CBG DEFICIENCY
MCID: CRT046
MIFTS: 38

Corticosteroid-Binding Globulin Deficiency (CBG DEFICIENCY)

Categories: Blood diseases, Endocrine diseases, Genetic diseases, Liver diseases, Rare diseases

Aliases & Classifications for Corticosteroid-Binding Globulin Deficiency

MalaCards integrated aliases for Corticosteroid-Binding Globulin Deficiency:

Name: Corticosteroid-Binding Globulin Deficiency 56 12 52 25 58 73 29 13 6 15 39 71
Transcortin Deficiency 56 12 52 25 58
Cbg Deficiency 56 12 52 25 73
Corticosteroid-Binding Globulin Deficiency 36

Characteristics:

Orphanet epidemiological data:

58
corticosteroid-binding globulin deficiency
Inheritance: Semi-dominant;

OMIM:

56
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable phenotype
many patients are asymptomatic


HPO:

31
corticosteroid-binding globulin deficiency:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:0090030
OMIM 56 611489
KEGG 36 H01163
ICD10 32 E27.8
ICD10 via Orphanet 33 E27.8
UMLS via Orphanet 72 C1852529
Orphanet 58 ORPHA199247
UMLS 71 C1852529

Summaries for Corticosteroid-Binding Globulin Deficiency

NIH Rare Diseases : 52 Corticosteroid -binding globulin deficiency is a genetic disorder characterized by extreme tiredness (fatigue), particularly after physical exertion, and low blood pressure (hypotension). Corticosteroid-binding globulin (CBG) is a protein primarily produced in the liver that attaches to cortisol , a hormone with numerous functions, including maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. When cortisol is needed in the body, CBG delivers the cortisol where it is needed and releases it. Signs and symptoms of CBG deficiency vary. While some individuals may experience no symptoms, others are found to have a fatty liver and chronic pain. Some people with CBG deficiency also have chronic fatigue syndrome . CGB deficiency is caused by mutations in the SERPINA6 gene . The SERPINA6 gene is commonly also referred to as the CBG gene. Both autosomal dominant and autosomal recessive inheritance have been reported. While there is still no cure, treatment options will depend on the type and severity of symptoms present and may involve several specialists.

MalaCards based summary : Corticosteroid-Binding Globulin Deficiency, also known as transcortin deficiency, is related to chronic fatigue syndrome and body mass index quantitative trait locus 11, and has symptoms including fatigue and generalized fatigue. An important gene associated with Corticosteroid-Binding Globulin Deficiency is SERPINA6 (Serpin Family A Member 6), and among its related pathways/superpathways are Aldosterone synthesis and secretion and Diseases of metabolism. Affiliated tissues include liver and adrenal gland, and related phenotypes are fatigue and abnormality of metabolism/homeostasis

Disease Ontology : 12 An adrenal gland disease characterized by decreased levels of serum corticosteroid-binding globulin and cortisol, and in some cases hypo- or hypertension, and muscle fatigue that has material basis in heterozygous or homozygous mutation in the SERPINA6 gene on chromosome 14q32.

Genetics Home Reference : 25 Corticosteroid-binding globulin deficiency is a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion. Many people with this condition have unusually low blood pressure (hypotension). Some affected individuals have a fatty liver or experience chronic pain, particularly in their muscles. These features vary among affected individuals, even those within the same family. Many people with corticosteroid-binding globulin deficiency have only one or two of these features; others have no signs and symptoms of the disorder and are only diagnosed after a relative is found to be affected. Some people with corticosteroid-binding globulin deficiency also have a condition called chronic fatigue syndrome. The features of chronic fatigue syndrome are prolonged fatigue that interferes with daily activities, as well as general symptoms, such as sore throat or headaches.

KEGG : 36 Corticosteroid-binding globulin (CBG) deficiency is a rare autosomal recessive disorder associated with hypotension and fatigue. CBG is the main transport protein for glucocorticoids in blood and only a few causative genetic variants in human CBG (SERPINA6) gene have been described.

UniProtKB/Swiss-Prot : 73 Corticosteroid-binding globulin deficiency: Extremely rare hereditary disorder characterized by reduced corticosteroid-binding capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels associated with hypo/hypertension and muscle fatigue.

More information from OMIM: 611489

Related Diseases for Corticosteroid-Binding Globulin Deficiency

Diseases related to Corticosteroid-Binding Globulin Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 60)
# Related Disease Score Top Affiliating Genes
1 chronic fatigue syndrome 29.8 POMC NR3C1
2 body mass index quantitative trait locus 11 28.3 STAR SERPINA6 POMC NR3C1 MC2R
3 alzheimer disease 16 10.2 POMC NR3C1
4 ovarian serous adenofibroma 10.1 POMC NR3C1
5 pituitary-dependent cushing's disease 10.1 POMC NR3C1
6 atypical depressive disorder 10.1 POMC NR3C1
7 nelson syndrome 10.1 POMC NR3C1
8 acute stress disorder 10.1 POMC NR3C1
9 ocular hypertension 10.1 SERPINA6 NR3C1
10 acth-secreting pituitary adenoma 10.1 POMC NR3C1
11 abnormality of glucagon secretion 10.1 SERPINA7 NR3C1
12 apparent mineralocorticoid excess 10.1 POMC NR3C1
13 hyperaldosteronism, familial, type i 10.1 POMC NR3C1
14 subacute thyroiditis 10.1 SERPINA7 SERPINA6
15 adult syndrome 10.1 POMC NR3C1
16 postpartum depression 10.1 POMC NR3C1
17 acute thyroiditis 10.1 SERPINA7 POMC
18 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 10.0 STAR POMC
19 endogenous depression 10.0 POMC NR3C1
20 euthyroid sick syndrome 10.0 SERPINA7 POMC
21 graves disease 1 10.0 SERPINA7 POMC
22 myxedema 10.0 SERPINA7 POMC
23 proteasome-associated autoinflammatory syndrome 1 10.0
24 hyperinsulinism 10.0
25 mental depression 10.0 POMC NR3C1
26 hypokalemia 10.0 POMC NR3C1
27 newborn respiratory distress syndrome 9.9 NR3C1 ELANE
28 hyperandrogenism 9.9 POMC NR3C1
29 disorders of sexual development 9.9 STAR POMC
30 alpha-1-antitrypsin deficiency 9.9 SERPINA6 ELANE
31 waterhouse-friderichsen syndrome 9.8 POMC MC2R
32 adrenal rest tumor 9.8 POMC MC2R
33 glucocorticoid deficiency 1 9.8 POMC MC2R
34 thyroid gland disease 9.8 SERPINA7 POMC
35 hyperthyroidism 9.8 SERPINA7 SERPINA6 POMC
36 acth-independent macronodular adrenal hyperplasia 9.8 POMC MC2R
37 pseudohermaphroditism 9.8 STAR POMC NR3C1
38 adrenal cortical carcinoma 9.8 POMC MC2R
39 adrenal cortical adenoma 9.8 POMC MC2R
40 carney complex variant 9.7 POMC MC2R
41 46,xy sex reversal 2 9.7 STAR MC2R
42 adrenal carcinoma 9.7 STAR POMC
43 adrenocortical carcinoma, hereditary 9.7 STAR MC2R
44 adrenal adenoma 9.7 POMC MC2R
45 turner syndrome 9.7 SERPINA7 POMC
46 post-traumatic stress disorder 9.6 POMC NR3C1
47 primary pigmented nodular adrenocortical disease 9.5 POMC NR3C1 MC2R
48 steroid inherited metabolic disorder 9.5 STAR POMC MC2R
49 adrenal cortical hypofunction 9.5 STAR POMC MC2R
50 adrenal hypoplasia, congenital 9.5 STAR POMC MC2R

Graphical network of the top 20 diseases related to Corticosteroid-Binding Globulin Deficiency:



Diseases related to Corticosteroid-Binding Globulin Deficiency

Symptoms & Phenotypes for Corticosteroid-Binding Globulin Deficiency

Human phenotypes related to Corticosteroid-Binding Globulin Deficiency:

31
# Description HPO Frequency HPO Source Accession
1 fatigue 31 HP:0012378
2 abnormality of metabolism/homeostasis 31 HP:0001939
3 hypertension 31 HP:0000822
4 hypotension 31 HP:0002615
5 increased muscle fatiguability 31 HP:0003750

Symptoms via clinical synopsis from OMIM:

56
Cardiovascular Vascular:
hypertension
hypotension

Laboratory Abnormalities:
decreased serum cortisol
decreased cortisol-binding globulin
normal free urinary cortisol
normal acth

Metabolic Features:
generalized fatigue

Muscle Soft Tissue:
muscle fatigue

Clinical features from OMIM:

611489

UMLS symptoms related to Corticosteroid-Binding Globulin Deficiency:


fatigue, generalized fatigue

GenomeRNAi Phenotypes related to Corticosteroid-Binding Globulin Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 8.92 MC2R NR3C1 POMC STAR

Drugs & Therapeutics for Corticosteroid-Binding Globulin Deficiency

Search Clinical Trials , NIH Clinical Center for Corticosteroid-Binding Globulin Deficiency

Genetic Tests for Corticosteroid-Binding Globulin Deficiency

Genetic tests related to Corticosteroid-Binding Globulin Deficiency:

# Genetic test Affiliating Genes
1 Corticosteroid-Binding Globulin Deficiency 29 SERPINA6

Anatomical Context for Corticosteroid-Binding Globulin Deficiency

MalaCards organs/tissues related to Corticosteroid-Binding Globulin Deficiency:

40
Liver, Adrenal Gland

Publications for Corticosteroid-Binding Globulin Deficiency

Articles related to Corticosteroid-Binding Globulin Deficiency:

(show all 15)
# Title Authors PMID Year
1
Haploinsufficiency of the SERPINA6 gene is associated with severe muscle fatigue: A de novo mutation in corticosteroid-binding globulin deficiency. 61 56 6
17245537 2007
2
Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension. 61 6 56
11502797 2001
3
Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity. 56 6
10634411 2000
4
Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. 56 6
8212073 1993
5
Transcortin Leuven: a variant of human corticosteroid-binding globulin with decreased cortisol-binding affinity. 6 56
7061486 1982
6
Hereditary corticosteroid-binding globulin deficiency due to a missense mutation (Asp367Asn, CBG Lyon) in a Brazilian kindred. 6 61
12780753 2003
7
Marked elevation and cyclic variation of corticosteroid-binding globulin: an inherited abnormality? 56
2493032 1989
8
Idiopathic or genetic elevation of corticosteroid-binding globulin? 56
4969809 1968
9
FAMILIAL DECREASE IN CORTICOSTEROID-BINDING GLOBULIN. 56
14320983 1965
10
Corticosteroid-Binding Globulin Deficiency Specifically Impairs Contextual and Recognition Memory Consolidation in Male Mice. 61
30904918 2019
11
Impact of corticosteroid-binding globulin deficiency on pregnancy and neonatal sex. 61
25695888 2015
12
Plasma transcortin influences endocrine and behavioral stress responses in mice. 61
20022933 2010
13
Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency. 61
12554596 2003
14
A case of cyclical Cushing's disease associated with corticosteroid-binding globulin deficiency: a rare pitfall in the diagnosis of Cushing's disease. 61
7581948 1995
15
Haplotypes in transcortin deficiency. 61
3742837 1986

Variations for Corticosteroid-Binding Globulin Deficiency

ClinVar genetic disease variations for Corticosteroid-Binding Globulin Deficiency:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SERPINA6 SERPINA6, 121G-ASNV Pathogenic 16976
2 SERPINA6 NM_001756.4(SERPINA6):c.1165G>A (p.Asp389Asn)SNV Pathogenic/Likely pathogenic 16975 rs28929488 14:94770808-94770808 14:94304471-94304471
3 SERPINA6 NM_001756.4(SERPINA6):c.344T>A (p.Leu115His)SNV Uncertain significance 16974 rs113418909 14:94780642-94780642 14:94314305-94314305

UniProtKB/Swiss-Prot genetic disease variations for Corticosteroid-Binding Globulin Deficiency:

73
# Symbol AA change Variation ID SNP ID
1 SERPINA6 p.Leu115His VAR_007111 rs113418909
2 SERPINA6 p.Asp389Asn VAR_016223 rs28929488

Expression for Corticosteroid-Binding Globulin Deficiency

Search GEO for disease gene expression data for Corticosteroid-Binding Globulin Deficiency.

Pathways for Corticosteroid-Binding Globulin Deficiency

Pathways related to Corticosteroid-Binding Globulin Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.03 STAR SERPINA7 POMC MC2R
2
Show member pathways
11.34 POMC MC2R
3 11.29 STAR POMC
4
Show member pathways
11.2 STAR POMC
5 11.07 POMC NR3C1
6 9.62 SERPINA6 NR3C1

GO Terms for Corticosteroid-Binding Globulin Deficiency

Biological processes related to Corticosteroid-Binding Globulin Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to transforming growth factor beta stimulus GO:0071560 9.16 STAR NR3C1
2 cellular response to dexamethasone stimulus GO:0071549 8.96 STAR NR3C1
3 glucocorticoid metabolic process GO:0008211 8.62 STAR SERPINA6

Molecular functions related to Corticosteroid-Binding Globulin Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 serine-type endopeptidase inhibitor activity GO:0004867 9.16 SERPINA7 SERPINA6
2 lipid binding GO:0008289 9.13 STAR SERPINA6 NR3C1
3 steroid binding GO:0005496 8.62 SERPINA6 NR3C1

Sources for Corticosteroid-Binding Globulin Deficiency

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
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