SERPINA5
protein-codingserpin family A member 5, the group of Serpin peptidase inhibitors
Gene summary
The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. This family member is a glycoprotein that can inhibit several serine proteases, including protein C and various plasminogen activators and kallikreins, and it thus plays diverse roles in hemostasis and thrombosis in multiple organs. [provided by RefSeq, Aug 2012]
- PLANH3
- PCI
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.7 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 SERPINA5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000624.6. 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 | 1 | 1 | 2 | |||
| missense | 75 | 4 | 1 | 80 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 80 | 4 | 2 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000615.3 | 4 | MANE Select | |
| Ensembl | ENSP00000333203.7 | 4 | MANE Select | |
| Ensembl | ENSP00000451215.1 | 1 | Standard | |
| Ensembl | ENSP00000450837.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Complement and coagulation cascades - Homo sapiens (human)
- Dengue-2 Interactions with Complement and Coagulation Cascades
- Complement and Coagulation Cascades
- Intrinsic Pathway of Fibrin Clot Formation
- Hemostasis
Biological Process
- lipid transport
- spermatogenesis
- fusion of sperm to egg plasma membrane involved in single fertilization
- blood coagulation
- negative regulation of endopeptidase activity
Molecular Function
- retinoic acid binding
- protease binding
- serine-type endopeptidase inhibitor activity
- protein binding
- glycosaminoglycan binding
Cellular Component
- acrosomal membrane
- extracellular region
- extracellular space
- external side of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329597
- Coding exons
- 4
- Length
- 31679
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.24 | 289 | 236 | 1.23 | 0.0000132 | 2693 |
| Missense (PolyPhen) | 90 | 76.153 | 1.1818 | 934 | ||
| Synonymous | -1.69 | 121 | 99.6 | 1.21 | 0.00000602 | 793 |
| Loss of Function | -0.296 | 12 | 10.9 | 1.10 | 4.64e-7 | 132 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00016 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and proinflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary- type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue-and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid. {ECO:0000269|PubMed:10340997, ECO:0000269|PubMed:11722589, ECO:0000269|PubMed:14696115, ECO:0000269|PubMed:15140131, ECO:0000269|PubMed:15328353, ECO:0000269|PubMed:15853774, ECO:0000269|PubMed:1725227, ECO:0000269|PubMed:18467335, ECO:0000269|PubMed:2844223, ECO:0000269|PubMed:3501295, ECO:0000269|PubMed:6323392, ECO:0000269|PubMed:7521127, ECO:0000269|PubMed:7548057, ECO:0000269|PubMed:8536714, ECO:0000269|PubMed:8665956, ECO:0000269|PubMed:9473218, ECO:0000269|PubMed:9510955, ECO:0000269|PubMed:9556620}.;
Recessive Scores
- pRec
- 0.314
Intolerance Scores
- LoFtool
- 0.0590
- RVIS EVS
- 0.62
- RVIS percentile EVS
- 83.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.572
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |