Alpha-2-plasmin inhibitor deficiency

Summary

Alpha-2-plasmin inhibitor deficiency (MONDO:0009883) is a disease caused by SERPINF2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SERPINF2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 4
• Phenotypes (HPO): 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0001934	Persistent bleeding after trauma	Very frequent (80-99%)
HP:0005261	Joint hemorrhage	Very frequent (80-99%)
HP:0000790	Hematuria	Frequent (30-79%)
HP:0001892	Abnormal bleeding	Frequent (30-79%)
HP:0012151	Hemothorax	Frequent (30-79%)
HP:0012233	Intramuscular hematoma	Frequent (30-79%)
HP:0040247	Reduced euglobulin clot lysis time	Frequent (30-79%)
HP:0000225	Gingival bleeding	Occasional (5-29%)
HP:0000978	Bruising susceptibility	Occasional (5-29%)
HP:0002170	Intracranial hemorrhage	Occasional (5-29%)
HP:0002653	Bone pain	Occasional (5-29%)
HP:0011884	Abnormal umbilical stump bleeding	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	alpha-2-plasmin inhibitor deficiency
Mondo ID	MONDO:0009883
MeSH	C537777
OMIM	262850
Orphanet	79
DOID	DOID:0060601
ICD-11	688627594
SNOMED CT	716746003
UMLS	C2752081
MedGen	414178
GARD	0000731
Is cancer (heuristic)	no

Also known as: alpha-2-plasmin inhibitor deficiency · anti-plasmin deficiency, congenital · antiplasmin deficiency, congenital · plasmin inhibitor deficiency

Data availability: 4 ClinVar variants · 7 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › alpha-2-plasmin inhibitor deficiency

Related subtypes (27): factor XIII deficiency, factor VII deficiency, factor X deficiency, thrombophilia due to activated protein C resistance, hypoplasminogenemia, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, Tatsumi factor deficiency, East Texas bleeding disorder, inherited prekallikrein deficiency, congenital plasminogen activator inhibitor type 1 deficiency, thrombomodulin-related bleeding disorder, congenital vitamin K-dependent coagulation factors deficiency, hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, hemophilia, factor V deficiency, acquired coagulation factor deficiency, von Willebrand disease (hereditary or acquired), factor V short isoforms-related bleeding disorder, factor V amsterdam bleeding disorder, factor V atlanta bleeding disorder, combined deficiency of factor VII and factor X, plasminogen deficiency, type II, dysplasminogenemia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
274	NM_000934.4(SERPINF2):c.1437dup (p.Met480fs)	SERPINF2	Pathogenic	no assertion criteria provided
275	NM_000934.4(SERPINF2):c.525AGA[1] (p.Glu176del)	SERPINF2	Pathogenic	no assertion criteria provided
276	NM_000934.4(SERPINF2):c.1231G>A (p.Val411Met)	SERPINF2	Pathogenic	no assertion criteria provided
3160489	NM_000934.4(SERPINF2):c.472G>A (p.Gly158Ser)	SERPINF2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SERPINF2	Definitive	Autosomal recessive	alpha-2-plasmin inhibitor deficiency	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SERPINF2	Orphanet:79	Congenital alpha2-antiplasmin deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SERPINF2	HGNC:9075	ENSG00000167711	P08697	Alpha-2-antiplasmin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SERPINF2	Alpha-2-antiplasmin	Serine protease inhibitor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SERPINF2	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SERPINF2	129	broad	marker	right lobe of liver, liver, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SERPINF2	1,397

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SERPINF2	P08697	78.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Dissolution of Fibrin Clot	1	815.7×	0.006	SERPINF2
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.014	SERPINF2
Platelet activation, signaling and aggregation	1	105.7×	0.014	SERPINF2
Platelet degranulation	1	87.8×	0.014	SERPINF2
Hemostasis	1	36.0×	0.028	SERPINF2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of blood vessel diameter homeostasis by renin-angiotensin	1	5617.3×	0.002	SERPINF2
positive regulation of coagulation	1	2808.7×	0.002	SERPINF2
negative regulation of plasminogen activation	1	2407.4×	0.002	SERPINF2
positive regulation of transforming growth factor beta production	1	2106.5×	0.002	SERPINF2
negative regulation of fibrinolysis	1	1404.3×	0.002	SERPINF2
positive regulation of cell-cell adhesion mediated by cadherin	1	1296.3×	0.002	SERPINF2
fibrinolysis	1	842.6×	0.003	SERPINF2
blood vessel morphogenesis	1	802.5×	0.003	SERPINF2
positive regulation of collagen biosynthetic process	1	648.1×	0.003	SERPINF2
acute-phase response	1	421.3×	0.004	SERPINF2
positive regulation of smooth muscle cell proliferation	1	330.4×	0.005	SERPINF2
positive regulation of stress fiber assembly	1	312.1×	0.005	SERPINF2
positive regulation of cell differentiation	1	267.5×	0.005	SERPINF2
collagen fibril organization	1	224.7×	0.005	SERPINF2
positive regulation of JNK cascade	1	163.6×	0.007	SERPINF2
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.012	SERPINF2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	SERPINF2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SERPINF2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SERPINF2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SERPINF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.