GCCD4
MCID: GLC105
MIFTS: 33

Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency (GCCD4)

Categories: Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

MalaCards integrated aliases for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

Name: Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency 57 73 29 6
Gccd4 57 73
Glucocorticoid Deficiency 4, with or Without Mineralocorticoid Deficiency 57
Familial Glucocorticoid Deficiency 4 73
Glucocorticoid Deficiency 4 71
Fgd4 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable features may be present
patients may present with recurrent illnesses or infections, or shock
disease is life-threatening if untreated


HPO:

31
glucocorticoid deficiency 4 with or without mineralocorticoid deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

UniProtKB/Swiss-Prot : 73 Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency: A form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.

MalaCards based summary : Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency, also known as gccd4, is related to charcot-marie-tooth disease, type 4h and charcot-marie-tooth disease. An important gene associated with Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency is NNT (Nicotinamide Nucleotide Transhydrogenase). Affiliated tissues include cortex, adrenal cortex and breast, and related phenotypes are precocious puberty and cryptorchidism

OMIM® : 57 Familial glucocorticoid deficiency is a rare autosomal recessive disorder characterized by an inability of the adrenal cortex to produce cortisol in response to stimulation by adrenocorticotropic hormone (ACTH). Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, hypoglycemia, convulsions, and shock. The disease is life-threatening if untreated (summary by Meimaridou et al., 2012). For a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200). (614736) (Updated 05-Mar-2021)

Related Diseases for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Diseases related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 42)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease, type 4h 11.4
2 charcot-marie-tooth disease 11.2
3 tooth disease 11.2
4 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.1
5 charcot-marie-tooth disease, axonal, type 2e 11.1
6 neuropathy 11.0
7 charcot-marie-tooth disease and deafness 11.0
8 neuropathy, hereditary sensory and autonomic, type iia 11.0
9 aarskog-scott syndrome 11.0
10 sensory peripheral neuropathy 11.0
11 peripheral nervous system disease 10.9
12 charcot-marie-tooth disease, demyelinating, type 1b 10.8
13 charcot-marie-tooth disease, demyelinating, type 1a 10.8
14 hypertrophic neuropathy of dejerine-sottas 10.8
15 neuropathy, hereditary, with liability to pressure palsies 10.8
16 charcot-marie-tooth disease, demyelinating, type 1c 10.8
17 charcot-marie-tooth disease, type 4b1 10.8
18 charcot-marie-tooth disease, type 4d 10.8
19 charcot-marie-tooth disease, type 4c 10.8
20 charcot-marie-tooth disease, type 4b2 10.8
21 charcot-marie-tooth disease, type 4j 10.8
22 charcot-marie-tooth disease, demyelinating, type 4f 10.8
23 neuromuscular disease 10.8
24 scoliosis 10.1
25 hereditary neuropathies 10.0
26 alcohol dependence 9.8
27 amyotrophic lateral sclerosis 1 9.8
28 prostate cancer 9.8
29 kearns-sayre syndrome 9.8
30 prostatic hyperplasia, benign 9.8
31 nasopharyngeal carcinoma 9.8
32 pachyonychia congenita 3 9.8
33 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.8
34 generalized epilepsy with febrile seizures plus 9.8
35 prostatic hypertrophy 9.8
36 clubfoot 9.8
37 impotence 9.8
38 lateral sclerosis 9.8
39 prostatic adenoma 9.8
40 muscular atrophy 9.8
41 atrophic muscular disease 9.8
42 foot drop 9.8

Graphical network of the top 20 diseases related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:



Diseases related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency

Symptoms & Phenotypes for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Human phenotypes related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 precocious puberty 31 occasional (7.5%) HP:0000826
2 cryptorchidism 31 occasional (7.5%) HP:0000028
3 hyponatremia 31 occasional (7.5%) HP:0002902
4 hyperkalemia 31 occasional (7.5%) HP:0002153
5 congenital hypothyroidism 31 occasional (7.5%) HP:0000851
6 renal salt wasting 31 occasional (7.5%) HP:0000127
7 hypoglycemic coma 31 occasional (7.5%) HP:0001325
8 failure to thrive 31 HP:0001508
9 hypoglycemia 31 HP:0001943
10 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Growth Other:
failure to thrive

Endocrine Features:
precocious puberty
hypothyroidism, congenital (rare)

Genitourinary Internal Genitalia Male:
cryptorchidism
testicular enlargement
testicular adrenal rest tumors
leydig cell tumors

Skin Nails Hair Skin:
hyperpigmentation

Genitourinary External Genitalia Male:
precocious puberty

Metabolic Features:
hypoglycemia
salt wasting
addisonian crisis

Laboratory Abnormalities:
hyponatremia
hyperkalemia
elevated acth
low cortisol level
unresponsive to acth stimulation
more
Neurologic Central Nervous System:
seizures, hypoglycemic
coma, hypoglycemic

Clinical features from OMIM®:

614736 (Updated 05-Mar-2021)

Drugs & Therapeutics for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Search Clinical Trials , NIH Clinical Center for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency

Genetic Tests for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Genetic tests related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

# Genetic test Affiliating Genes
1 Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency 29 NNT

Anatomical Context for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

MalaCards organs/tissues related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

40
Cortex, Adrenal Cortex, Breast, Prostate, Brain, Retina, Neutrophil

Publications for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Articles related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

(show all 50)
# Title Authors PMID Year
1
NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects. 6 57
27129361 2016
2
A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency. 57 6
23474776 2013
3
Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. 57 6
22634753 2012
4
Combined mineralocorticoid and glucocorticoid deficiency is caused by a novel founder nicotinamide nucleotide transhydrogenase mutation that alters mitochondrial morphology and increases oxidative stress. 57
26070314 2015
5
Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency. 57
25879317 2015
6
Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). 61
33399082 2020
7
MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4. 61
32772928 2020
8
Genetic variation in Charcot-Marie-Tooth genes contributes to sensitivity to paclitaxel-induced peripheral neuropathy. 61
32700628 2020
9
Global Gene Expression Characterization of Circulating Tumor Cells in Metastasic Castration-Resistant Prostate Cancer Patients. 61
32630240 2020
10
A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation. 61
32245826 2020
11
Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease. 61
31852984 2020
12
Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis. 61
31872054 2019
13
FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms. 61
31688594 2019
14
A very mild phenotype of Charcot-Marie-Tooth disease type 4H caused by two novel mutations in FGD4. 61
31152969 2019
15
Tswana traditional health practitioners' perspectives on the management of diabetes and hypertension: a qualitative study using focus group discussions. 61
31934236 2019
16
Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer. 61
30558664 2018
17
Predictive biomarkers of chemotherapy-induced peripheral neuropathy: a review. 61
30044129 2018
18
Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. 61
28902413 2017
19
A novel mutation in FGD4 causes Charcot-Marie-Tooth disease type 4H with cranial nerve involvement. 61
28847448 2017
20
A novel mutation in the FGD4 gene causing Charcot-Marie-Tooth disease. 61
28543957 2017
21
Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model. 61
28321468 2017
22
Mechanisms of Impaired Neutrophil Migration by MicroRNAs in Myelodysplastic Syndromes. 61
28130497 2017
23
The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer. 61
27650539 2016
24
Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients. 61
27736846 2016
25
Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise. 61
27832807 2016
26
Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance). 61
26763541 2016
27
[Peroneal myoatrophy type 4H FGD4 new gene mutation in one case and literature review]. 61
26957070 2016
28
Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families. 61
26400421 2015
29
Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects. 61
26086592 2015
30
Aluminum Nanoparticles Induce ERK and p38MAPK Activation in Rat Brain. 61
24386518 2013
31
Charcot-Marie-Tooth Neuropathy Type 4H – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
23926620 2013
32
The first Japanese case of Charcot-Marie-Tooth disease type 4H with a novel FGD4 c.837-1G>A mutation. 61
23770104 2013
33
A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family. 61
23550889 2013
34
Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes. 61
23781959 2013
35
Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan. 61
23466821 2013
36
p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells. 61
23380069 2013
37
Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells. 61
23171661 2012
38
A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. 61
22843789 2012
39
Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H). 61
22734899 2012
40
Peripheral blood DNA methylation profiles are indicative of head and neck squamous cell carcinoma: an epigenome-wide association study. 61
22430805 2012
41
Epstein-Barr virus-encoded LMP1 interacts with FGD4 to activate Cdc42 and thereby promote migration of nasopharyngeal carcinoma cells. 61
22589722 2012
42
Genome-wide association study of copy number variants suggests LTBP1 and FGD4 are important for alcohol drinking. 61
22295116 2012
43
Genetic spectrum of hereditary neuropathies with onset in the first year of life. 61
21840889 2011
44
Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H. 61
19332693 2009
45
A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H. 61
19221294 2009
46
[Ultrastructural lesions of axonal mitochondria in patients with childhood-onset Charcot-Marie-Tooth disease due to MFN2 mutations]. 61
19718987 2009
47
Histopathological findings in hereditary motor and sensory neuropathy of axonal type with onset in early childhood associated with mitofusin 2 mutations. 61
18957892 2008
48
Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H. 61
17564959 2007
49
Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4. 61
17564972 2007
50
Charcot-Marie-Tooth Neuropathy Type 4 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
20301641 1998

Variations for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

ClinVar genetic disease variations for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

6 (show all 15)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NNT NM_182977.3(NNT):c.1598C>T (p.Ala533Val) SNV Pathogenic 35538 rs387907232 5:43649402-43649402 5:43649300-43649300
2 NNT NM_182977.3(NNT):c.600-1del Deletion Pathogenic 35539 rs786205344 5:43619133-43619133 5:43619031-43619031
3 NNT NM_182977.3(NNT):c.2930T>C (p.Leu977Pro) SNV Pathogenic 35540 rs387907233 5:43700274-43700274 5:43700172-43700172
4 NNT NM_182977.3(NNT):c.1107_1110del (p.Thr369_His370insTer) Deletion Pathogenic 35541 rs786205345 5:43644719-43644722 5:43644617-43644620
5 NNT NM_182977.3(NNT):c.3022G>C (p.Ala1008Pro) SNV Pathogenic 35543 rs387907234 5:43702749-43702749 5:43702647-43702647
6 NNT NM_182977.3(NNT):c.644T>C (p.Phe215Ser) SNV Pathogenic 265839 rs886039786 5:43619178-43619178 5:43619076-43619076
7 NNT NM_182977.3(NNT):c.385C>T (p.Arg129Ter) SNV Pathogenic 265843 rs886039789 5:43615953-43615953 5:43615851-43615851
8 NNT NM_182977.3(NNT):c.211C>T (p.Arg71Ter) SNV Pathogenic 265844 rs886039790 5:43613069-43613069 5:43612967-43612967
9 NNT NM_182977.3(NNT):c.1259dup (p.His421fs) Duplication Pathogenic 218365 rs864309519 5:43644870-43644871 5:43644768-43644769
10 NNT NM_182977.3(NNT):c.3027T>G (p.Asn1009Lys) SNV Pathogenic 35542 rs370273690 5:43702754-43702754 5:43702652-43702652
11 NNT NM_182977.3(NNT):c.98dup (p.Leu33fs) Duplication Likely pathogenic 800942 rs1579966821 5:43609389-43609390 5:43609287-43609288
12 NNT NM_182977.3(NNT):c.598G>A (p.Gly200Ser) SNV Likely pathogenic 265842 rs886039788 5:43616166-43616166 5:43616064-43616064
13 NNT NM_182977.3(NNT):c.1575dup (p.Pro526fs) Duplication Likely pathogenic 930557 5:43649378-43649379 5:43649276-43649277
14 NNT NM_182977.3(NNT):c.80G>A (p.Arg27His) SNV Benign 703892 rs34241095 5:43609377-43609377 5:43609275-43609275
15 NNT NM_182977.3(NNT):c.1098+17T>C SNV Benign 931319 5:43644444-43644444 5:43644342-43644342

UniProtKB/Swiss-Prot genetic disease variations for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

73 (show all 11)
# Symbol AA change Variation ID SNP ID
1 NNT p.Ser193Asn VAR_068781 rs867004061
2 NNT p.Thr357Ala VAR_068782 rs144740886
3 NNT p.His365Pro VAR_068783
4 NNT p.Pro437Leu VAR_068784 rs781183677
5 NNT p.Ala533Val VAR_068785 rs387907232
6 NNT p.Gly664Arg VAR_068786 rs371979800
7 NNT p.Gly678Arg VAR_068787
8 NNT p.Gly862Asp VAR_068788 rs147442141
9 NNT p.Leu977Pro VAR_068789 rs387907233
10 NNT p.Ala1008Pro VAR_068790 rs387907234
11 NNT p.Asn1009Lys VAR_068791 rs370273690

Expression for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Search GEO for disease gene expression data for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency.

Pathways for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

GO Terms for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Sources for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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