SERPINF2

serpin family F member 2, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 17:1742835-1755265

Previous symbols: [ "PLI" ]

Links

ENSG00000167711 ∙ NCBI:5345 ∙ OMIM:613168 ∙ HGNC:9075 ∙ Uniprot:P08697 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• alpha-2-plasmin inhibitor deficiency (Supportive), mode of inheritance: AR
• alpha-2-plasmin inhibitor deficiency (Strong), mode of inheritance: AR
• alpha-2-plasmin inhibitor deficiency (Limited), mode of inheritance: AD
• alpha-2-plasmin inhibitor deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alpha-2-plasmin inhibitor deficiency	AD/AR	Hematologic	Anti-fibrinolytic agents or FFP can be used to treat bleeding episodes, and to and prevent patients hemorrhagic complications in those who are undergoing surgical interventions; Intramedullary hematoma is also a common feature, and awareness of this potential manifestation can be beneficial in order to institute efficient treatment; Heterozygotes may also have (milder) manifestations	Hematologic	82839; 156196; 89324; 7095605; 2496145; 2572590; 1806461; 9880645; 10583218; 11472338; 19141165; 19593116; 21873355

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINF2 gene.

• not provided (32 variants)
• Inborn genetic diseases (17 variants)
• not specified (5 variants)
• Abnormal bleeding (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINF2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	3	11
missense			17	5	4	26
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	4		5
non coding					6	6
Total	1	1	17	13	13

Highest pathogenic variant AF is 0.00000658

Variants in SERPINF2

This is a list of pathogenic ClinVar variants found in the SERPINF2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-1745000-C-T		not specified	Benign (Nov 12, 2018)
17-1745031-G-C		not specified	Uncertain significance (Jan 03, 2022)
17-1745172-C-T		Abnormal bleeding	Uncertain significance (Feb 01, 2019)
17-1745189-C-T			Likely benign (May 02, 2018)
17-1745208-C-T		not specified	Benign (-)
17-1745218-T-G			Likely benign (Dec 05, 2018)
17-1745328-C-T		SERPINF2-related disorder	Likely benign (Sep 19, 2019)
17-1745331-A-G			Likely pathogenic (Jul 05, 2022)
17-1745341-C-T			Benign (Dec 31, 2019)
17-1745346-C-T		not specified	Uncertain significance (Dec 03, 2021)
17-1745347-G-A			Likely benign (Jul 13, 2018)
17-1745702-C-T			Likely benign (Dec 31, 2019)
17-1745712-C-G		not specified	Uncertain significance (Jul 11, 2023)
17-1745728-C-T		not specified	Benign (-)
17-1745738-C-A		not specified	Uncertain significance (Aug 04, 2023)
17-1745766-C-A		not specified	Uncertain significance (Aug 15, 2023)
17-1745790-C-G		not specified	Uncertain significance (Jan 23, 2023)
17-1745793-G-A		not specified	Likely benign (May 04, 2022)
17-1745899-C-A			Uncertain significance (Jun 01, 2023)
17-1745903-G-A		not specified	Conflicting classifications of pathogenicity (Jul 29, 2023)
17-1745973-A-G			Benign (Nov 12, 2018)
17-1746874-C-T			Benign (Nov 12, 2018)
17-1747063-G-A		SERPINF2-related disorder	Benign (Dec 24, 2023)
17-1747123-G-A		not specified	Uncertain significance (Dec 18, 2023)
17-1747124-G-A		SERPINF2-related disorder	Likely benign (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINF2	protein_coding	protein_coding	ENST00000324015	9	12433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0136	0.985	125731	0	16	125747	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	229	288	0.796	0.0000181	3197
Missense in Polyphen		47	86.849	0.54117		1006
Synonymous	-0.130	135	133	1.01	0.00000943	1008
Loss of Function	2.83	7	21.0	0.334	0.00000100	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000190	0.000182
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000712	0.0000439
Middle Eastern	0.000218	0.000163
South Asian	0.0000654	0.0000653
Other	0.000654	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin. {ECO:0000269|PubMed:15853774}.
• Disease: DISEASE: Alpha-2-plasmin inhibitor deficiency (APLID) [MIM:262850]: An autosomal recessive disorder resulting in severe hemorrhagic diathesis. {ECO:0000269|PubMed:10583218, ECO:0000269|PubMed:2572590}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Blood Clotting Cascade;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Complement and Coagulation Cascades;Dissolution of Fibrin Clot;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.535

Intolerance Scores

• loftool: 0.0313
• rvis_EVS: -0.78
• rvis_percentile_EVS: 13.05

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.505
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.920

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Serpinf2
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of blood vessel diameter by renin-angiotensin;platelet degranulation;acute-phase response;response to organic substance;negative regulation of plasminogen activation;negative regulation of endopeptidase activity;collagen fibril organization;positive regulation of collagen biosynthetic process;fibrinolysis;positive regulation of cell differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of JNK cascade;blood vessel morphogenesis;positive regulation of smooth muscle cell proliferation;positive regulation of stress fiber assembly;negative regulation of fibrinolysis;positive regulation of ERK1 and ERK2 cascade;positive regulation of transforming growth factor beta production;positive regulation of cell-cell adhesion mediated by cadherin
• Cellular component: extracellular region;fibrinogen complex;extracellular space;cell surface;platelet alpha granule lumen;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: protease binding;endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity;protein binding;protein homodimerization activity