GCCD4
MCID: GLC105
MIFTS: 33

Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency (GCCD4)

Categories: Endocrine diseases, Genetic diseases, Rare diseases
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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 5
Gccd4 57 73
Glucocorticoid Deficiency 4, with or Without Mineralocorticoid Deficiency 57
Familial Glucocorticoid Deficiency 4 73
Glucocorticoid Deficiency 4 71
Fgd4 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable features may be present
patients may present with recurrent illnesses or infections, or shock
disease is life-threatening if untreated


Classifications:



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

UniProtKB/Swiss-Prot: 73 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 adrenal cortex, cortex and prostate, 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 08-Dec-2022)

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 top 50) (show all 63)
# 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 11.1
5 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.1
6 charcot-marie-tooth disease, axonal, type 2e 11.1
7 charcot-marie-tooth disease and deafness 11.0
8 aarskog-scott syndrome 11.0
9 peripheral nervous system disease 10.9
10 charcot-marie-tooth disease, demyelinating, type 1b 10.9
11 charcot-marie-tooth disease, demyelinating, type 1a 10.8
12 hypertrophic neuropathy of dejerine-sottas 10.8
13 neuropathy, hereditary, with liability to pressure palsies 10.8
14 charcot-marie-tooth disease, type 4a 10.8
15 charcot-marie-tooth disease, demyelinating, type 1c 10.8
16 charcot-marie-tooth disease, type 4b1 10.8
17 charcot-marie-tooth disease, type 4d 10.8
18 charcot-marie-tooth disease, type 4c 10.8
19 charcot-marie-tooth disease, type 4b2 10.8
20 neuropathy, hereditary motor and sensory, russe type 10.8
21 charcot-marie-tooth disease, dominant intermediate b 10.8
22 charcot-marie-tooth disease, demyelinating, type 1f 10.8
23 charcot-marie-tooth disease, type 4j 10.8
24 charcot-marie-tooth disease, dominant intermediate e 10.8
25 charcot-marie-tooth disease, demyelinating, type 4f 10.8
26 charcot-marie-tooth disease, type 4b3 10.8
27 charcot-marie-tooth disease, recessive intermediate c 10.8
28 charcot-marie-tooth disease, axonal, type 2t 10.8
29 charcot-marie-tooth disease intermediate type 10.8
30 polyneuropathy due to drug 10.8
31 sensory peripheral neuropathy 10.8
32 neuromuscular disease 10.8
33 roussy-levy hereditary areflexic dystasia 10.4
34 hereditary sensory neuropathy 10.4
35 scoliosis 10.2
36 hereditary neuropathies 10.0
37 alcohol dependence 9.8
38 amyotrophic lateral sclerosis 1 9.8
39 esophageal cancer 9.8
40 polycystic ovary syndrome 1 9.8
41 glucocorticoid deficiency 1 9.8
42 kearns-sayre syndrome 9.8
43 prostatic hyperplasia, benign 9.8
44 nasopharyngeal carcinoma 9.8
45 ewing sarcoma 9.8
46 pachyonychia congenita 3 9.8
47 tatton-brown-rahman syndrome 9.8
48 generalized epilepsy with febrile seizures plus 9.8
49 cauda equina syndrome 9.8
50 polycystic ovary syndrome 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:

30 (show all 10)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 precocious puberty 30 Occasional (7.5%) HP:0000826
2 cryptorchidism 30 Occasional (7.5%) HP:0000028
3 hyponatremia 30 Occasional (7.5%) HP:0002902
4 hyperkalemia 30 Occasional (7.5%) HP:0002153
5 congenital hypothyroidism 30 Occasional (7.5%) HP:0000851
6 renal salt wasting 30 Occasional (7.5%) HP:0000127
7 hypoglycemic coma 30 Occasional (7.5%) HP:0001325
8 seizure 30 HP:0001250
9 failure to thrive 30 HP:0001508
10 hypoglycemia 30 HP:0001943

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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 08-Dec-2022)

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...

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

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

MalaCards : Adrenal Cortex, Cortex, Prostate, Breast, Retina, Neutrophil, Brain

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

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

(show top 50) (show all 61)
# Title Authors PMID Year
1
NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects. 57 5
27129361 2016
2
A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency. 57 5
23474776 2013
3
Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. 57 5
22634753 2012
4
Parental exome analysis identifies shared carrier status for a second recessive disorder in couples with an affected child. 5
33223529 2021
5
Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency. 57
25879317 2015
6
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
7
Imbalance of NRG1-ERBB2/3 signalling underlies altered myelination in Charcot-Marie-Tooth disease 4H. 62
36314052 2022
8
Integrated Analysis of Cortex Single-Cell Transcriptome and Serum Proteome Reveals the Novel Biomarkers in Alzheimer's Disease. 62
36009085 2022
9
Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients. 62
35884569 2022
10
Current profile of Charcot-Marie-Tooth disease in Africa: A systematic review. 62
35383421 2022
11
Atorvastatin reduces IOP in ocular hypertension in vivo and suppresses ECM in trabecular meshwork perhaps via FGD4. 62
35417030 2022
12
Pathology of the peripheral neuropathy Charcot-Marie-Tooth disease type 4H in Holstein Friesian cattle with a splice site mutation in FGD4. 62
35300540 2022
13
Sibling Cases of Charcot-Marie-Tooth Disease Type 4H with a Homozygous FGD4 Mutation and Cauda Equina Thickening. 62
34148957 2021
14
Non-additive association analysis using proxy phenotypes identifies novel cattle syndromes. 62
34045765 2021
15
Polymorphism of FGD4 and myelosuppression in patients with esophageal squamous cell carcinoma. 62
33709789 2021
16
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). 62
33399082 2021
17
The Importance of Multiple Gene Analysis for Diagnosis and Differential Diagnosis in Charcot Marie Tooth Disease. 62
34169998 2021
18
Genetic variation in Charcot-Marie-Tooth genes contributes to sensitivity to paclitaxel-induced peripheral neuropathy. 62
32700628 2020
19
MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4. 62
32772928 2020
20
Global Gene Expression Characterization of Circulating Tumor Cells in Metastasic Castration-Resistant Prostate Cancer Patients. 62
32630240 2020
21
A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation. 62
32245826 2020
22
Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease. 62
31852984 2020
23
Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis. 62
31872054 2019
24
FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms. 62
31688594 2019
25
A very mild phenotype of Charcot-Marie-Tooth disease type 4H caused by two novel mutations in FGD4. 62
31152969 2019
26
Tswana traditional health practitioners' perspectives on the management of diabetes and hypertension: a qualitative study using focus group discussions. 62
31934236 2019
27
Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer. 62
30558664 2018
28
Predictive biomarkers of chemotherapy-induced peripheral neuropathy: a review. 62
30044129 2018
29
Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. 62
28902413 2017
30
A novel mutation in FGD4 causes Charcot-Marie-Tooth disease type 4H with cranial nerve involvement. 62
28847448 2017
31
A novel mutation in the FGD4 gene causing Charcot-Marie-Tooth disease. 62
28543957 2017
32
Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model. 62
28321468 2017
33
Mechanisms of Impaired Neutrophil Migration by MicroRNAs in Myelodysplastic Syndromes. 62
28130497 2017
34
Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients. 62
27736846 2016
35
Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise. 62
27832807 2016
36
The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer. 62
27650539 2016
37
Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance). 62
26763541 2016
38
[Peroneal myoatrophy type 4H FGD4 new gene mutation in one case and literature review]. 62
26957070 2016
39
Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families. 62
26400421 2015
40
Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects. 62
26086592 2015
41
Aluminum Nanoparticles Induce ERK and p38MAPK Activation in Rat Brain. 62
24386518 2013
42
Charcot-Marie-Tooth Neuropathy Type 4H – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 62
23926620 2013
43
The first Japanese case of Charcot-Marie-Tooth disease type 4H with a novel FGD4 c.837-1G>A mutation. 62
23770104 2013
44
A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family. 62
23550889 2013
45
Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes. 62
23781959 2013
46
Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan. 62
23466821 2013
47
p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells. 62
23380069 2013
48
Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells. 62
23171661 2012
49
A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. 62
22843789 2012
50
Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H). 62
22734899 2012

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

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

5 (show all 26)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NNT NM_182977.3(NNT):c.1598C>T (p.Ala533Val) SNV Pathogenic
35538 rs387907232 GRCh37: 5:43649402-43649402
GRCh38: 5:43649300-43649300
2 NNT NM_182977.3(NNT):c.600-1del DEL Pathogenic
35539 rs786205344 GRCh37: 5:43619133-43619133
GRCh38: 5:43619031-43619031
3 NNT NM_182977.3(NNT):c.2930T>C (p.Leu977Pro) SNV Pathogenic
35540 rs387907233 GRCh37: 5:43700274-43700274
GRCh38: 5:43700172-43700172
4 NNT NM_182977.3(NNT):c.1107_1110del (p.Thr369_His370insTer) DEL Pathogenic
35541 rs786205345 GRCh37: 5:43644719-43644722
GRCh38: 5:43644617-43644620
5 NNT NM_182977.3(NNT):c.3022G>C (p.Ala1008Pro) SNV Pathogenic
35543 rs387907234 GRCh37: 5:43702749-43702749
GRCh38: 5:43702647-43702647
6 NNT NM_182977.3(NNT):c.1259dup (p.His421fs) DUP Pathogenic
218365 rs864309519 GRCh37: 5:43644870-43644871
GRCh38: 5:43644768-43644769
7 NNT NM_182977.3(NNT):c.644T>C (p.Phe215Ser) SNV Pathogenic
265839 rs886039786 GRCh37: 5:43619178-43619178
GRCh38: 5:43619076-43619076
8 NNT NM_182977.3(NNT):c.385C>T (p.Arg129Ter) SNV Pathogenic
265843 rs886039789 GRCh37: 5:43615953-43615953
GRCh38: 5:43615851-43615851
9 NNT NM_182977.3(NNT):c.211C>T (p.Arg71Ter) SNV Pathogenic
265844 rs886039790 GRCh37: 5:43613069-43613069
GRCh38: 5:43612967-43612967
10 NNT NM_182977.3(NNT):c.2274del (p.Ile758fs) DEL Pathogenic
1119993 GRCh37: 5:43656155-43656155
GRCh38: 5:43656053-43656053
11 NNT NM_182977.3(NNT):c.1089del (p.Leu362_Tyr363insTer) DEL Pathogenic
1705295 GRCh37: 5:43644418-43644418
GRCh38: 5:43644316-43644316
12 NNT NM_182977.3(NNT):c.2635-1G>T SNV Pathogenic
1705519 GRCh37: 5:43675612-43675612
GRCh38: 5:43675510-43675510
13 NNT NM_182977.3(NNT):c.3027T>G (p.Asn1009Lys) SNV Pathogenic
35542 rs370273690 GRCh37: 5:43702754-43702754
GRCh38: 5:43702652-43702652
14 NNT NM_182977.3(NNT):c.98dup (p.Leu33fs) DUP Likely Pathogenic
800942 rs1579966821 GRCh37: 5:43609389-43609390
GRCh38: 5:43609287-43609288
15 NNT NM_182977.3(NNT):c.1575dup (p.Pro526fs) DUP Likely Pathogenic
930557 rs1739624229 GRCh37: 5:43649378-43649379
GRCh38: 5:43649276-43649277
16 NNT NM_182977.3(NNT):c.598G>A (p.Gly200Ser) SNV Likely Pathogenic
265842 rs886039788 GRCh37: 5:43616166-43616166
GRCh38: 5:43616064-43616064
17 NNT NM_182977.3(NNT):c.1424C>T (p.Thr475Met) SNV Uncertain Significance
1030250 rs141791856 GRCh37: 5:43645592-43645592
GRCh38: 5:43645490-43645490
18 NNT NM_182977.3(NNT):c.1817T>C (p.Val606Ala) SNV Uncertain Significance
1030251 rs139379760 GRCh37: 5:43651940-43651940
GRCh38: 5:43651838-43651838
19 NNT NM_182977.3(NNT):c.1880C>T (p.Ser627Leu) SNV Uncertain Significance
1030252 rs41271081 GRCh37: 5:43653136-43653136
GRCh38: 5:43653034-43653034
20 NNT NM_182977.3(NNT):c.2778C>A (p.Ser926Arg) SNV Uncertain Significance
1030253 rs1451092520 GRCh37: 5:43675756-43675756
GRCh38: 5:43675654-43675654
21 NNT NM_182977.3(NNT):c.1822G>A (p.Gly608Arg) SNV Uncertain Significance
1687180 GRCh37: 5:43651945-43651945
GRCh38: 5:43651843-43651843
22 NNT NM_182977.3(NNT):c.-26T>C SNV Benign
1325907 GRCh37: 5:43609272-43609272
GRCh38: 5:43609170-43609170
23 NNT NM_182977.3(NNT):c.152-26_152-25insA INSERT Benign
1325908 GRCh37: 5:43612984-43612985
GRCh38: 5:43612882-43612883
24 NNT NM_182977.3(NNT):c.80G>A (p.Arg27His) SNV Benign
703892 rs34241095 GRCh37: 5:43609377-43609377
GRCh38: 5:43609275-43609275
25 NNT NM_182977.3(NNT):c.1098+17T>C SNV Benign
931319 rs16873430 GRCh37: 5:43644444-43644444
GRCh38: 5:43644342-43644342
26 NNT NM_182977.3(NNT):c.46C>T (p.Leu16=) SNV Benign
1174913 GRCh37: 5:43609343-43609343
GRCh38: 5:43609241-43609241

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 rs1447408865
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 rs1474421419
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...

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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