SERPINA4
protein-codingserpin family A member 4, the group of Serpin peptidase inhibitors
Gene summary
Predicted to enable serine-type endopeptidase inhibitor activity. Located in extracellular exosome and obsolete extracellular space. Biomarker of diabetic retinopathy. [provided by Alliance of Genome Resources, Jun 2026]
- PI4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.5 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 SERPINA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006215.4. 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 | 1 | 1 | 2 | |||
| missense | 80 | 7 | 1 | 88 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 81 | 7 | 2 | 90 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006206.2 | 4 | MANE Select | |
| Ensembl | ENSP00000450838.1 | 4 | MANE Select | |
| RefSeq | NP_001275961.1 | 5 | Standard | |
| RefSeq | NP_001275962.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Platelet degranulation
- Response to elevated platelet cytosolic Ca2+
- Platelet activation, signaling and aggregation
- Hemostasis
Biological Process
- platelet degranulation
- negative regulation of endopeptidase activity
Molecular Function
- serine-type endopeptidase inhibitor activity
Cellular Component
- extracellular region
- extracellular space
- platelet dense granule lumen
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000557004
- Coding exons
- 4
- Length
- 8823
- Individuals with no LoFs
- 125552
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 196
- Defined
- 125748
- p
- 0.000780
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.678 | 277 | 247 | 1.12 | 0.0000149 | 2814 |
| Missense (PolyPhen) | 86 | 64.549 | 1.3323 | 892 | ||
| Synonymous | -1.31 | 127 | 110 | 1.16 | 0.00000741 | 856 |
| Loss of Function | -0.149 | 12 | 11.5 | 1.05 | 5.54e-7 | 143 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00069 | 0.00069 | rare |
| Ashkenazi Jewish | 0.0044 | 0.0044 | notable |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0.00060 | 0.00060 | rare |
| European (Non-Finnish) | 0.00071 | 0.00071 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits human amidolytic and kininogenase activities of tissue kallikrein. Inhibition is achieved by formation of an equimolar, heat- and SDS-stable complex between the inhibitor and the enzyme, and generation of a small C-terminal fragment of the inhibitor due to cleavage at the reactive site by tissue kallikrein. {ECO:0000269|PubMed:8227002}.;
Recessive Scores
- pRec
- 0.239
Intolerance Scores
- RVIS EVS
- -0.75
- RVIS percentile EVS
- 13.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.568
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |