SERPINF2

Chr 17AR

serpin family F member 2

Also known as: A2AP, AAP, ALPHA-2-PI, API, PLI, alpha2AP

NCBI Gene: 5345ENSG00000167711UniProt: P08697

This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Alpha-2-plasmin inhibitor deficiencyMIM #262850
AR
200
ClinVar variants
84
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— SERPINF2
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Gene-Disease Validity (ClinGen)
alpha-2-plasmin inhibitor deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
84 Pathogenic / Likely Pathogenic· 75 VUS of 200 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.63LOEUF
pLI 0.014
Z-score 2.83
OE 0.33 (0.19–0.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.23Z-score
OE missense 0.80 (0.71–0.89)
229 obs / 287.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.19–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.71–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 7 / 21.0Missense obs/exp: 229 / 287.8Syn Z: -0.13

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic73
Likely Pathogenic11
VUS75
Likely Benign26
Benign11
Conflicting4
73
Pathogenic
11
Likely Pathogenic
75
VUS
26
Likely Benign
11
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
70
0
73
Likely Pathogenic
1
0
10
0
11
VUS
0
59
16
0
75
Likely Benign
0
7
7
12
26
Benign
0
3
6
2
11
Conflicting
—4
Total37010914200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SERPINF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Alpha-2-plasmin inhibitor deficiency

MIM #262850

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare inherited coagulation and fibrinolytic defects that challenge diagnostic laboratories.
Mathews N et al.·Int J Lab Hematol
2023Review
Laboratory diagnosis of congenital and acquired coagulopathies, including challenging-to-diagnose rare bleeding disorders.
Al Dawood R et al.·Pathology
2025Review
Alterations in the kallikrein-kinin system predict death after heart transplant.
Giangreco NP et al.·Sci Rep
2022
Identification and Validation of a Novel Prognostic Signature of Gastric Cancer Based on Seven Complement System-Related Genes: An Integrated Analysis.
Zhang J et al.·Crit Rev Eukaryot Gene Expr
2025
Sialyltransferase-related genes as predictive factors for therapeutic response and prognosis in cervical cancer.
Shao J et al.·PeerJ
2025
Unveiling the levels and significance of different serpin family proteins in aqueous humor dynamics.
Williams E et al.·BMC Ophthalmol
2025
Associations of minor histocompatibility antigens with outcomes following allogeneic hematopoietic cell transplantation.
Jadi O et al.·Am J Hematol
2023
Study on Preclinical Safety and Toxic Mechanism of Human Umbilical Cord Mesenchymal Stem Cells in F344RG Rats.
Hao X et al.·Stem Cell Rev Rep
2024Functional
Exploring novel independent prognostic biomarkers for hepatocellular carcinoma based on TCGA and GEO databases.
Hou M·Medicine (Baltimore)
2022
Abnormal fibrinolysis recognized by thromboelastography in a case of severe bleeding with normal coagulation and platelet function, leads to detection of a novel SERPINF2 variant causing severe alpha-2-antiplasmin deficiency.
Egan G et al.·Br J Haematol
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Ischemic Stroke

Strategy for Improving Stroke Treatment Response

RECRUITING
NCT05948566Phase PHASE2Translational Sciences, Inc.Started 2024-03-18
TS23

External Resources

Links to major genomics databases and tools