MCID: FML063
MIFTS: 58

Familial Glucocorticoid Deficiency

Categories: Endocrine diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Familial Glucocorticoid Deficiency

MalaCards integrated aliases for Familial Glucocorticoid Deficiency:

Name: Familial Glucocorticoid Deficiency 12 20 43 58 36 15
Glucocorticoid Deficiency 43 6 70
Acth Resistance 20 43
Hereditary Unresponsiveness to Adrenocorticotropic Hormone 43
Glucocorticoid Deficiency, Familial 73
Isolated Glucocorticoid Deficiency 43
Adrenal Unresponsiveness to Acth 43
Glucocorticoid Deficiency 1 70

Characteristics:

Orphanet epidemiological data:

58
familial glucocorticoid deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

Classifications:

Orphanet: 58  
Rare endocrine diseases


Summaries for Familial Glucocorticoid Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 361 Definition Familial glucocorticoid deficiency (FGD) is a group of primary adrenal insufficiencies characterized clinically by neonatal hyperpigmentation, hypoglycemia, failure to thrive, and recurrent infections, and biochemically by glucocorticoid deficiency without mineralocorticoid deficiency. Epidemiology The prevalence is unknown. In Ireland there is a prevalence of around 1/200,000, but this is likely to be skewed by a high prevalence in the Irish Traveler sub-population. Clinical description FGD usually presents in infancy or early childhood with hyperpigmentation of the skin and gums (present at birth or that develops over time), hypoglycemic seizures and failure to thrive. Recurrent infections are also a common finding (and may be the presenting sign in older children). Weakness, fatigue, weight loss, anorexia, vomiting, flank or abdominal pain, constipation and diarrhea are additional symptoms seen in some patients due to hypocortisolemia. Hypoglycemic crises resulting in convulsions can lead to coma or death if untreated and recurrent hypolglycemia may lead to neurological sequelae (i.e. learning disabilities, intellectual deficit, and sometimes severe, neuronal damage leading to major sensory and motor defects such as quadriplegia). Tall stature has been reported in some patients with FGD, typically those with MC2R gene defects. MRAP defects have been associated with a more severe disease and an earlier age of onset while a milder phenotype is seen in those with defects in the MCM4 gene (Irish Traveler FGD). Etiology FGD is due, in most cases, to defects in the adrenocorticotropin (ACTH) receptor, or its signaling pathway, resulting in a failure of the cells of zona fasciculata in the adrenal cortex to respond appropriately to adrenocorticotrophic hormone (ACTH), leading to a glucocorticoid deficiency. These defects are most commonly caused by mutations in MC2R (18p11.2), accounting for 25% of cases, and MRAP (21q22.1), accounting for 20% of cases. Other mutations reported in patients with FGD include MCM4 (8q12-q13), probably uniquely in the Irish Traveler population; NNT (5p12), accounting for around 15% of cases; and TXNRD2 (22q11.21). Certain partially inactivating mutations of STAR (8p11.2) or CYP11A1 (15q23-q24) can cause a phenotype that masquerades as FGD. Diagnostic methods Diagnosis is based on clinical and laboratory findings. Patients have high plasma ACTH and low serum morning cortisol levels that do not respond to exogenous ACTH stimulation. Mineralocorticoid function is normal. Molecular genetic testing revealing a mutation in one of the disease causing genes confirms diagnosis of FGD. Differential diagnosis The main differential diagnosis of FGD is Addison's disease (usually of autoimmune origin), in which case a mineralocorticoid deficiency is present. Other differential diagnoses include triple A syndrome, congenital adrenal hyperplasia and other acquired causes of primary adrenal insufficiency (see these terms). Antenatal diagnosis Prenatal diagnosis is possible in families with a known disease causing mutation but is rarely performed. Genetic counseling FDG is inherited in an autosomal recessive manner. Genetic counseling is possible. Management and treatment Treatment consists of a replacement therapy with oral hydrocortisone. A dosage of 10-12 mg/m2/day (usually divided into three doses) normalizes cortisol and reduces, but rarely normalizes, ACTH. Dose modification is necessary during stresses such as surgery or intercurrent illness, and patients should have injectable hydrocortisone available for emergencies and carry a medical alert type bracelet or card. Prompt and adequate treatment of a hypoglycemic crisis is essential. Treatment is life-long. Prognosis The prognosis is good for patients who are diagnosed and treated early. Only when left untreated is FGD a disease with high morbidity (neurological sequelae) and mortality.

MalaCards based summary : Familial Glucocorticoid Deficiency, also known as glucocorticoid deficiency, is related to glucocorticoid deficiency 1 and glucocorticoid deficiency 2. An important gene associated with Familial Glucocorticoid Deficiency is MC2R (Melanocortin 2 Receptor), and among its related pathways/superpathways are Aldosterone synthesis and secretion and Corticotropin-releasing hormone signaling pathway. The drugs Dexamethasone acetate and Dexamethasone have been mentioned in the context of this disorder. Affiliated tissues include adrenal gland, cortex and adrenal cortex, and related phenotypes are decreased circulating cortisol level and failure to thrive

Disease Ontology : 12 An adrenal cortex disease that is characterized by insufficent production of glucocorticoids.

MedlinePlus Genetics : 43 Familial glucocorticoid deficiency is a condition that occurs when the adrenal glands, which are hormone-producing glands located on top of each kidney, do not produce certain hormones called glucocorticoids. These hormones, which include cortisol and corticosterone, aid in immune system function, play a role in maintaining normal blood sugar levels, help trigger nerve cell signaling in the brain, and serve many other purposes in the body.A shortage of adrenal hormones (adrenal insufficiency) causes the signs and symptoms of familial glucocorticoid deficiency. These signs and symptoms often begin in infancy or early childhood. Most affected children first develop low blood sugar (hypoglycemia). These hypoglycemic children can fail to grow and gain weight at the expected rate (failure to thrive). If left untreated, hypoglycemia can lead to seizures, learning difficulties, and other neurological problems. Hypoglycemia that is left untreated for prolonged periods can lead to neurological damage and death. Other features of familial glucocorticoid deficiency can include recurrent infections and skin coloring darker than that of other family members (hyperpigmentation).There are multiple types of familial glucocorticoid deficiency, which are distinguished by their genetic cause.

KEGG : 36 Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by glucocorticoid deficiency despite high levels of plasma ACTH. Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including recurrent illnesses or infections, hypoglycemia, convulsions, failure to thrive and shock. The disease is life threatening if untreated. Glucocorticoid replacement is the recommended treatment. It has been reported that FGD is caused by mutation of the ACTH receptor (MC2R) and the accessory protein (MRAP).

Wikipedia : 73 Glucocorticoid deficiency 1 is an adrenocortical failure characterized by low levels of plasma cortisol... more...

Related Diseases for Familial Glucocorticoid Deficiency

Diseases related to Familial Glucocorticoid Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 122)
# Related Disease Score Top Affiliating Genes
1 glucocorticoid deficiency 1 33.1 POMC MRAP MC2R
2 glucocorticoid deficiency 2 33.0 MRAP-AS1 MRAP GCCD2
3 achalasia-addisonianism-alacrima syndrome 30.5 STAR POMC NR0B1 NNT MRAP MC2R
4 hypoaldosteronism 30.2 REN POMC
5 hypoadrenocorticism, familial 29.9 STAR REN POMC NR0B1 MC2R HSD3B2
6 lipoid congenital adrenal hyperplasia 29.8 STAR REN POMC NR0B1 MRAP MC2R
7 glucocorticoid deficiency 3 11.5
8 glucocorticoid deficiency 4 with or without mineralocorticoid deficiency 11.5
9 glucocorticoid deficiency 5 11.3
10 adrenocortical unresponsiveness to acth with postreceptor defect 11.2
11 adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiency 11.1
12 disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency 11.0
13 autosomal recessive disease 10.6
14 dowling-degos disease 1 10.5
15 hypoglycemia 10.4
16 waterhouse-friderichsen syndrome 10.4 POMC MC2R
17 premenstrual tension 10.4 REN POMC
18 corticosteroid-binding globulin deficiency 10.4 POMC MC2R
19 benign essential hypertension 10.4 REN POMC
20 hyperaldosteronism, familial, type i 10.4 REN POMC MC2R
21 acute adrenal insufficiency 10.3 REN POMC CYP11A1
22 blount's disease 10.3 MRAP2 MC4R
23 inappropriate adh syndrome 10.3 REN POMC
24 adrenal rest tumor 10.3 POMC MC2R HSD3B2
25 pseudohypoaldosteronism, type i, autosomal recessive 10.3 REN MC2R HSD3B2
26 leydig cell tumor 10.3 STAR NR0B1 CYP11A1
27 graves disease 1 10.3 TXNRD2 POMC
28 adrenal cortical adenoma 10.3 REN POMC MC2R CYP11A1
29 adrenal adenoma 10.3 REN POMC MC2R CYP11A1
30 conn's syndrome 10.2 REN POMC MC2R CYP11A1
31 achalasia 10.2
32 adrenal hypoplasia, congenital 10.2 STAR POMC NR0B1 MC2R HSD3B2
33 adrenal cortical carcinoma 10.2 STAR POMC NR0B1 MC2R CYP11A1
34 corticosterone methyloxidase type i deficiency 10.2 STAR REN POMC NR0B1 HSD3B2
35 ovarian disease 10.2 STAR REN POMC CYP11A1
36 anorexia nervosa 10.2 POMC MC4R MC3R
37 hyperandrogenism 10.2 POMC MC4R HSD3B2 CYP11A1
38 46,xy sex reversal 2 10.2 STAR NR0B1 MC2R HSD3B2 CYP11A1
39 adrenal carcinoma 10.2 STAR REN POMC HSD3B2 CYP11A1
40 disorder of sexual development 10.2 STAR POMC NR0B1 HSD3B2 CYP11A1
41 pseudohermaphroditism 10.2 STAR POMC NR0B1 HSD3B2 CYP11A1
42 overnutrition 10.2 REN POMC MC4R
43 adrenal cortical hypofunction 10.2 STAR REN POMC NR0B1 MC2R CYP11A1
44 premature menopause 10.2 STAR POMC NR0B1 CYP11A1
45 cryptorchidism, unilateral or bilateral 10.2 STAR POMC NR0B1 HSD3B2 CYP11A1
46 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 10.2 TXNRD2 NR0B1 NNT MCM4 MC2R CYP11A1
47 tricuspid valve disease 10.2 REN MC3R
48 46,xy sex reversal 10.1 STAR POMC NR0B1 MC2R HSD3B2 CYP11A1
49 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 10.1 STAR POMC NR0B1 NNT HSD3B2 CYP11A1
50 ocular motor apraxia 10.1

Graphical network of the top 20 diseases related to Familial Glucocorticoid Deficiency:



Diseases related to Familial Glucocorticoid Deficiency

Symptoms & Phenotypes for Familial Glucocorticoid Deficiency

Human phenotypes related to Familial Glucocorticoid Deficiency:

58 31 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 decreased circulating cortisol level 58 31 obligate (100%) Obligate (100%) HP:0008163
2 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
3 hypotension 58 31 hallmark (90%) Very frequent (99-80%) HP:0002615
4 generalized hyperpigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007440
5 abnormality of circulating adrenocorticotropin level 58 31 hallmark (90%) Very frequent (99-80%) HP:0011043
6 ketotic hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0012734
7 impaired cortisol response to insulin stimulation test 58 31 hallmark (90%) Very frequent (99-80%) HP:0031076
8 decreased circulating dehydroepiandrosterone level 58 31 hallmark (90%) Very frequent (99-80%) HP:0031214
9 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
10 vomiting 58 31 frequent (33%) Frequent (79-30%) HP:0002013
11 anorexia 58 31 frequent (33%) Frequent (79-30%) HP:0002039
12 chronic fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0012432
13 hyponatremia 58 31 frequent (33%) Frequent (79-30%) HP:0002902
14 weight loss 58 31 frequent (33%) Frequent (79-30%) HP:0001824
15 hyperkalemia 58 31 frequent (33%) Frequent (79-30%) HP:0002153
16 diarrhea 58 31 frequent (33%) Frequent (79-30%) HP:0002014
17 episodic abdominal pain 58 31 frequent (33%) Frequent (79-30%) HP:0002574
18 renal salt wasting 58 31 frequent (33%) Frequent (79-30%) HP:0000127
19 hypernatriuria 58 31 frequent (33%) Frequent (79-30%) HP:0012605
20 hypoglycemic seizures 58 31 frequent (33%) Frequent (79-30%) HP:0002173
21 precocious puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000826
22 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
23 tall stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0000098
24 decreased circulating aldosterone level 58 31 occasional (7.5%) Occasional (29-5%) HP:0004319
25 testicular adrenal rest tumor 58 31 occasional (7.5%) Occasional (29-5%) HP:0025451
26 intellectual disability 58 31 very rare (1%) Very rare (<4-1%) HP:0001249
27 tetraplegia 58 31 very rare (1%) Very rare (<4-1%) HP:0002445
28 hypertrophic cardiomyopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0001639
29 azoospermia 58 31 very rare (1%) Very rare (<4-1%) HP:0000027
30 recurrent urinary tract infections 58 31 very rare (1%) Very rare (<4-1%) HP:0000010
31 congenital hypothyroidism 58 31 very rare (1%) Very rare (<4-1%) HP:0000851
32 hypoglycemic coma 58 31 very rare (1%) Very rare (<4-1%) HP:0001325
33 leydig cell neoplasia 58 31 very rare (1%) Very rare (<4-1%) HP:0100618
34 autoimmunity 58 Excluded (0%)
35 recurrent infections 58 Frequent (79-30%)
36 adrenal insufficiency 58 Obligate (100%)

GenomeRNAi Phenotypes related to Familial Glucocorticoid Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.17 HSD3B2 MC2R MC4R MC5R NR0B1 POMC

MGI Mouse Phenotypes related to Familial Glucocorticoid Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.61 AAAS CYP11A1 MC2R MC5R MCM4 MRAP
2 homeostasis/metabolism MP:0005376 9.44 AAAS CYP11A1 MC2R MC3R MC4R MC5R

Drugs & Therapeutics for Familial Glucocorticoid Deficiency

Drugs for Familial Glucocorticoid Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dexamethasone acetate Approved, Investigational, Vet_approved Phase 2 1177-87-3
2
Dexamethasone Approved, Investigational, Vet_approved Phase 2 50-02-2 5743
3 glucocorticoids Phase 2
4 Gastrointestinal Agents Phase 2
5 Hormone Antagonists Phase 2
6 Hormones Phase 2
7 Antineoplastic Agents, Hormonal Phase 2
8 Anti-Inflammatory Agents Phase 2
9 Antiemetics Phase 2
10
Nicotinamide Approved, Investigational 98-92-0 936
11
Vitamin C Approved, Nutraceutical 50-81-7 5785 54670067
12
Niacin Approved, Investigational, Nutraceutical 59-67-6 938
13 Nutrients
14 Micronutrients
15 Mineralocorticoids
16 Trace Elements
17 Vitamins
18 Protective Agents
19 Antioxidants
20 Nicotinic Acids
21 Vitamin B3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Developmental Clinical Studies - Reversing Endometrial Glucocorticoid Deficiency in Heavy Menstrual Bleeding Completed NCT01769820 Phase 2 Dexamethasone;placebo
2 Ascorbic Acid Treatment for Patients With Combined Mineralocorticoid and Glucocorticoid Deficiency Secondary to Nicotinamide Nucleotide Transhydrogenase Mutation Unknown status NCT02838472 Ascorbic Acid

Search NIH Clinical Center for Familial Glucocorticoid Deficiency

Genetic Tests for Familial Glucocorticoid Deficiency

Anatomical Context for Familial Glucocorticoid Deficiency

MalaCards organs/tissues related to Familial Glucocorticoid Deficiency:

40
Adrenal Gland, Cortex, Adrenal Cortex, Pituitary, Thyroid, Hypothalamus, Thymus

Publications for Familial Glucocorticoid Deficiency

Articles related to Familial Glucocorticoid Deficiency:

