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GCCD4
MCID: GLC105
MIFTS: 35

Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency (GCCD4)

Categories: Endocrine diseases, Genetic diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Drugs
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Aliases & Classifications for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

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

Name: Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency 56 73 29 6
Gccd4 56 73
Glucocorticoid Deficiency 4, with or Without Mineralocorticoid Deficiency 56
Familial Glucocorticoid Deficiency 4 73
Glucocorticoid Deficiency 4 71
Fgd4 73

Characteristics:

OMIM:

56
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:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Endocrine diseases
See all MalaCards categories (disease lists)


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

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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). The drugs Paclitaxel and Albumin-Bound Paclitaxel have been mentioned in the context of this disorder. Affiliated tissues include cortex, adrenal cortex and breast, and related phenotypes are cryptorchidism and hyponatremia

OMIM : 56 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)

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

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

(show all 40)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease, type 4h 12.3
2 charcot-marie-tooth disease 11.8
3 tooth disease 11.7
4 peripheral nervous system disease 11.5
5 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.3
6 charcot-marie-tooth disease, axonal, type 2e 11.3
7 charcot-marie-tooth disease and deafness 11.2
8 neuropathy, hereditary sensory and autonomic, type iia 11.2
9 sensory peripheral neuropathy 11.2
10 charcot-marie-tooth disease/hereditary motor and sensory neuropathy 11.2
11 charcot-marie-tooth disease, demyelinating, type 1a 11.1
12 hypertrophic neuropathy of dejerine-sottas 11.1
13 neuropathy, hereditary, with liability to pressure palsies 11.1
14 aarskog-scott syndrome 11.1
15 charcot-marie-tooth disease, demyelinating, type 1c 11.1
16 charcot-marie-tooth disease, type 4b1 11.1
17 charcot-marie-tooth disease, type 4d 11.1
18 charcot-marie-tooth disease, type 4c 11.1
19 charcot-marie-tooth disease, type 4b2 11.1
20 charcot-marie-tooth disease, type 4j 11.1
21 charcot-marie-tooth disease, demyelinating, type 4f 11.1
22 neuromuscular disease 11.1
23 scoliosis 10.3
24 neuropathy 10.3
25 alcohol dependence 10.1
26 amyotrophic lateral sclerosis 1 10.1
27 prostate cancer 10.1
28 kearns-sayre syndrome 10.1
29 prostatic hyperplasia, benign 10.1
30 nasopharyngeal carcinoma 10.1
31 pachyonychia congenita 3 10.1
32 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
33 prostatic hypertrophy 10.1
34 clubfoot 10.1
35 impotence 10.1
36 lateral sclerosis 10.1
37 prostatic adenoma 10.1
38 atrophic muscular disease 10.1
39 foot drop 10.1
40 hereditary neuropathies 10.1

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

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

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 31 occasional (7.5%) HP:0000028
2 hyponatremia 31 occasional (7.5%) HP:0002902
3 precocious puberty 31 occasional (7.5%) HP:0000826
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:

56
Growth Other:
failure to thrive

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

Genitourinary External Genitalia Male:
precocious puberty

Skin Nails Hair Skin:
hyperpigmentation

Metabolic Features:
hypoglycemia
salt wasting
addisonian crisis

Laboratory Abnormalities:
hyponatremia
hyperkalemia
elevated acth
low cortisol level
unresponsive to acth stimulation
more
Endocrine Features:
precocious puberty
hypothyroidism, congenital (rare)

Neurologic Central Nervous System:
seizures, hypoglycemic
coma, hypoglycemic

Clinical features from OMIM:

614736
Sources

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

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Drugs for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paclitaxel Approved, Vet_approved Phase 3 33069-62-4 36314
2 Albumin-Bound Paclitaxel Phase 3
3 Tubulin Modulators Phase 3
4 Halichondrin B Phase 3
5 Antimitotic Agents Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomized Phase III Trial of Eribulin Compared to Standard Weekly Paclitaxel as First- or Second-Line Therapy for Locally Recurrent or Metastatic Breast Cancer Suspended NCT02037529 Phase 3 Eribulin Mesylate;Paclitaxel

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

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

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

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

40
Cortex, Adrenal Cortex, Breast, Prostate, Brain, Retina, Testes
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Publications for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

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

(show all 46)
# Title Authors PMID Year
1
NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects. 6 56
27129361 2016
2
A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency. 6 56
23474776 2013
3
Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. 6 56
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. 56
26070314 2015
5
Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency. 56
25879317 2015
6
A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation. 61
32245826 2020
7
Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease. 61
31852984 2020
8
Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis. 61
31872054 2019
9
FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms. 61
31688594 2019
10
A very mild phenotype of Charcot-Marie-Tooth disease type 4H caused by two novel mutations in FGD4. 61
31152969 2019
11
Tswana traditional health practitioners' perspectives on the management of diabetes and hypertension: a qualitative study using focus group discussions. 61
31934236 2019
12
Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer. 61
30558664 2018
13
Predictive biomarkers of chemotherapy-induced peripheral neuropathy: a review. 61
30044129 2018
14
Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. 61
28902413 2017
15
A novel mutation in FGD4 causes Charcot-Marie-Tooth disease type 4H with cranial nerve involvement. 61
28847448 2017
16
A novel mutation in the FGD4 gene causing Charcot-Marie-Tooth disease. 61
28543957 2017
17
Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model. 61
28321468 2017
18
Mechanisms of Impaired Neutrophil Migration by MicroRNAs in Myelodysplastic Syndromes. 61
28130497 2017
19
The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer. 61
27650539 2016
20
Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients. 61
27736846 2016
21
Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise. 61
27832807 2016
22
Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance). 61
26763541 2016
23
[Peroneal myoatrophy type 4H FGD4 new gene mutation in one case and literature review]. 61
26957070 2016
24
Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families. 61
26400421 2015
25
Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects. 61
26086592 2015
26
Aluminum Nanoparticles Induce ERK and p38MAPK Activation in Rat Brain. 61
24386518 2013
27
The first Japanese case of Charcot-Marie-Tooth disease type 4H with a novel FGD4 c.837-1G>A mutation. 61
23770104 2013
28
Charcot-Marie-Tooth Neuropathy Type 4H – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
23926620 2013
29
A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family. 61
23550889 2013
30
Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes. 61
23781959 2013
31
Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan. 61
23466821 2013
32
p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells. 61
23380069 2013
33
Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells. 61
23171661 2012
34
A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. 61
22843789 2012
35
Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H). 61
22734899 2012
36
Peripheral blood DNA methylation profiles are indicative of head and neck squamous cell carcinoma: an epigenome-wide association study. 61
22430805 2012
37
Genome-wide association study of copy number variants suggests LTBP1 and FGD4 are important for alcohol drinking. 61
22295116 2012
38
Epstein-Barr virus-encoded LMP1 interacts with FGD4 to activate Cdc42 and thereby promote migration of nasopharyngeal carcinoma cells. 61
22589722 2012
39
Genetic spectrum of hereditary neuropathies with onset in the first year of life. 61
21840889 2011
40
Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H. 61
19332693 2009
41
A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H. 61
19221294 2009
42
[Ultrastructural lesions of axonal mitochondria in patients with childhood-onset Charcot-Marie-Tooth disease due to MFN2 mutations]. 61
19718987 2009
43
Histopathological findings in hereditary motor and sensory neuropathy of axonal type with onset in early childhood associated with mitofusin 2 mutations. 61
18957892 2008
44
Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H. 61
17564959 2007
45
Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4. 61
17564972 2007
46
Charcot-Marie-Tooth Neuropathy Type 4 – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
20301641 1998
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Variations for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

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

6 (show all 11) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# 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.600-1deldeletion 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.3027T>G (p.Asn1009Lys)SNV Pathogenic 35542 rs370273690 5:43702754-43702754 5:43702652-43702652
6 NNT NM_182977.3(NNT):c.3022G>C (p.Ala1008Pro)SNV Pathogenic 35543 rs387907234 5:43702749-43702749 5:43702647-43702647
7 NNT NM_182977.3(NNT):c.1259dup (p.His421fs)duplication Pathogenic 218365 rs864309519 5:43644870-43644871 5:43644768-43644769
8 NNT NM_182977.3(NNT):c.644T>C (p.Phe215Ser)SNV Pathogenic 265839 rs886039786 5:43619178-43619178 5:43619076-43619076
9 NNT NM_182977.3(NNT):c.385C>T (p.Arg129Ter)SNV Pathogenic 265843 rs886039789 5:43615953-43615953 5:43615851-43615851
10 NNT NM_182977.3(NNT):c.211C>T (p.Arg71Ter)SNV Pathogenic 265844 rs886039790 5:43613069-43613069 5:43612967-43612967
11 NNT NM_182977.3(NNT):c.98dup (p.Leu33fs)duplication Likely pathogenic 800942 5:43609389-43609390 5:43609287-43609288

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

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

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

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

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

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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