SERPINB1
protein-codingserpin family B member 1, the group of Serpin peptidase inhibitors
Gene summary
The protein encoded by this gene is a member of the serpin family of proteinase inhibitors. Members of this family maintain homeostasis by neutralizing overexpressed proteinase activity through their function as suicide substrates. This protein inhibits the neutrophil-derived proteinases neutrophil elastase, cathepsin G, and proteinase-3 and thus protects tissues from damage at inflammatory sites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
- ELANH2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SERPINB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030666.4. 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 | 2 | 1 | 3 | |||
| missense | 59 | 3 | 2 | 64 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 62 | 3 | 3 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_109591.1 | 6 | MANE Select | |
| Ensembl | ENSP00000370115.5 | 6 | MANE Select | |
| Ensembl | ENSP00000548965.1 | 6 | Standard | |
| Ensembl | ENSP00000548965.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amoebiasis - Homo sapiens (human)
- Vitamin D Receptor Pathway
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- negative regulation of endopeptidase activity
- neutrophil degranulation
Molecular Function
- serine-type endopeptidase inhibitor activity
Cellular Component
- extracellular region
- extracellular space
- membrane
- secretory granule lumen
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380739
- Coding exons
- 6
- Length
- 9675
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125748
- p
- 0.0000994
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.794 | 178 | 210 | 0.846 | 0.0000115 | 2509 |
| Missense (PolyPhen) | 43 | 62.575 | 0.68717 | 841 | ||
| Synonymous | 0.348 | 85 | 89.2 | 0.953 | 0.00000570 | 715 |
| Loss of Function | 0.258 | 12 | 13.0 | 0.923 | 5.44e-7 | 182 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000098 | 0.000088 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3. Also functions as a potent intracellular inhibitor of granzyme H. {ECO:0000269|PubMed:11747453}.;
Recessive Scores
- pRec
- 0.652
Intolerance Scores
- LoFtool
- 0.290
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.734
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |