SERPIND1

serpin family D member 1, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 22:20774112-20787720

Previous symbols: [ "HCF2" ]

Links

ENSG00000099937 ∙ NCBI:3053 ∙ OMIM:142360 ∙ HGNC:4838 ∙ Uniprot:P05546 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heparin cofactor 2 deficiency (Limited), mode of inheritance: Unknown
• heparin cofactor 2 deficiency (Definitive), mode of inheritance: AD
• heparin cofactor 2 deficiency (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Heparin cofactor II deficiency	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Hematologic	2863444; 3603411; 2647747; 1615493; 8902986; 8562924; 9607121; 10650845; 10494755; 12421148; 15337701
Individuals may be at higher risk for thrombophilia, though data are controversial, and may be clinically relevant only in the presence of another thrombophilia-related variant

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPIND1 gene.

• not provided (18 variants)
• Inborn genetic diseases (10 variants)
• Heparin cofactor II deficiency (5 variants)
• Deep venous thrombosis (1 variants)
• Thrombus (1 variants)
• Hemorrhage (1 variants)
• Thrombotic stroke (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPIND1 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				2	4	6
missense			20		3	23
nonsense		1	1			2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	1	22	2	7

Variants in SERPIND1

This is a list of pathogenic ClinVar variants found in the SERPIND1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-20779330-C-T			Likely benign (Mar 01, 2023)
22-20779352-A-G		not specified	Uncertain significance (Aug 02, 2021)
22-20779383-C-T		not specified	Likely benign (Aug 16, 2021)
22-20779430-C-T		SERPIND1-related disorder	Likely benign (May 10, 2019)
22-20779473-T-G		Heparin cofactor II deficiency	Uncertain significance (-)
22-20779527-A-AG		Heparin cofactor II deficiency	Uncertain significance (Mar 24, 2020)
22-20779530-G-A			Uncertain significance (Dec 31, 2022)
22-20779541-G-A		not specified	Uncertain significance (Oct 26, 2022)
22-20779543-C-A		Heparin cofactor II deficiency	Conflicting classifications of pathogenicity (Dec 01, 2023)
22-20779543-C-T			Benign (May 20, 2021)
22-20779572-G-A			Benign (Dec 01, 2022)
22-20779597-C-T		SERPIND1-related disorder	Benign (May 17, 2021)
22-20779598-G-A		SERPIND1-related disorder	Likely benign (Jul 12, 2019)
22-20779632-A-AT		Heparin cofactor II deficiency	Pathogenic (Feb 01, 1996)
22-20779732-G-C		SERPIND1-related disorder	Likely benign (Apr 29, 2020)
22-20779749-A-T			Likely benign (Mar 01, 2024)
22-20779777-C-T		SERPIND1-related disorder	Likely benign (Dec 30, 2020)
22-20779779-T-C			Benign (Jun 26, 2018)
22-20779800-G-C		Heparin cofactor II deficiency	Uncertain significance (-)
22-20779824-G-A		not specified	Uncertain significance (Aug 12, 2021)
22-20779844-C-T		not specified	Uncertain significance (Oct 18, 2021)
22-20779896-T-C		not specified	Uncertain significance (Feb 06, 2024)
22-20779934-C-T		not specified	Uncertain significance (Jan 31, 2023)
22-20779935-G-A		Heparin cofactor II deficiency	Benign (May 28, 2019)
22-20780012-C-T		Heparin cofactor II deficiency	Uncertain significance (Mar 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPIND1	protein_coding	protein_coding	ENST00000215727	4	13842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.51e-10	0.0786	125683	0	65	125748	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0568	288	285	1.01	0.0000173	3352
Missense in Polyphen		108	110.59	0.97659		1346
Synonymous	-0.899	127	115	1.11	0.00000773	953
Loss of Function	0.0923	15	15.4	0.975	8.20e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000789	0.000789
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000273	0.000273
Middle Eastern	0.000326	0.000326
South Asian	0.000229	0.000229
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner. {ECO:0000269|PubMed:1939083}.
• Disease: DISEASE: Thrombophilia due to heparin cofactor 2 deficiency (THPH10) [MIM:612356]: A hemostatic disorder characterized by a tendency to recurrent thrombosis. {ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:11204559, ECO:0000269|PubMed:15337701, ECO:0000269|PubMed:2647747}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Intrinsic Pathway of Fibrin Clot Formation;Hemostasis;Common Pathway of Fibrin Clot Formation;Formation of Fibrin Clot (Clotting Cascade) (Consensus)

Recessive Scores

• pRec: 0.267

Intolerance Scores

• loftool: 0.168
• rvis_EVS: 0.56
• rvis_percentile_EVS: 81.63

Haploinsufficiency Scores

• pHI: 0.724
• hipred: N
• hipred_score: 0.251
• ghis: 0.448

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Serpind1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; renal/urinary system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: chemotaxis;blood coagulation;negative regulation of endopeptidase activity;post-translational protein modification;cellular protein metabolic process
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;extracellular exosome
• Molecular function: endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity;heparin binding