CBG DEFICIENCY
MCID: CRT046
MIFTS: 40

Corticosteroid-Binding Globulin Deficiency (CBG DEFICIENCY)

Categories: Endocrine diseases, Genetic diseases, Rare diseases
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Aliases & Classifications for Corticosteroid-Binding Globulin Deficiency

MalaCards integrated aliases for Corticosteroid-Binding Globulin Deficiency:

Name: Corticosteroid-Binding Globulin Deficiency 57 11 19 42 58 73 28 12 5 43 14 38 71
Transcortin Deficiency 57 11 19 42 58
Cbg Deficiency 57 11 19 42 73

Characteristics:


Inheritance:

Semi-dominant 58 , Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable phenotype
many patients are asymptomatic


Classifications:

Orphanet: 58  
Rare endocrine diseases


External Ids:

Disease Ontology 11 DOID:0090030
OMIM® 57 611489
MeSH 43 C565152
ICD10 31 E27.8
ICD10 via Orphanet 32 E27.8
UMLS via Orphanet 72 C1852529
Orphanet 58 ORPHA199247
UMLS 71 C1852529

Summaries for Corticosteroid-Binding Globulin Deficiency

GARD: 19 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 genetic changes 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.

MalaCards based summary: Corticosteroid-Binding Globulin Deficiency, also known as transcortin deficiency, is related to chronic fatigue syndrome and pituitary-dependent cushing's disease, 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 Metabolism of steroids and Glucocorticoid receptor regulatory network. Affiliated tissues include adrenal gland, liver and brain, and related phenotypes are hypotension and hypertension

MedlinePlus Genetics: 42 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.

Orphanet: 58 Corticosteroid-binding globulin deficiency is a rare, genetic, adrenal disease characterized by diminished corticosteroid-binding capacity associated with normal or low plasma corticosteroid-binding globulin concentration and reduced total plasma cortisol levels. Patients typically present chronic pain, fatigue and hypo/hypertension.

Disease Ontology: 11 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.

UniProtKB/Swiss-Prot: 73 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 62)
# Related Disease Score Top Affiliating Genes
1 chronic fatigue syndrome 30.0 POMC NR3C1
2 pituitary-dependent cushing's disease 29.8 POMC NR3C1 MC2R
3 conn's syndrome 29.1 SERPINA6 POMC NR3C1 MC2R HSD11B2
4 body mass index quantitative trait locus 11 29.1 SERPINA6 POMC NR3C1 MC2R HSD11B2
5 toxic shock syndrome 10.2
6 thyroid crisis 10.1 SERPINA7 POMC
7 euthyroid sick syndrome 10.1 SERPINA7 POMC
8 graves disease 1 10.1 SERPINA7 POMC
9 myxedema 10.1 SERPINA7 POMC
10 cortisone reductase deficiency 10.1 POMC HSD11B2
11 alzheimer disease 16 10.1 POMC NR3C1
12 apparent mineralocorticoid excess 10.1 POMC HSD11B2
13 mediastinal lipomatosis 10.1 POMC NR3C1
14 ectopic cushing syndrome 10.1 POMC NR3C1
15 ovarian serous adenofibroma 10.1 POMC NR3C1
16 acute stress disorder 10.1 POMC NR3C1
17 atypical depressive disorder 10.1 POMC NR3C1
18 nelson syndrome 10.1 POMC NR3C1
19 persistent fetal circulation syndrome 10.1 POMC HSD11B2
20 acth deficiency, isolated 10.1
21 proteasome-associated autoinflammatory syndrome 1 10.1
22 hyperinsulinism 10.1
23 abnormality of glucagon secretion 10.1 SERPINA7 NR3C1
24 skin atrophy 10.0 POMC NR3C1
25 acth-secreting pituitary adenoma 10.0 POMC NR3C1
26 waterhouse-friderichsen syndrome 10.0 POMC MC2R
27 endogenous depression 10.0 POMC NR3C1
28 adrenal rest tumor 10.0 POMC MC2R
29 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 10.0 POMC MC2R
30 glucocorticoid deficiency 1 10.0 POMC MC2R
31 ocular hypertension 10.0 SERPINA6 NR3C1
32 adrenal cortical hypofunction 10.0 POMC MC2R
33 acth-independent macronodular adrenal hyperplasia 10.0 POMC MC2R
34 adrenal hypoplasia, congenital 10.0 POMC MC2R
35 post-traumatic stress disorder 10.0 POMC NR3C1
36 achalasia-addisonianism-alacrima syndrome 10.0 POMC MC2R
37 primary pigmented nodular adrenocortical disease 10.0 POMC MC2R
38 hyperthyroidism 10.0 SERPINA7 SERPINA6 POMC
39 familial glucocorticoid deficiency 10.0 POMC MC2R
40 adrenal cortical adenoma 10.0 POMC MC2R
41 hypoadrenocorticism, familial 10.0 POMC MC2R
42 lennox-gastaut syndrome 10.0 SERPINA6 POMC
43 mccune-albright syndrome 9.9 POMC MC2R
44 carney complex variant 9.9 POMC MC2R
45 mental depression 9.9 POMC NR3C1
46 hyperandrogenism 9.9 POMC NR3C1
47 thyroid gland disease 9.9 SERPINA7 POMC
48 postpartum depression 9.9 POMC NR3C1 HSD11B2
49 adult syndrome 9.9 POMC NR3C1 HSD11B2
50 liddle syndrome 1 9.9 POMC NR3C1 HSD11B2

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:

30
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypotension 30 HP:0002615
2 hypertension 30 HP:0000822
3 fatigue 30 HP:0012378
4 abnormality of metabolism/homeostasis 30 HP:0001939
5 increased muscle fatiguability 30 HP:0003750

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Cardiovascular Vascular:
hypotension
hypertension

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 (Updated 08-Dec-2022)

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:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 8.92 HSD11B2 MC2R NR3C1 POMC

MGI Mouse Phenotypes related to Corticosteroid-Binding Globulin Deficiency:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.43 CYB561 HSD11B2 MC2R NR3C1 POMC SERPINA7
2 behavior/neurological MP:0005386 9.17 CYB561 ELANE HSD11B2 MC2R NR3C1 POMC

Drugs & Therapeutics for Corticosteroid-Binding Globulin Deficiency

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

Cochrane evidence based reviews: 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 28 SERPINA6

Anatomical Context for Corticosteroid-Binding Globulin Deficiency

Organs/tissues related to Corticosteroid-Binding Globulin Deficiency:

MalaCards : Adrenal Gland, Liver, Brain

Publications for Corticosteroid-Binding Globulin Deficiency

Articles related to Corticosteroid-Binding Globulin Deficiency:

(show all 36)
# 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. 62 57 5
17245537 2007
2
Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension. 62 57 5
11502797 2001
3
Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity. 57 5
10634411 2000
4
Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. 57 5
8212073 1993
5
Transcortin Leuven: a variant of human corticosteroid-binding globulin with decreased cortisol-binding affinity. 57 5
7061486 1982
6
Hereditary corticosteroid-binding globulin deficiency due to a missense mutation (Asp367Asn, CBG Lyon) in a Brazilian kindred. 62 5
12780753 2003
7
Marked elevation and cyclic variation of corticosteroid-binding globulin: an inherited abnormality? 57
2493032 1989
8
Idiopathic or genetic elevation of corticosteroid-binding globulin? 57
4969809 1968
9
Cortisol-binding capacity of plasma transcortin: a sex-linked trait? 57
6028282 1967
10
FAMILIAL DECREASE IN CORTICOSTEROID-BINDING GLOBULIN. 57
14320983 1965
11
Correction to: "Corticosteroid-Binding Globulin Deficiency Independently Predicts Mortality in Septic Shock". 62
35478012 2022
12
Corticosteroid-Binding Globulin Deficiency Independently Predicts Mortality in Septic Shock. 62
35152290 2022
13
Corticosteroid-binding-globulin (CBG)-deficient mice show high pY216-GSK3β and phosphorylated-Tau levels in the hippocampus. 62
33592009 2021
14
Corticosteroid-Binding Globulin is expressed in the adrenal gland and its absence impairs corticosterone synthesis and secretion in a sex-dependent manner. 62
31570737 2019
15
LIMITATIONS OF BASAL CORTISOL IN THE DIAGNOSIS OF CUSHING SYNDROME. 62
31967009 2019
16
Corticosteroid-Binding Globulin Deficiency Specifically Impairs Contextual and Recognition Memory Consolidation in Male Mice. 62
30904918 2019
17
SERUM FREE CORTISOL DURING GLUCAGON STIMULATION TEST IN HEALTHY SHORT-STATURED CHILDREN AND ADOLESCENTS. 62
29547045 2018
18
Altered lipid partitioning and glucocorticoid availability in CBG-deficient male mice with diet-induced obesity. 62
27323695 2016
19
Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice. 62
27153522 2016
20
Impact of corticosteroid-binding globulin deficiency on pregnancy and neonatal sex. 62
25695888 2015
21
Role of corticosteroid binding globulin in emotional reactivity sex differences in mice. 62
25244639 2014
22
Critical role of plasma corticosteroid-binding-globulin during stress to promote glucocorticoid delivery to the brain: impact on memory retrieval. 62
22930537 2012
23
Novel corticosteroid-binding globulin variant that lacks steroid binding activity. 62
20610591 2010
24
Corticosteroid-binding globulin: the clinical significance of altered levels and heritable mutations. 62
19643166 2010
25
Genotype-phenotype associations in understanding the role of corticosteroid-binding globulin in health and disease animal models. 62
19643164 2010
26
Plasma transcortin influences endocrine and behavioral stress responses in mice. 62
20022933 2010
27
Measurement of salivary cortisol with liquid chromatography-tandem mass spectrometry in patients undergoing dynamic endocrine testing. 62
19302583 2010
28
Validation of a simple method of estimating plasma free cortisol: role of cortisol binding to albumin. 62
18976646 2009
29
[Inherited corticosteroid-binding globulin (CBG) deficiency]. 62
16776267 2006
30
Plasma free cortisol fraction reflects levels of functioning corticosteroid-binding globulin. 62
15904907 2005
31
Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency. 62
12554596 2003
32
A case of cyclical Cushing's disease associated with corticosteroid-binding globulin deficiency: a rare pitfall in the diagnosis of Cushing's disease. 62
7581948 1995
33
[Congenital CBG deficiency]. 62
7757648 1993
34
Haplotypes in transcortin deficiency. 62
3742837 1986
35
Total deficiency of corticosteroid-binding globulin. 62
6499234 1984
36
Vitamin B-12 (cobalamin) deficiency: a heretofore undescribed control mechanism for plasma corticosteroid-binding globulin concentration in man. 62
6172443 1982

Variations for Corticosteroid-Binding Globulin Deficiency

ClinVar genetic disease variations for Corticosteroid-Binding Globulin Deficiency:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SERPINA6 NM_001756.4(SERPINA6):c.32G>A (p.Trp11Ter) SNV Pathogenic
16976 GRCh37: 14:94780954-94780954
GRCh38: 14:94314617-94314617
2 SERPINA6 NM_001756.4(SERPINA6):c.344T>A (p.Leu115His) SNV Pathogenic
16974 rs113418909 GRCh37: 14:94780642-94780642
GRCh38: 14:94314305-94314305
3 SERPINA6 NM_001756.4(SERPINA6):c.164_165del (p.Val55fs) DEL Likely Pathogenic
1077111 GRCh37: 14:94780821-94780822
GRCh38: 14:94314484-94314485
4 SERPINA6 NM_001756.4(SERPINA6):c.1165G>A (p.Asp389Asn) SNV Uncertain Significance
16975 rs28929488 GRCh37: 14:94770808-94770808
GRCh38: 14:94304471-94304471
5 SERPINA6 NM_001756.4(SERPINA6):c.539G>A (p.Gly180Glu) SNV Uncertain Significance
1029528 rs769978145 GRCh37: 14:94780447-94780447
GRCh38: 14:94314110-94314110

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

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 glucocorticoid metabolic process GO:0008211 9.1 SERPINA6 NR3C1 HSD11B2

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

# Name GO ID Score Top Affiliating Genes
1 steroid binding GO:0005496 9.1 SERPINA6 NR3C1 HSD11B2

Sources for Corticosteroid-Binding Globulin Deficiency

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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