(show top 50) (show all 476)
# Title Authors PMID Year
1
Primary Adrenocortical Insufficiency Case Series: Genetic Etiologies More Common than Expected. 6 61
26650942 2016
2
A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency. 61 6
23474776 2013
3
Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. 61 6
22634753 2012
4
Short stature in a patient with familial glucocorticoid deficiency. 6 61
21932602 2011
5
Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2. 6 61
19558534 2010
6
Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency. 61 6
19170705 2009
7
The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface. 6 61
18840636 2008
8
A novel adrenocorticotropin receptor mutation alters its structure and function, causing familial glucocorticoid deficiency. 6 61
18492762 2008
9
Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. 6 61
17223989 2007
10
Unusual presentation of familial glucocorticoid deficiency with a novel MRAP mutation. 6 61
16868047 2006
11
Novel compound heterozygous mutation of the MC2R gene in a patient with familial glucocorticoid deficiency. 6 61
17128565 2006
12
Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. 61 6
15654338 2005
13
Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay. 6 61
12213892 2002
14
Functional characterization of naturally occurring mutations of the human adrenocorticotropin receptor: poor correlation of phenotype and genotype. 6 61
10443676 1999
15
Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency. 61 6
8636348 1996
16
Adrenocorticotropin receptor gene mutations in familial glucocorticoid deficiency: relationships with clinical features in four families. 61 6
7829641 1995
17
Molecular insights into inherited ACTH resistance syndromes. 6 61
18407210 1994
18
Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene. 6 61
8227361 1993
19
Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. 61 6
8094489 1993
20
Parental exome analysis identifies shared carrier status for a second recessive disorder in couples with an affected child. 6
33223529 2021
21
NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects. 6
27129361 2016
22
A Chinese child with hyperpigmentation diagnosed with familial glucocorticoid deficiency type 1 using whole-exome sequencing. 61
33342750 2021
23
Primary Adrenal Insufficiency in Childhood: Data From a Large Nationwide Cohort. 61
33247909 2021
24
Pediatric Primary Adrenal Insufficiency: A 21-year Single Center Experience 61
32938577 2021
25
Clinical and molecular characterization of thirty Chinese patients with congenital lipoid adrenal hyperplasia. 61
33227378 2021
26
Venoarterial extracorporeal membrane oxygenation as bridge to effective treatment in a 19-year-old woman with acute adrenal crisis: a case report. 61
33644667 2021
27
Masked type 1 diabetes mellitus (T1DM) unveiled by glucocorticoid replacement: a case of simultaneous development of T1DM and hypophysitis in an elderly woman. 61
32669510 2020
28
Emerging roles of melanocortin receptor accessory proteins (MRAP and MRAP2) in physiology and pathophysiology. 61
32679290 2020
29
STAR mutations causing non‑classical lipoid adrenal hyperplasia manifested as familial glucocorticoid deficiency. 61
32627004 2020
30
Identification of scavenger receptor BI as a potential screening candidate for congenital primary adrenal insufficiency in humans. 61
32369415 2020
31
[Modified-release hydrocortisone for glucocorticoid deficiency]. 61
32394073 2020
32
The management of glucocorticoid deficiency: Current and future perspectives. 61
32145273 2020
33
Glucocorticoids Reverse Diluted Hyponatremia Through Inhibiting Arginine Vasopressin Pathway in Heart Failure Rats. 61
32390535 2020
34
GDF15 Is Elevated in Conditions of Glucocorticoid Deficiency and Is Modulated by Glucocorticoid Replacement. 61
31853550 2020
35
Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia. 61
32190901 2020
36
Current Insights Into Adrenal Insufficiency in the Newborn and Young Infant. 61
33381483 2020
37
Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected. 61
32903448 2020
38
Tyrosine Kinase Inhibitors' Newly Reported Endocrine Side Effect: Pazopanib-Induced Primary Adrenal Insufficiency in a Patient With Metastatic Renal Cell Cancer. 61
32583692 2020
39
Rare Bilateral Adrenal Haemorrhage with Addisonian Crisis: When Risk Factors Come in Droves. 61
32832170 2020
40
The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants. 61
32952553 2020
41
Hypophysitis: An update on the novel forms, diagnosis and management of disorders of pituitary inflammation. 61
31866206 2019
42
Familial hypogammaglobulinemia with high RTE and naïve T lymphocytes. 61
31468084 2019
43
CLINICAL COURSE OF A UNIQUE CASE OF ALLGROVE SYNDROME AND CHALLENGES OF HYPOGLYCEMIA MANAGEMENT. 61
31967070 2019
44
ELECTROCARDIOGRAM CHANGES IN ADDISON DISEASE: POTENTIAL CLINICAL MARKER FOR ADRENAL CRISIS. 61
31967059 2019
45
Structure and mechanism of mitochondrial proton-translocating transhydrogenase. 61
31462775 2019
46
Familial glucocorticoid deficiency presenting with hyperpigmentation, gigantism, and motor development delay: a case report. 61
31481085 2019
47
Management of congenital adrenal hyperplasia: beyond conventional glucocorticoid therapy. 61
31295195 2019
48
The incidence of adrenal crisis in the postoperative period of HPA axis insufficiency after surgical treatment for Cushing's syndrome. 61
31167165 2019
49
ACTH signalling and adrenal development: lessons from mouse models. 61
31189126 2019
50
Posterior pituitary dysfunction following traumatic brain injury: review. 61
30334138 2019

Variations for Familial Glucocorticoid Deficiency

ClinVar genetic disease variations for Familial Glucocorticoid Deficiency:

6 (show top 50) (show all 206)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MC2R NM_000529.2(MC2R):c.634del (p.Arg212fs) Deletion Pathogenic 492870 rs1226345778 GRCh37: 18:13884884-13884884
GRCh38: 18:13884885-13884885
2 MC2R NM_000529.2(MC2R):c.433C>T (p.Arg145Cys) SNV Pathogenic 492866 rs139218324 GRCh37: 18:13885085-13885085
GRCh38: 18:13885086-13885086
3 MC2R NM_000529.2(MC2R):c.560del (p.Val187fs) Deletion Pathogenic 492868 rs1555619406 GRCh37: 18:13884958-13884958
GRCh38: 18:13884959-13884959
4 MC2R NM_000529.2(MC2R):c.573C>A (p.Cys191Ter) SNV Pathogenic 492869 rs762692123 GRCh37: 18:13884945-13884945
GRCh38: 18:13884946-13884946
5 MC2R NM_000529.2(MC2R):c.221G>T (p.Ser74Ile) SNV Pathogenic 3258 rs104894658 GRCh37: 18:13885297-13885297
GRCh38: 18:13885298-13885298
6 MC2R NM_000529.2(MC2R):c.601C>T (p.Arg201Ter) SNV Pathogenic 3259 rs104894659 GRCh37: 18:13884917-13884917
GRCh38: 18:13884918-13884918
7 MC2R NM_000529.2(MC2R):c.360C>G (p.Ser120Arg) SNV Pathogenic 3260 rs104894656 GRCh37: 18:13885158-13885158
GRCh38: 18:13885159-13885159
8 MC2R NM_000529.2(MC2R):c.382C>T (p.Arg128Cys) SNV Pathogenic 3261 rs104894657 GRCh37: 18:13885136-13885136
GRCh38: 18:13885137-13885137
9 MC2R NM_000529.2(MC2R):c.319G>A (p.Asp107Asn) SNV Pathogenic 3262 rs104894661 GRCh37: 18:13885199-13885199
GRCh38: 18:13885200-13885200
10 MC2R MC2R, 1-BP INS, 1347A Insertion Pathogenic 3263 GRCh37:
GRCh38:
11 MC2R NM_000529.2(MC2R):c.752G>T (p.Cys251Phe) SNV Pathogenic 3264 rs104894662 GRCh37: 18:13884766-13884766
GRCh38: 18:13884767-13884767
12 MC2R NM_000529.2(MC2R):c.409C>T (p.Arg137Trp) SNV Pathogenic 3265 rs104894660 GRCh37: 18:13885109-13885109
GRCh38: 18:13885110-13885110
13 MC2R NM_000529.2(MC2R):c.761A>G (p.Tyr254Cys) SNV Pathogenic 3266 rs28940892 GRCh37: 18:13884757-13884757
GRCh38: 18:13884758-13884758
14 MC2R NM_000529.2(MC2R):c.376G>T (p.Ala126Ser) SNV Pathogenic 18425 rs267607231 GRCh37: 18:13885142-13885142
GRCh38: 18:13885143-13885143
15 NNT NM_182977.3(NNT):c.1598C>T (p.Ala533Val) SNV Pathogenic 35538 rs387907232 GRCh37: 5:43649402-43649402
GRCh38: 5:43649300-43649300
16 NNT NM_182977.3(NNT):c.600-1del Deletion Pathogenic 35539 rs786205344 GRCh37: 5:43619133-43619133
GRCh38: 5:43619031-43619031
17 NNT NM_182977.3(NNT):c.2930T>C (p.Leu977Pro) SNV Pathogenic 35540 rs387907233 GRCh37: 5:43700274-43700274
GRCh38: 5:43700172-43700172
18 NNT NM_182977.3(NNT):c.1107_1110del (p.Thr369_His370insTer) Deletion Pathogenic 35541 rs786205345 GRCh37: 5:43644719-43644722
GRCh38: 5:43644617-43644620
19 NNT NM_182977.3(NNT):c.3022G>C (p.Ala1008Pro) SNV Pathogenic 35543 rs387907234 GRCh37: 5:43702749-43702749
GRCh38: 5:43702647-43702647
20 NNT NM_182977.3(NNT):c.644T>C (p.Phe215Ser) SNV Pathogenic 265839 rs886039786 GRCh37: 5:43619178-43619178
GRCh38: 5:43619076-43619076
21 NNT NM_182977.3(NNT):c.385C>T (p.Arg129Ter) SNV Pathogenic 265843 rs886039789 GRCh37: 5:43615953-43615953
GRCh38: 5:43615851-43615851
22 NNT NM_182977.3(NNT):c.211C>T (p.Arg71Ter) SNV Pathogenic 265844 rs886039790 GRCh37: 5:43613069-43613069
GRCh38: 5:43612967-43612967
23 MC2R NM_000529.2(MC2R):c.221G>T (p.Ser74Ile) SNV Pathogenic 3258 rs104894658 GRCh37: 18:13885297-13885297
GRCh38: 18:13885298-13885298
24 MC2R NM_000529.2(MC2R):c.409C>T (p.Arg137Trp) SNV Pathogenic 3265 rs104894660 GRCh37: 18:13885109-13885109
GRCh38: 18:13885110-13885110
25 MC2R NM_000529.2(MC2R):c.410G>C (p.Arg137Pro) SNV Pathogenic 492865 rs1208417750 GRCh37: 18:13885108-13885108
GRCh38: 18:13885109-13885109
26 MRAP NM_178817.4(MRAP):c.106+1G>T SNV Pathogenic 1836 rs566223651 GRCh37: 21:33671389-33671389
GRCh38: 21:32299078-32299078
27 MRAP NM_178817.4(MRAP):c.106+1G>C SNV Pathogenic 1837 rs566223651 GRCh37: 21:33671389-33671389
GRCh38: 21:32299078-32299078
28 MRAP NM_178817.4(MRAP):c.106+1G>A SNV Pathogenic 1838 rs566223651 GRCh37: 21:33671389-33671389
GRCh38: 21:32299078-32299078
29 MRAP MRAP, IVS3, G DEL, +1 Deletion Pathogenic 1839 GRCh37:
GRCh38:
30 MRAP MRAP, IVS3, T INS, +3 Insertion Pathogenic 1840 GRCh37:
GRCh38:
31 MRAP-AS1 , MRAP NM_001285394.2(MRAP):c.-48del Deletion Pathogenic 1842 rs760615045 GRCh37: 21:33678972-33678972
GRCh38: 21:32306661-32306661
32 MRAP NM_001285394.2(MRAP):c.-72+5856_-72+5862del Deletion Pathogenic 1843 rs1569025178 GRCh37: 21:33671299-33671305
GRCh38: 21:32298988-32298994
33 NNT NM_182977.3(NNT):c.1259dup (p.His421fs) Duplication Pathogenic 218365 rs864309519 GRCh37: 5:43644870-43644871
GRCh38: 5:43644768-43644769
34 MRAP NM_001285394.2(MRAP):c.-72+5840A>G SNV Pathogenic 444067 rs1555897462 GRCh37: 21:33671283-33671283
GRCh38: 21:32298972-32298972
35 MRAP NM_178817.4(MRAP):c.106+1del Deletion Pathogenic 444068 rs1476574441 GRCh37: 21:33671389-33671389
GRCh38: 21:32299078-32299078
36 MC2R NM_000529.2(MC2R):c.424G>T (p.Val142Leu) SNV Pathogenic 444066 rs199950178 GRCh37: 18:13885094-13885094
GRCh38: 18:13885095-13885095
37 MC2R NM_000529.2(MC2R):c.702del (p.Phe235fs) Deletion Pathogenic 444063 rs1555619372 GRCh37: 18:13884816-13884816
GRCh38: 18:13884817-13884817
38 MC2R NM_000529.2(MC2R):c.674T>G (p.Leu225Arg) SNV Pathogenic 444064 rs1555619377 GRCh37: 18:13884844-13884844
GRCh38: 18:13884845-13884845
39 MRAP NM_178817.4(MRAP):c.3G>A (p.Met1Ile) SNV Pathogenic 1841 rs80358231 GRCh37: 21:33671285-33671285
GRCh38: 21:32298974-32298974
40 NNT NM_182977.3(NNT):c.3027T>G (p.Asn1009Lys) SNV Pathogenic 35542 rs370273690 GRCh37: 5:43702754-43702754
GRCh38: 5:43702652-43702652
41 MC2R NM_000529.2(MC2R):c.459dup (p.Ile154fs) Duplication Pathogenic 444065 rs1555619430 GRCh37: 18:13885058-13885059
GRCh38: 18:13885059-13885060
42 MRAP NM_178817.4(MRAP):c.3G>A (p.Met1Ile) SNV Pathogenic 1841 rs80358231 GRCh37: 21:33671285-33671285
GRCh38: 21:32298974-32298974
43 MC2R NM_000529.2(MC2R):c.459dup (p.Ile154fs) Duplication Pathogenic 444065 rs1555619430 GRCh37: 18:13885058-13885059
GRCh38: 18:13885059-13885060
44 NNT NM_182977.3(NNT):c.98dup (p.Leu33fs) Duplication Likely pathogenic 800942 rs1579966821 GRCh37: 5:43609389-43609390
GRCh38: 5:43609287-43609288
45 NNT NM_182977.3(NNT):c.598G>A (p.Gly200Ser) SNV Likely pathogenic 265842 rs886039788 GRCh37: 5:43616166-43616166
GRCh38: 5:43616064-43616064
46 NNT NM_182977.3(NNT):c.1575dup (p.Pro526fs) Duplication Likely pathogenic 930557 GRCh37: 5:43649378-43649379
GRCh38: 5:43649276-43649277
47 MC2R NM_000529.2(MC2R):c.465G>C (p.Trp155Cys) SNV Likely pathogenic 492867 rs1555619429 GRCh37: 18:13885053-13885053
GRCh38: 18:13885054-13885054
48 MC2R NM_000529.2(MC2R):c.437G>A (p.Arg146His) SNV Likely pathogenic 631794 rs758709668 GRCh37: 18:13885081-13885081
GRCh38: 18:13885082-13885082
49 MC2R NM_000529.2(MC2R):c.318C>T (p.Ile106=) SNV Uncertain significance 80762 rs147706299 GRCh37: 18:13885200-13885200
GRCh38: 18:13885201-13885201
50 MC2R NM_000529.2(MC2R):c.*1012T>A SNV Uncertain significance 326155 rs886053632 GRCh37: 18:13883612-13883612
GRCh38: 18:13883613-13883613

Expression for Familial Glucocorticoid Deficiency

Search GEO for disease gene expression data for Familial Glucocorticoid Deficiency.

Pathways for Familial Glucocorticoid Deficiency

Pathways related to Familial Glucocorticoid Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.27 STAR POMC NR0B1 MRAP MC2R HSD3B2
2 11.53 STAR POMC HSD3B2 CYP11A1
3
Show member pathways
11.51 POMC MC2R CYP11A1
4
Show member pathways
11.36 STAR POMC HSD3B2 CYP11A1
5 11.21 STAR HSD3B2 CYP11A1
6 11.19 POMC MC5R MC4R MC3R MC2R
7 10.73 POMC MC4R
8 10.63 POMC MC4R

GO Terms for Familial Glucocorticoid Deficiency

Biological processes related to Familial Glucocorticoid Deficiency according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 male gonad development GO:0008584 9.71 STAR REN NR0B1
2 regulation of blood pressure GO:0008217 9.63 REN POMC MC3R
3 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger GO:0007187 9.61 MC5R MC3R MC2R
4 steroid biosynthetic process GO:0006694 9.58 STAR HSD3B2 CYP11A1
5 response to immobilization stress GO:0035902 9.57 REN NR0B1
6 negative regulation of protein localization to plasma membrane GO:1903077 9.56 MRAP2 MRAP
7 response to corticosterone GO:0051412 9.55 STAR HSD3B2
8 energy reserve metabolic process GO:0006112 9.52 MRAP2 MC4R
9 regulation of feeding behavior GO:0060259 9.51 MC4R MC3R
10 C21-steroid hormone biosynthetic process GO:0006700 9.49 STAR CYP11A1
11 glucocorticoid biosynthetic process GO:0006704 9.48 HSD3B2 CYP11A1
12 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.46 MC5R MC4R MC3R MC2R
13 C21-steroid hormone metabolic process GO:0008207 9.37 HSD3B2 CYP11A1
14 negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0106072 9.32 MRAP2 MRAP
15 positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0106071 9.26 MRAP2 MRAP
16 regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0106070 8.96 MRAP2 MRAP
17 regulation of metabolic process GO:0019222 8.92 MC5R MC4R MC3R MC2R

Molecular functions related to Familial Glucocorticoid Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuropeptide binding GO:0042923 9.48 MC4R MC3R
2 hormone binding GO:0042562 9.46 MC5R MC4R
3 receptor regulator activity GO:0030545 9.43 MRAP2 MRAP
4 type 1 melanocortin receptor binding GO:0070996 9.43 POMC MRAP2 MRAP
5 melanocyte-stimulating hormone receptor activity GO:0004980 9.4 MC4R MC3R
6 type 5 melanocortin receptor binding GO:0031783 9.37 MRAP2 MRAP
7 type 4 melanocortin receptor binding GO:0031782 9.33 POMC MRAP2 MRAP
8 corticotropin hormone receptor binding GO:0031780 9.32 MRAP2 MRAP
9 type 3 melanocortin receptor binding GO:0031781 9.13 POMC MRAP2 MRAP
10 melanocortin receptor activity GO:0004977 8.92 MC5R MC4R MC3R MC2R

Sources for Familial Glucocorticoid Deficiency

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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