:0008256
20 fasting hyperinsulinemia 55 31 frequent (33%) Frequent (79-30%) HP:0008283
21 angiofibromas 55 31 frequent (33%) Frequent (79-30%) HP:0010615
22 pituitary growth hormone cell adenoma 55 31 frequent (33%) Frequent (79-30%) HP:0011760
23 pituitary null cell adenoma 55 31 frequent (33%) Frequent (79-30%) HP:0011761
24 insulinoma 55 31 frequent (33%) Frequent (79-30%) HP:0012197
25 esophagitis 55 31 frequent (33%) Frequent (79-30%) HP:0100633
26 confetti-like hypopigmented macules 55 31 occasional (7.5%) Occasional (29-5%) HP:0007449
27 pituitary corticotropic cell adenoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0008291
28 erythema 55 31 occasional (7.5%) Occasional (29-5%) HP:0010783
29 increased urinary cortisol level 55 31 occasional (7.5%) Occasional (29-5%) HP:0012030
30 thymoma 55 31 very rare (1%) Very rare (<4-1%) HP:0100522
31 cervix cancer 55 31 occasional (7.5%) Occasional (29-5%) HP:0030079
32 testicular neoplasm 55 31 occasional (7.5%) Occasional (29-5%) HP:0010788
33 renal angiomyolipoma 55 31 frequent (33%) Frequent (79-30%) HP:0006772
34 pulmonary carcinoid tumor 55 31 frequent (33%) Frequent (79-30%) HP:0030445
35 parathyroid carcinoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0006780
36 abnormality of the endocrine system 55 Very frequent (99-80%)
37 neuroendocrine neoplasm 55 Frequent (79-30%)
38 abnormality of pancreas physiology 55 Frequent (79-30%)
39 hypercortisolism 55 Occasional (29-5%)
40 increased circulating cortisol level 31 occasional (7.5%) HP:0003118

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

25 (show all 22)
# 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 MEN1 PRKAR1A CDK2
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:

43
# 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 CDKN1B CDKN2C MEN1 PRKAR1A AIP CDK2
3 cellular MP:0005384 9.93 PRKAR1A AIP CDK2 CDKN1B CDKN2C MEN1
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 9.73 AIP CDK2 CDKN1B CDKN2C PRKAR1A 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)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dutasteride Approved, Investigational Phase 1, Phase 2 164656-23-9 6918296 152945
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:


# 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:

# Genetic test Affiliating Genes
1 Multiple Endocrine Neoplasia, Type 4 28 CDKN1B

Anatomical Context for Multiple Endocrine Neoplasia, Type Iv

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

38
Thyroid, Pituitary, Prostate, Cervix, Pancreas

Publications for Multiple Endocrine Neoplasia, Type Iv

Articles related to Multiple Endocrine Neoplasia, Type Iv:

# Title Authors Year
1
Functional characterization of a CDKN1B mutation in a Sardinian kindred with multiple endocrine neoplasia type 4 (MEN4). ( 25416039 )
2014
2
Multiple endocrine neoplasia type 4. ( 23652671 )
2013

Variations for Multiple Endocrine Neoplasia, Type Iv

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

6 (show all 20)
# 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
20 CDKN1B NM_004064.4(CDKN1B): c.267C> G (p.Tyr89Ter) single nucleotide variant Pathogenic rs532903617 GRCh38 Chromosome 12, 12718106: 12718106

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:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of cell proliferation GO:0008285 9.63 CDKN1B CDKN2C MEN1
2 phosphorylation GO:0016310 9.56 CDK2 CDKN1B CDKN2C PRKAR1A
3 negative regulation of epithelial cell proliferation GO:0050680 9.43 CDKN1B MEN1
4 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0006977 9.4 CDK2 CDKN1B
5 negative regulation of cell cycle GO:0045786 9.37 CDKN1B MEN1
6 regulation of cyclin-dependent protein serine/threonine kinase activity GO:0000079 9.32 CDKN1B CDKN2C
7 negative regulation of phosphorylation GO:0042326 9.16 CDKN1B CDKN2C
8 G1/S transition of mitotic cell cycle GO:0000082 9.13 CDK2 CDKN1B CDKN2C
9 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:

# 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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....