SERPINA6
protein-codingserpin family A member 6, the group of Serpin peptidase inhibitors
Gene summary
This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]
- CBG
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012675
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: Unknown
Disease ID:MONDO:0012675
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: SD
Disease ID:MONDO:0012675
Submitter: PanelApp Australia
Inheritance Pattern: SD
Disease ID:MONDO:0012675
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0012675
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SERPINA6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001756.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | 1 | 9 | |||
| missense | 1 | 68 | 3 | 72 | ||
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 2 | 72 | 11 | 1 | 87 |
Highest pathogenic variant AF is 0.00035811425
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001747.3 | 4 | MANE Select | |
| Ensembl | ENSP00000342850.3 | 4 | MANE Select | |
| Ensembl | ENSP00000451045.1 | 2 | Standard | |
| Ensembl | ENSP00000452018.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glucocorticoid Pathway (Peripheral Tissue), Pharmacodynamics
Biological Process
- glucocorticoid metabolic process
- negative regulation of endopeptidase activity
Molecular Function
- serine-type endopeptidase inhibitor activity
- steroid binding
Cellular Component
- extracellular space
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000341584
- Coding exons
- 4
- Length
- 19147
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125746
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.662 | 244 | 217 | 1.13 | 0.0000124 | 2685 |
| Missense (PolyPhen) | 59 | 58.942 | 1.001 | 830 | ||
| Synonymous | -0.647 | 97 | 89.2 | 1.09 | 0.00000537 | 800 |
| Loss of Function | 0.367 | 10 | 11.3 | 0.882 | 4.99e-7 | 142 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000070 | 0.000070 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species. {ECO:0000269|PubMed:18513745}.;
- Disease
- DISEASE: Corticosteroid-binding globulin deficiency (CBG deficiency) [MIM:611489]: 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. {ECO:0000269|PubMed:10634411, ECO:0000269|PubMed:1504007, ECO:0000269|PubMed:17245537, ECO:0000269|PubMed:8212073}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.212
Intolerance Scores
- LoFtool
- 0.173
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.160
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |