MEN2B
MCID: MLT159
MIFTS: 60

Multiple Endocrine Neoplasia, Type Iib (MEN2B)

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

Aliases & Classifications for Multiple Endocrine Neoplasia, Type Iib

MalaCards integrated aliases for Multiple Endocrine Neoplasia, Type Iib:

Name: Multiple Endocrine Neoplasia, Type Iib 57
Multiple Endocrine Neoplasia Type 2b 12 20 58 44 15 70
Wagenmann-Froboese Syndrome 57 12 20 58
Men2b 57 12 58 72
Multiple Endocrine Neoplasia Iib 57 29 13
Multiple Endocrine Neoplasia, Type 2b 29 6
Mucosal Neuroma Syndrome 12 20
Multiple Endocrine Neoplasia, Type Iii, Formerly; Men3, Formerly 57
Multiple Endocrine Neoplasia, Type Iii, Formerly 57
Neuromata, Mucosal, with Endocrine Tumors 57
Neoplasia, Endocrine, Multiple, Type Iib 39
Multiple Endocrine Neoplasia, Type 3 12
Multiple Endocrine Neoplasia Type 3 58
Multiple Neoplasia 2b 72
Men3, Formerly 57
Men Type Iib 12
Men Iib 57
Men 2b 20

Characteristics:

Orphanet epidemiological data:

58
multiple endocrine neoplasia type 2b
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
medullary thyroid cancer is aggressive and can occur in childhood
fifty percent of cases are sporadic


HPO:

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


Classifications:

Orphanet: 58  
Rare gastroenterological diseases
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:10016
OMIM® 57 162300
OMIM Phenotypic Series 57 PS131100
ICD9CM 34 258.03
MeSH 44 D018814
NCIt 50 C3227
SNOMED-CT 67 61530001
ICD10 32 E31.23
MESH via Orphanet 45 D018814
ICD10 via Orphanet 33 D44.8
UMLS via Orphanet 71 C0025269
Orphanet 58 ORPHA247709
MedGen 41 C0025269
UMLS 70 C0025269

Summaries for Multiple Endocrine Neoplasia, Type Iib

GARD : 20 Multiple endocrine neoplasia type 2B (MEN2B) is a genetic disease in which one or more of the endocrine glands are overactive and form a tumor (neoplasia). Common tumors that may be associated with MEN2B include medullary thyroid carcinoma (MTC) and tumors of the adrenal glands called pheochromocytomas. Other features of MEN2B can include having bumps on the lips, eyelids, and tongue. People with MEN2B typically have a body type with long arms, legs, and fingers. They may also have joints that are very loose (hyperextensible). MEN2B is caused by a specific genetic change ( mutation or pathogenic variant) in the RET gene. The disease is inherited in an autosomal dominant manner. A diagnosis of MEN2B is suspected when a person has a personal or family history of medullary thyroid cancer, pheochromocytoma, or physical findings suggestive of MEN2B. The diagnosis can be confirmed with genetic testing. Treatment for MEN2B typically includes removal of the thyroid and screening for the development of additional tumors. There is another type of multiple endocrine neoplasia type 2 that causes an increased risk for medullary thyroid carcinoma and pheochromocytomas. This disease is known as multiple endocrine neoplasia type 2A (MEN2A).

MalaCards based summary : Multiple Endocrine Neoplasia, Type Iib, also known as multiple endocrine neoplasia type 2b, is related to thyroid carcinoma and neuroma, and has symptoms including constipation and diarrhea. An important gene associated with Multiple Endocrine Neoplasia, Type Iib is RET (Ret Proto-Oncogene), and among its related pathways/superpathways are Signaling by GPCR and Developmental Biology. The drugs Sorafenib and Protein Kinase Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include thyroid, tongue and colon, and related phenotypes are scoliosis and constipation

Disease Ontology : 12 A multiple endocrine neoplasia characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas and intestinal ganglioneuromas, and often a marfanoid habitus and other skeletal abnormalities.

OMIM® : 57 Multiple endocrine neoplasia type IIB (MEN2B) is an autosomal dominant hamartoneoplastic syndrome characterized by aggressive medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuromas, and thickened corneal nerves. Most affected individuals have characteristic physical features, including full lips, thickened eyelids, high-arched palate, and marfanoid habitus. Other more variable features include skeletal anomalies and gastrointestinal problems (review by Morrison and Nevin, 1996). For a discussion of genetic heterogeneity of multiple endocrine neoplasia (MEN), see MEN1 (131100). (162300) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Multiple neoplasia 2B: Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases.

Wikipedia : 73 Multiple endocrine neoplasia type 2B is a genetic disease that causes multiple tumors on the mouth,... more...

Related Diseases for Multiple Endocrine Neoplasia, Type Iib

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

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

(show top 50) (show all 177)
# Related Disease Score Top Affiliating Genes
1 thyroid carcinoma 31.2 RET NTRK1 NCOA4 CALCA
2 neuroma 30.9 RET NF1 GDNF CALCA
3 intestinal obstruction 30.8 RET NRTN GDNF
4 multiple endocrine neoplasia 30.6 SDHD SDHB RET NF1 MEN1 GDNF
5 thyroid carcinoma, familial medullary 30.5 RET PSPN NTRK1 MEN1 GFRA1 GDNF
6 hyperparathyroidism 30.4 RET MEN1 CALCA
7 thyroid gland medullary carcinoma 30.3 RET PSPN NTRK1 NCOA4 MEN1 GFRA1
8 multiple mucosal neuroma 30.2 RET NTRK1 MEN1 GDNF CALCA
9 primary hyperparathyroidism 30.2 RET MEN1 CALCA
10 constipation 30.2 RET NRTN GRP GDNF CALCA
11 parathyroid adenoma 30.1 RET MEN1 CALCA
12 neuroendocrine carcinoma 30.1 MEN1 GRP CALCA
13 thyroid gland follicular carcinoma 29.9 RET PTCH1 NTRK1 NCOA4 CALCA
14 neuroendocrine tumor 29.8 SDHD SDHB RET MEN1 GRP CALCA
15 multiple endocrine neoplasia, type iv 29.7 RET MEN1
16 neurofibromatosis 29.6 SDHD SDHB RET NF1
17 neurofibromatosis, type i 29.6 TMEM127 SDHD SDHB RET NF1 MEN1
18 renal hypodysplasia/aplasia 1 29.6 RET PSPN NRTN GFRA1 GDNF
19 megacolon 29.5 RET PSPN NTRK1 NRTN GFRA1 GDNF
20 multiple endocrine neoplasia, type i 29.5 SDHD SDHB RET NF1 MEN1
21 cowden syndrome 29.4 SDHD SDHB RET NF1 MEN1
22 von hippel-lindau syndrome 28.9 TMEM127 SDHD SDHB SDHAF2 RET NF1
23 paraganglioma 28.9 TMEM127 SDHD SDHB SDHAF2 RET NF1
24 hereditary paraganglioma-pheochromocytoma syndromes 28.8 TMEM127 SDHD SDHB SDHAF2 RET NF1
25 neuroblastoma 28.8 SDHB RET PTCH1 NTRK1 NF1 MEN1
26 hirschsprung disease 1 28.7 RET PTCH1 PSPN NTRK1 NRTN GFRA1
27 pheochromocytoma 28.6 TMEM127 SHC1 SDHD SDHB SDHAF2 RET
28 multiple endocrine neoplasia, type iia 28.0 TMEM127 SHC1 SDHD SDHB SDHAF2 RET
29 adrenal gland pheochromocytoma 10.6
30 struma ovarii 10.4 RET NCOA4
31 atypical follicular adenoma 10.4 RET CALCA
32 nonencapsulated sclerosing carcinoma 10.4 RET CALCA
33 medullary sponge kidney 10.4 RET GDNF
34 ptosis 10.4
35 corneal neovascularization 10.4
36 gangliocytoma 10.4
37 ganglioneuroma 10.4
38 blepharitis 10.4
39 dysphagia 10.4
40 thyroid tumor 10.4
41 hypoganglionosis 10.4 RET GDNF
42 malignant struma ovarii 10.3 RET NCOA4
43 endocrine pancreas disease 10.3 MEN1 CALCA
44 perianal hematoma 10.3 NF1 CALCA
45 neurogenic arthropathy 10.3 NTRK1 CALCA
46 pancreatic somatostatinoma 10.3 NF1 CALCA
47 pancreatic cholera 10.3 MEN1 CALCA
48 hyperparathyroidism 2 with jaw tumors 10.3 RET MEN1
49 brachial plexus lesion 10.3 NF1 GDNF
50 tall cell variant papillary carcinoma 10.3 RET NTRK1

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



Diseases related to Multiple Endocrine Neoplasia, Type Iib

Symptoms & Phenotypes for Multiple Endocrine Neoplasia, Type Iib

Human phenotypes related to Multiple Endocrine Neoplasia, Type Iib:

31 (show all 29)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 HP:0002650
2 constipation 31 HP:0002019
3 kyphosis 31 HP:0002808
4 high palate 31 HP:0000218
5 hyperlordosis 31 HP:0003307
6 global developmental delay 31 HP:0001263
7 thick eyebrow 31 HP:0000574
8 myopathy 31 HP:0003198
9 thick lower lip vermilion 31 HP:0000179
10 failure to thrive in infancy 31 HP:0001531
11 high, narrow palate 31 HP:0002705
12 pectus excavatum 31 HP:0000767
13 joint laxity 31 HP:0001388
14 disproportionate tall stature 31 HP:0001519
15 aganglionic megacolon 31 HP:0002251
16 colonic diverticula 31 HP:0002253
17 pes cavus 31 HP:0001761
18 pheochromocytoma 31 HP:0002666
19 diarrhea 31 HP:0002014
20 generalized hypotonia 31 HP:0001290
21 ganglioneuroma 31 HP:0003005
22 medullary thyroid carcinoma 31 HP:0002865
23 elevated calcitonin 31 HP:0003528
24 nodular goiter 31 HP:0005994
25 parathyroid hyperplasia 31 HP:0008208
26 elevated urinary epinephrine 31 HP:0003639
27 flushing 31 HP:0031284
28 proximal femoral epiphysiolysis 31 HP:0006461
29 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Spine:
scoliosis
kyphosis
lordosis

Muscle Soft Tissue:
myopathy

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Skeletal Feet:
pes cavus

Laboratory Abnormalities:
elevated calcitonin
pentagastrin stimulation test
increased urinary epinephrine

Endocrine Features:
parathyroid hyperplasia

Head And Neck Mouth:
thick lips
high arched palate
neuromas of lips and tongue

Head And Neck Face:
coarse-appearing facies

Skin Nails Hair Skin:
flushing attacks

Abdomen Gastrointestinal:
constipation
diarrhea
ganglioneuroma
megacolon
colonic diverticulosis

Growth Other:
failure to thrive in infancy

Skeletal Limbs:
joint laxity
slipped capital femoral epiphyses

Neoplasia:
pheochromocytoma
ganglioneuroma
medullary thyroid carcinoma
parathyroid disease rare

Head And Neck Neck:
nodular goiter

Neurologic Central Nervous System:
hypotonia
developmental delay

Growth Height:
marfanoid body habitus

Head And Neck Eyes:
pedunculated nodules on eyelid margins
eyelid and corneal neuromas
medullated corneal nerve fibers
thickened, anteverted eyelid
large, prominent eyebrow

Clinical features from OMIM®:

162300 (Updated 05-Apr-2021)

UMLS symptoms related to Multiple Endocrine Neoplasia, Type Iib:


constipation; diarrhea

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

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 9.89 SHC1
2 Decreased viability GR00055-A-2 9.89 SHC1
3 Decreased viability GR00106-A-0 9.89 MEN1 ZNF22
4 Decreased viability GR00221-A-1 9.89 NF1 RET SDHD
5 Decreased viability GR00221-A-2 9.89 NF1 RET SDHD
6 Decreased viability GR00221-A-3 9.89 NTRK1
7 Decreased viability GR00221-A-4 9.89 NF1 RET SDHD
8 Decreased viability GR00240-S-1 9.89 SDHB
9 Decreased viability GR00249-S 9.89 GFRA1 NCOA4 NF1 NTRK1 PTCH1 SDHD
10 Decreased viability GR00301-A 9.89 NTRK1 RET
11 Decreased viability GR00381-A-1 9.89 CALCA GRP SDHD
12 Decreased viability GR00381-A-3 9.89 GRP
13 Decreased viability GR00386-A-1 9.89 GRP NCOA4 NF1 PTCH1 TMEM127
14 Decreased viability GR00402-S-2 9.89 ARTN GRP RET TMEM127

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

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.27 GDNF GFRA1 GRP NF1 NRTN NTRK1
2 cellular MP:0005384 10.17 GDNF GFRA1 MEN1 NCOA4 NF1 PTCH1
3 immune system MP:0005387 10.06 GDNF GFRA1 MEN1 NF1 NRTN NTRK1
4 endocrine/exocrine gland MP:0005379 10.02 GDNF MEN1 NF1 NRTN PTCH1 RET
5 muscle MP:0005369 9.96 GDNF GFRA1 MEN1 NF1 NRTN NTRK1
6 digestive/alimentary MP:0005381 9.95 GDNF GFRA1 MEN1 NF1 NRTN PTCH1
7 nervous system MP:0003631 9.8 ARTN GDNF GFRA1 GRP MEN1 NF1
8 neoplasm MP:0002006 9.7 MEN1 NF1 PTCH1 RET SDHB SDHD
9 normal MP:0002873 9.23 GFRA1 NF1 NTRK1 PTCH1 RET SDHB

Drugs & Therapeutics for Multiple Endocrine Neoplasia, Type Iib

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sorafenib Approved, Investigational Phase 2 284461-73-0 216239 406563
2 Protein Kinase Inhibitors Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase I/II Trial of Vandetanib (ZD6474, ZACTIMA) in Children and Adolescents With Hereditary Medullary Thyroid Carcinoma Completed NCT00514046 Phase 1, Phase 2 Vandetanib
2 Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma Active, not recruiting NCT00390325 Phase 2 Sorafenib Tosylate
3 A Phase 1 Study of Veliparib (ABT-888) in Combination With Capecitabine and Temozolomide in Advanced Well-Differentiated Neuroendocrine Tumors Withdrawn NCT02831179 Phase 1 Capecitabine;Temozolomide;Veliparib
4 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
5 Longitudinal Assessment and Natural History Study of Children and Adults With MEN2A or MEN2B With or Without Medullary Thyroid Carcinoma Recruiting NCT01660984

Search NIH Clinical Center for Multiple Endocrine Neoplasia, Type Iib

Cochrane evidence based reviews: multiple endocrine neoplasia type 2b

Genetic Tests for Multiple Endocrine Neoplasia, Type Iib

Genetic tests related to Multiple Endocrine Neoplasia, Type Iib:

# Genetic test Affiliating Genes
1 Multiple Endocrine Neoplasia, Type 2b 29 RET
2 Multiple Endocrine Neoplasia Iib 29

Anatomical Context for Multiple Endocrine Neoplasia, Type Iib

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

40
Thyroid, Tongue, Colon, Bone, Small Intestine, Liver, Pituitary

Publications for Multiple Endocrine Neoplasia, Type Iib

Articles related to Multiple Endocrine Neoplasia, Type Iib:

(show top 50) (show all 345)
# Title Authors PMID Year
1
Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome). 57 61 6
8880581 1996
2
Parent-of-origin effects in multiple endocrine neoplasia type 2B. 61 57 6
7977365 1994
3
Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. 57 61 6
7906417 1994
4
A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. 57 6 61
7906866 1994
5
Full activation of MEN2B mutant RET by an additional MEN2A mutation or by ligand GDNF stimulation. 6 57
9620546 1998
6
Novel tandem germline RET proto-oncogene mutations in a patient with multiple endocrine neoplasia type 2B: report of a case and a literature review of tandem RET mutations with in silico analysis. 6 61
23468374 2013
7
Multiple endocrine neoplasia type 2B with a RET proto-oncogene A883F mutation displays a more indolent form of medullary thyroid carcinoma compared with a RET M918T mutation. 6 61
21186952 2011
8
RET is constitutively activated by novel tandem mutations that alter the active site resulting in multiple endocrine neoplasia type 2B. 6 61
17047083 2006
9
Phenotypic multiple endocrine neoplasia type 2B, without endocrinopathy or RET gene mutation: implications for management. 57 61
16839263 2006
10
External ophthalmic findings in multiple endocrine neoplasia type 2B. 6 61
15281979 2004
11
Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course. 57 61
11815959 2002
12
A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations. 61 6
10679286 2000
13
Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma. 6 61
10445857 1999
14
Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation. 6 61
10076558 1999
15
Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation. 6 61
9360560 1997
16
Relationship of familial prominent corneal nerves and lesions of the tongue resembling neuromas to multiple endocrine neoplasia type 2B. 57 61
7573303 1995
17
Familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2B map to the same region of chromosome 10 as multiple endocrine neoplasia type 2A. 57 61
1672289 1991
18
Multiple endocrine neoplasia type 2b with a good prognosis. 61 57
2884942 1987
19
Abnormal cutaneous innervation in multiple endocrine neoplasia, type 2b. 61 57
7224387 1981
20
The parathyroid glands in multiple endocrine neoplasia type 2b. 57 61
7377288 1980
21
Multiple endocrine neoplasia, type 2b: phenotype recognition; neurological features and their pathological basis. 57 61
554522 1979
22
Alimentary tract manifestations of multiple endocrine neoplasia, type 2b. 61 57
895196 1977
23
Alimentary-tract ganglioneuromatosis. A major component of the syndrome of multiple endocrine neoplasia, type 2b. 57 61
980061 1976
24
Mucosal ganglioneuromatosis, medullary thyroid carcinoma, and pheochromocytoma: multiple endocrine neoplasia, type 2b. 57 61
1063979 1976
25
Risk Profile of the RET A883F Germline Mutation: An International Collaborative Study. 6
28323957 2017
26
Tandem Germline RET Mutations in a Family Pathogenetic for Multiple Endocrine Neoplasia 2B, Confirmed by a Natural Experiment. 6
25759805 2014
27
Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy. 6
22992277 2012
28
Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome. 57
22258529 2012
29
Ocular signs of multiple endocrine neoplasia type 2B (MEN2B). 20 61
22238409 2012
30
Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10. 6
20979234 2011
31
Familial pediatric endocrine tumors. 6
21934104 2011
32
The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. 6
20664475 2010
33
RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest. 6
19826964 2009
34
Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B. 6
19240193 2009
35
Mutational spectrum of multiple endocrine neoplasia type 2 and sporadic medullary thyroid carcinoma in taiwan. 6
19443294 2009
36
Histopathologic and clinical features of medullary microcarcinoma and C-cell hyperplasia in prophylactic thyroidectomies for medullary carcinoma: a study of 42 cases. 6
18976013 2008
37
Medullary thyroid carcinoma in a 2-month-old male with multiple endocrine neoplasia 2B and symptoms of pseudo-Hirschsprung disease: a case report. 6
17848262 2007
38
Double germline mutations in the RET Proto-oncogene in MEN 2A and MEN 2B kindreds. 6
16705552 2006
39
RET-familial medullary thyroid carcinoma mutants Y791F and S891A activate a Src/JAK/STAT3 pathway, independent of glial cell line-derived neurotrophic factor. 6
15753368 2005
40
Screening of six risk exons of the RET proto-oncogene in families with medullary thyroid carcinoma in the Czech Republic. 6
15531714 2004
41
Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations. 6
12016484 2002
42
A novel germline point mutation, c.2304 G-->T, in codon 768 of the RET proto-oncogene in a patient with medullary thyroid carcinoma. 6
12116277 2002
43
Atypical MEN type 2B associated with two germline RET mutations on the same allele not involving codon 918. 6
11788682 2002
44
Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic patients. 6
11230481 2001
45
The Glu632-Leu633 deletion in cysteine rich domain of Ret induces constitutive dimerization and alters the processing of the receptor protein. 6
10490816 1999
46
Neuromas and prominent corneal nerves without MEN 2B. 57
10189992 1998
47
Four cases of mucosal neuroma syndrome: multiple endocrine neoplasm 2B or not 2B? 57
9435410 1998
48
Germline mutation of RET codon 883 in two cases of de novo MEN 2B. 6
9294615 1997
49
Oncogenic activation of RET by two distinct FMTC mutations affecting the tyrosine kinase domain. 6
9242375 1997
50
The different RET-activating capability of mutations of cysteine 620 or cysteine 634 correlates with the multiple endocrine neoplasia type 2 disease phenotype. 6
9012462 1997

Variations for Multiple Endocrine Neoplasia, Type Iib

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

6 (show top 50) (show all 122)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RET NM_020975.6(RET):c.2631del (p.Arg878fs) Deletion Pathogenic 932072 GRCh37: 10:43615551-43615551
GRCh38: 10:43120103-43120103
2 RET NM_020975.6(RET):c.1852T>G (p.Cys618Gly) SNV Pathogenic 13905 rs76262710 GRCh37: 10:43609096-43609096
GRCh38: 10:43113648-43113648
3 RET NM_020975.6(RET):c.1852T>C (p.Cys618Arg) SNV Pathogenic 13929 rs76262710 GRCh37: 10:43609096-43609096
GRCh38: 10:43113648-43113648
4 RET NM_020975.6(RET):c.2410G>A (p.Val804Met) SNV Pathogenic 13945 rs79658334 GRCh37: 10:43614996-43614996
GRCh38: 10:43119548-43119548
5 RET NM_020975.6(RET):c.2410G>A (p.Val804Met) SNV Pathogenic 37102 rs79658334 GRCh37: 10:43614996-43614996
GRCh38: 10:43119548-43119548
6 RET NM_020975.6(RET):c.2410G>A (p.Val804Met) SNV Pathogenic 549811 rs79658334 GRCh37: 10:43614996-43614996
GRCh38: 10:43119548-43119548
7 RET NM_020975.6(RET):c.2410G>A (p.Val804Met) SNV Pathogenic 549816 rs79658334 GRCh37: 10:43614996-43614996
GRCh38: 10:43119548-43119548
8 RET NM_020975.6(RET):c.2410G>A (p.Val804Met) SNV Pathogenic 549817 rs79658334 GRCh37: 10:43614996-43614996
GRCh38: 10:43119548-43119548
9 RET NM_020975.6(RET):c.1859G>T (p.Cys620Phe) SNV Pathogenic 13928 rs77503355 GRCh37: 10:43609103-43609103
GRCh38: 10:43113655-43113655
10 RET NM_020975.6(RET):c.2753T>C (p.Met918Thr) SNV Pathogenic 549821 rs74799832 GRCh37: 10:43617416-43617416
GRCh38: 10:43121968-43121968
11 RET NM_020975.6(RET):c.2753T>C (p.Met918Thr) SNV Pathogenic 549822 rs74799832 GRCh37: 10:43617416-43617416
GRCh38: 10:43121968-43121968
12 RET NM_020975.6(RET):c.1901G>C (p.Cys634Ser) SNV Pathogenic 13910 rs75996173 GRCh37: 10:43609949-43609949
GRCh38: 10:43114501-43114501
13 RET NM_020975.6(RET):c.2753T>C (p.Met918Thr) SNV Pathogenic/Likely pathogenic 13919 rs74799832 GRCh37: 10:43617416-43617416
GRCh38: 10:43121968-43121968
14 RET NM_020975.6(RET):c.2647_2648delinsTT (p.Ala883Phe) Indel Pathogenic/Likely pathogenic 38629 rs377767429 GRCh37: 10:43615568-43615569
GRCh38: 10:43120120-43120121
15 RET NM_020975.6(RET):c.1893_1898del (p.Asp631_Leu633delinsGlu) Deletion Likely pathogenic 986727 GRCh37: 10:43609941-43609946
GRCh38: 10:43114493-43114498
16 RET NM_020975.6(RET):c.1859G>A (p.Cys620Tyr) SNV Likely pathogenic 13916 rs77503355 GRCh37: 10:43609103-43609103
GRCh38: 10:43113655-43113655
17 RET NM_020975.6(RET):c.3222dup (p.Val1075fs) Duplication Likely pathogenic 979070 GRCh37: 10:43623593-43623594
GRCh38: 10:43128145-43128146
18 RET NM_020975.6(RET):c.2671T>G (p.Ser891Ala) SNV Likely pathogenic 13951 rs75234356 GRCh37: 10:43615592-43615592
GRCh38: 10:43120144-43120144
19 RET NM_020975.6(RET):c.1947G>A (p.Ser649=) SNV Likely pathogenic 24929 rs377767412 GRCh37: 10:43609995-43609995
GRCh38: 10:43114547-43114547
20 RET NM_020975.6(RET):c.2304G>C (p.Glu768Asp) SNV Likely pathogenic 13931 rs78014899 GRCh37: 10:43613840-43613840
GRCh38: 10:43118392-43118392
21 RET NM_020975.6(RET):c.2304G>T (p.Glu768Asp) SNV Likely pathogenic 38611 rs78014899 GRCh37: 10:43613840-43613840
GRCh38: 10:43118392-43118392
22 RET NM_020975.6(RET):c.1902C>G (p.Cys634Trp) SNV Likely pathogenic 13918 rs77709286 GRCh37: 10:43609950-43609950
GRCh38: 10:43114502-43114502
23 RET NM_020975.6(RET):c.1901G>A (p.Cys634Tyr) SNV Likely pathogenic 13909 rs75996173 GRCh37: 10:43609949-43609949
GRCh38: 10:43114501-43114501
24 RET NM_020975.6(RET):c.2410G>C (p.Val804Leu) SNV Likely pathogenic 38613 rs79658334 GRCh37: 10:43614996-43614996
GRCh38: 10:43119548-43119548
25 RET NM_020975.6(RET):c.1888T>C (p.Cys630Arg) SNV Likely pathogenic 24908 rs377767404 GRCh37: 10:43609936-43609936
GRCh38: 10:43114488-43114488
26 RET NM_020975.6(RET):c.1853G>A (p.Cys618Tyr) SNV Likely pathogenic 24901 rs79781594 GRCh37: 10:43609097-43609097
GRCh38: 10:43113649-43113649
27 RET NM_020975.6(RET):c.1900T>C (p.Cys634Arg) SNV Likely pathogenic 13917 rs75076352 GRCh37: 10:43609948-43609948
GRCh38: 10:43114500-43114500
28 RET NM_020975.6(RET):c.1826G>A (p.Cys609Tyr) SNV Likely pathogenic 13933 rs77939446 GRCh37: 10:43609070-43609070
GRCh38: 10:43113622-43113622
29 RET NM_020975.6(RET):c.2372A>T (p.Tyr791Phe) SNV Conflicting interpretations of pathogenicity 13936 rs77724903 GRCh37: 10:43613908-43613908
GRCh38: 10:43118460-43118460
30 RET NM_020975.6(RET):c.874G>A (p.Val292Met) SNV Uncertain significance 24880 rs34682185 GRCh37: 10:43601830-43601830
GRCh38: 10:43106382-43106382
31 RET NM_020975.6(RET):c.2556C>G (p.Ile852Met) SNV Uncertain significance 24955 rs377767426 GRCh37: 10:43615142-43615142
GRCh38: 10:43119694-43119694
32 RET NM_020975.6(RET):c.2611G>A (p.Val871Ile) SNV Uncertain significance 41842 rs145170911 GRCh37: 10:43615532-43615532
GRCh38: 10:43120084-43120084
33 RET NM_020975.6(RET):c.509C>T (p.Thr170Ile) SNV Uncertain significance 41844 rs200547906 GRCh37: 10:43597961-43597961
GRCh38: 10:43102513-43102513
34 RET NM_020975.6(RET):c.667G>A (p.Val223Met) SNV Uncertain significance 136122 rs587780815 GRCh37: 10:43600441-43600441
GRCh38: 10:43104993-43104993
35 RET NM_020975.6(RET):c.1150C>G (p.Pro384Ala) SNV Uncertain significance 216713 rs536298339 GRCh37: 10:43604565-43604565
GRCh38: 10:43109117-43109117
36 RET NM_020975.6(RET):c.2611G>A (p.Val871Ile) SNV Uncertain significance 41842 rs145170911 GRCh37: 10:43615532-43615532
GRCh38: 10:43120084-43120084
37 RET NM_020975.6(RET):c.1897C>G (p.Leu633Val) SNV Uncertain significance 216718 rs267607010 GRCh37: 10:43609945-43609945
GRCh38: 10:43114497-43114497
38 RET NM_020975.6(RET):c.2522C>T (p.Pro841Leu) SNV Uncertain significance 24947 rs149891333 GRCh37: 10:43615108-43615108
GRCh38: 10:43119660-43119660
39 RET NM_020975.6(RET):c.3314C>T (p.Ala1105Val) SNV Uncertain significance 201136 rs532862288 GRCh37: 10:43623686-43623686
GRCh38: 10:43128238-43128238
40 RET NM_020975.6(RET):c.1702G>A (p.Gly568Ser) SNV Uncertain significance 132762 rs140464432 GRCh37: 10:43608354-43608354
GRCh38: 10:43112906-43112906
41 RET NM_020975.6(RET):c.2225C>T (p.Thr742Met) SNV Uncertain significance 187701 rs773256580 GRCh37: 10:43612120-43612120
GRCh38: 10:43116672-43116672
42 RET NM_020975.6(RET):c.1934_1936del (p.Ser645del) Deletion Uncertain significance 543756 rs1416677590 GRCh37: 10:43609980-43609982
GRCh38: 10:43114532-43114534
43 RET NM_020975.6(RET):c.2225C>T (p.Thr742Met) SNV Uncertain significance 187701 rs773256580 GRCh37: 10:43612120-43612120
GRCh38: 10:43116672-43116672
44 RET NM_020975.6(RET):c.2531G>T (p.Arg844Leu) SNV Uncertain significance 24952 rs55947360 GRCh37: 10:43615117-43615117
GRCh38: 10:43119669-43119669
45 RET NM_020975.6(RET):c.972G>C (p.Trp324Cys) SNV Uncertain significance 188078 rs758298916 GRCh37: 10:43601928-43601928
GRCh38: 10:43106480-43106480
46 RET NM_020975.6(RET):c.335G>A (p.Arg112His) SNV Uncertain significance 136120 rs587780814 GRCh37: 10:43596168-43596168
GRCh38: 10:43100720-43100720
47 RET NM_020975.6(RET):c.2449C>T (p.Arg817Cys) SNV Uncertain significance 136111 rs142318626 GRCh37: 10:43615035-43615035
GRCh38: 10:43119587-43119587
48 RET NM_020975.6(RET):c.3185A>G (p.Tyr1062Cys) SNV Uncertain significance 135181 rs587778659 GRCh37: 10:43622168-43622168
GRCh38: 10:43126720-43126720
49 RET NM_020975.6(RET):c.2611G>A (p.Val871Ile) SNV Uncertain significance 41842 rs145170911 GRCh37: 10:43615532-43615532
GRCh38: 10:43120084-43120084
50 RET NM_020975.6(RET):c.3149G>A (p.Arg1050Gln) SNV Uncertain significance 241358 rs200956659 GRCh37: 10:43622132-43622132
GRCh38: 10:43126684-43126684

UniProtKB/Swiss-Prot genetic disease variations for Multiple Endocrine Neoplasia, Type Iib:

72
# Symbol AA change Variation ID SNP ID
1 RET p.Met918Thr VAR_006342 rs74799832
2 RET p.Thr946Met VAR_006345
3 RET p.Ala883Phe VAR_009485 rs377767429

Cosmic variations for Multiple Endocrine Neoplasia, Type Iib:

9 (show top 50) (show all 113)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM88301868 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.389T>G p.V130G 3:10146562-10146562 0
2 COSM90654925 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.260T>C p.V87A 3:10142107-10142107 0
3 COSM88294143 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.260T>C p.V87A 3:10142107-10142107 0
4 COSM90652830 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.373G>T p.V125F 3:10149819-10149819 0
5 COSM90658470 VHL adrenal gland,NS,pheochromocytoma,benign c.244C>G p.R82G 3:10142091-10142091 0
6 COSM88293303 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.475A>G p.K159E 3:10149798-10149798 0
7 COSM88288959 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.482G>A p.R161Q 3:10149805-10149805 0
8 COSM88296074 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.250G>C p.V84L 3:10142097-10142097 0
9 COSM88291454 VHL adrenal gland,NS,pheochromocytoma,benign c.245G>T p.R82L 3:10142092-10142092 0
10 COSM88292246 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.227T>A p.F76Y 3:10142074-10142074 0
11 COSM88297427 VHL adrenal gland,NS,pheochromocytoma,benign c.244C>G p.R82G 3:10142091-10142091 0
12 COSM90652721 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.368A>G p.Q123R 3:10149814-10149814 0
13 COSM88292324 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.496G>T p.V166F 3:10149819-10149819 0
14 COSM90657160 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.250G>C p.V84L 3:10142097-10142097 0
15 COSM88305342 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.492G>T p.Q164H 3:10149815-10149815 0
16 COSM90653943 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.352A>G p.K118E 3:10149798-10149798 0
17 COSM90668341 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.369G>T p.Q123H 3:10149815-10149815 0
18 COSM88292236 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.491A>G p.Q164R 3:10149814-10149814 0
19 COSM88289571 VHL adrenal gland,NS,pheochromocytoma,benign c.341-1G>T p.? 3:10146513-10146513 0
20 COSM90651871 VHL adrenal gland,NS,pheochromocytoma,benign c.245G>T p.R82L 3:10142092-10142092 0
21 COSM88294223 VHL adrenal gland,NS,pheochromocytoma,benign c.499C>T p.R167W 3:10149822-10149822 0
22 COSM90649980 VHL adrenal gland,NS,pheochromocytoma,benign c.341-3274G>T p.? 3:10146513-10146513 0
23 COSM90655004 VHL adrenal gland,NS,pheochromocytoma,benign c.376C>T p.R126W 3:10149822-10149822 0
24 COSM90652730 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.227T>A p.F76Y 3:10142074-10142074 0
25 COSM90648957 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.359G>A p.R120Q 3:10149805-10149805 0
26 COSM90664073 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.341-3225T>G p.? 3:10146562-10146562 0
27 COSM90811579 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.2753T>C p.M918T 10:43121968-43121968 0
28 COSM92347003 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.2753T>C p.M918T 10:43121968-43121968 0
29 COSM142343426 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.1289+3268T>C p.? 10:43114500-43114500 0
30 COSM142343204 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.*102T>C p.? 10:43121968-43121968 0
31 COSM92347226 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.1900T>C p.C634R 10:43114500-43114500 0
32 COSM90811811 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.1900T>C p.C634R 10:43114500-43114500 0
33 COSM93530486 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.226G>T p.E76* 17:31159031-31159031 0
34 COSM93656552 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1885G>A p.G629R 17:31225134-31225134 0
35 COSM93692982 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.5665G>T p.E1889* 17:31330351-31330351 0
36 COSM93650970 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1466A>G p.Y489C 17:31214524-31214524 0
37 COSM120509060 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1466A>G p.Y489C 17:31214524-31214524 0
38 COSM93535461 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.3158C>A p.S1053* 17:31230886-31230886 0
39 COSM109968573 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.226G>T p.E76* 17:31159031-31159031 0
40 COSM109960979 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1466A>G p.Y489C 17:31214524-31214524 0
41 COSM93512112 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1885G>A p.G629R 17:31225134-31225134 0
42 COSM93508888 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.205-1G>C p.? 17:31159009-31159009 0
43 COSM93650443 NF1 adrenal gland,NS,pheochromocytoma,benign c.1307C>A p.S436* 17:31206286-31206286 0
44 COSM93509879 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.2409+1G>A p.? 17:31227607-31227607 0
45 COSM120509488 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.205-1G>C p.? 17:31159009-31159009 0
46 COSM93507010 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.7237C>T p.Q2413* 17:31349230-31349230 0
47 COSM93662933 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.7582C>T p.Q2528* 17:31352381-31352381 0
48 COSM93654948 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.7646C>G p.S2549* 17:31356490-31356490 0
49 COSM93504734 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1721+3A>T p.? 17:31221932-31221932 0
50 COSM93507162 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1466A>G p.Y489C 17:31214524-31214524 0

Expression for Multiple Endocrine Neoplasia, Type Iib

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

Pathways for Multiple Endocrine Neoplasia, Type Iib

Pathways related to Multiple Endocrine Neoplasia, Type Iib according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.88 SHC1 RET PTCH1 PSPN NTRK1 NRTN
2
Show member pathways
13.22 SHC1 RET PSPN NRTN NF1 GFRA1
3
Show member pathways
13.03 SHC1 RET PSPN NRTN NF1 GFRA1
4 12.27 RET NTRK1 NF1 CALCA
5
Show member pathways
11.4 SHC1 RET PSPN NRTN GFRA1 GDNF
6 11.04 SHC1 RET GFRA1 GDNF
7 10.92 PSPN NRTN GFRA1 GDNF ARTN
8 10.03 SHC1 RET GFRA1 GDNF

GO Terms for Multiple Endocrine Neoplasia, Type Iib

Cellular components related to Multiple Endocrine Neoplasia, Type Iib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon GO:0030424 9.35 RET NTRK1 NRTN NF1 CALCA
2 mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) GO:0005749 8.62 SDHD SDHB

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

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of cell proliferation GO:0008285 9.91 TMEM127 PTCH1 NTRK1 NF1 MEN1
2 nervous system development GO:0007399 9.8 RET PSPN NTRK1 NRTN GFRA1 GDNF
3 positive regulation of MAPK cascade GO:0043410 9.77 SHC1 RET NTRK1
4 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.67 SHC1 RET NTRK1 NRTN
5 neural crest cell migration GO:0001755 9.63 RET NRTN GDNF
6 tricarboxylic acid cycle GO:0006099 9.61 SDHD SDHB SDHAF2
7 innervation GO:0060384 9.58 RET NTRK1
8 response to pain GO:0048265 9.58 RET CALCA
9 detection of temperature stimulus involved in sensory perception of pain GO:0050965 9.57 NTRK1 CALCA
10 enteric nervous system development GO:0048484 9.56 RET GDNF
11 axon guidance GO:0007411 9.56 SHC1 RET PSPN NTRK1 NRTN GFRA1
12 commissural neuron axon guidance GO:0071679 9.55 PTCH1 GDNF
13 smooth muscle tissue development GO:0048745 9.54 PTCH1 NF1
14 glial cell-derived neurotrophic factor receptor signaling pathway GO:0035860 9.52 RET GFRA1
15 lymphocyte migration into lymphoid organs GO:0097021 9.49 RET ARTN
16 mitochondrial electron transport, succinate to ubiquinone GO:0006121 9.48 SDHD SDHAF2
17 peripheral nervous system development GO:0007422 9.43 NF1 GDNF ARTN
18 Peyer's patch morphogenesis GO:0061146 9.4 RET ARTN
19 sympathetic nervous system development GO:0048485 9.33 NTRK1 NF1 GDNF
20 MAPK cascade GO:0000165 9.28 SHC1 RET PSPN NRTN NF1 MEN1

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

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 9.7 PSPN NRTN GRP GFRA1 GDNF CALCA
2 growth factor activity GO:0008083 9.56 PSPN NRTN GDNF ARTN
3 receptor tyrosine kinase binding GO:0030971 9.35 SHC1 PSPN NRTN GDNF ARTN
4 ubiquinone binding GO:0048039 9.32 SDHD SDHB
5 glial cell-derived neurotrophic factor receptor binding GO:0030116 8.92 PSPN NRTN GDNF ARTN

Sources for Multiple Endocrine Neoplasia, Type Iib

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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