SERPINC1

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

Basic information

Region (hg38): 1:173903800-173917327

Previous symbols: [ "AT3" ]

Links

ENSG00000117601 ∙ NCBI:462 ∙ OMIM:107300 ∙ HGNC:775 ∙ Uniprot:P01008 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary antithrombin deficiency (Strong), mode of inheritance: AD
• hereditary antithrombin deficiency (Strong), mode of inheritance: AR
• hereditary antithrombin deficiency (Definitive), mode of inheritance: AR
• hereditary antithrombin deficiency (Supportive), mode of inheritance: AD
• hereditary antithrombin deficiency (Strong), mode of inheritance: AD
• hereditary antithrombin deficiency (Strong), mode of inheritance: AR
• hereditary antithrombin deficiency (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Antithrombin III deficiency	AD/AR	Hematologic	Individuals may be at high risk for thromboembolism, and recognition may allow preventive/prophylactic measures as well as prompt treatment of thromboembolic and related manifestations, including medical treatment with antithrombin, and chronic anticoagulations, which is indicated in asymptomatic individuals as well as those who have previously suffered sequelae	Hematologic	14347873; 6582486; 3055413; 3350974; 1868237; 2146503; 1671110; 8091378; 16705712; 18208532; 19760264; 21655678; 21655682; 21240680; 21325262; 22997155; 22961244
The inheritance depends on specific variant

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINC1 gene.

• Hereditary antithrombin deficiency (44 variants)
• not provided (6 variants)
• Deep venous thrombosis (2 variants)
• SERPINC1-related disorder (2 variants)
• Tuberous sclerosis 2 (1 variants)
• Abnormal thrombosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINC1 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	54	4	60
missense	20	29	82	5	2	138
nonsense	12	4				16
start loss						0
frameshift	10	9				19
inframe indel	2	1	2			5
splice donor/acceptor (+/-2bp)	4	4				8
splice region		2	5	7		14
non coding	1		1	11	9	22
Total	49	47	87	70	15

Highest pathogenic variant AF is 0.000840

Variants in SERPINC1

This is a list of pathogenic ClinVar variants found in the SERPINC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-173903889-T-G		Hereditary antithrombin deficiency	Uncertain significance (Feb 04, 2022)
1-173903891-A-G		Hereditary antithrombin deficiency	Likely pathogenic (Feb 01, 2019)
1-173903896-A-G		See cases	Uncertain significance (Dec 08, 2021)
1-173903902-G-A		Hereditary antithrombin deficiency	Pathogenic (Sep 06, 2017)
1-173903902-GGGTTGGCTA-G		Hereditary antithrombin deficiency	Pathogenic (Dec 01, 1994)
1-173903908-G-T		Hereditary antithrombin deficiency	Likely pathogenic (Feb 01, 2019)
1-173903918-C-G		Hereditary antithrombin deficiency	Pathogenic (Aug 02, 2023)
1-173903926-A-G		Hereditary antithrombin deficiency	Pathogenic (Oct 30, 2023)
1-173903926-A-TTAT		SERPINC1-related disorder	Uncertain significance (Jul 21, 2023)
1-173903929-A-G		Hereditary antithrombin deficiency	Uncertain significance (Sep 06, 2022)
1-173903934-G-A		Hereditary antithrombin deficiency	Likely benign (Jan 25, 2024)
1-173903942-G-A		Hereditary antithrombin deficiency	Uncertain significance (Apr 28, 2017)
1-173903946-T-C		Hereditary antithrombin deficiency	Likely benign (Oct 30, 2023)
1-173903953-A-T		Hereditary antithrombin deficiency	Uncertain significance (Nov 13, 2020)
1-173903968-G-A		Hereditary antithrombin deficiency	Likely pathogenic (Jan 25, 2024)
1-173903969-G-A		Hereditary antithrombin deficiency • Deep venous thrombosis	Uncertain significance (Feb 19, 2024)
1-173903969-G-C		Hereditary antithrombin deficiency	Likely pathogenic (Aug 21, 2019)
1-173903969-G-T		Abnormal thrombosis • Hereditary antithrombin deficiency	Pathogenic (Sep 21, 2023)
1-173903971-C-A		Hereditary antithrombin deficiency	Uncertain significance (Feb 19, 2024)
1-173903972-T-C		Hereditary antithrombin deficiency	Uncertain significance (Feb 19, 2024)
1-173903973-G-C		Hereditary antithrombin deficiency	Pathogenic (Feb 19, 2024)
1-173903978-C-T		Hereditary antithrombin deficiency	Likely pathogenic (Aug 16, 2024)
1-173903982-G-T		Hereditary antithrombin deficiency	Likely pathogenic (Jan 11, 2022)
1-173903983-A-C		Hereditary antithrombin deficiency	Uncertain significance (Feb 19, 2024)
1-173903986-G-T		SERPINC1-related disorder	Uncertain significance (Sep 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINC1	protein_coding	protein_coding	ENST00000367698	7	13570

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00108	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.36	199	261	0.763	0.0000152	3061
Missense in Polyphen		71	98.983	0.71729		1278
Synonymous	0.0480	101	102	0.994	0.00000596	906
Loss of Function	4.12	0	19.8	0.00	0.00000120	235

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin. {ECO:0000269|PubMed:15853774}.
• Disease: DISEASE: Antithrombin III deficiency (AT3D) [MIM:613118]: An important risk factor for hereditary thrombophilia, a hemostatic disorder characterized by a tendency to recurrent thrombosis. Antithrombin-III deficiency is classified into 4 types. Type I: characterized by a 50% decrease in antigenic and functional levels. Type II: has defects affecting the thrombin-binding domain. Type III: alteration of the heparin-binding domain. Plasma AT-III antigen levels are normal in type II and III. Type IV: consists of miscellaneous group of unclassifiable mutations. {ECO:0000269|PubMed:10997988, ECO:0000269|PubMed:11713457, ECO:0000269|PubMed:11794707, ECO:0000269|PubMed:12353073, ECO:0000269|PubMed:12595305, ECO:0000269|PubMed:12894857, ECO:0000269|PubMed:15164384, ECO:0000269|PubMed:1547341, ECO:0000269|PubMed:1555650, ECO:0000269|PubMed:16908819, ECO:0000269|PubMed:1906811, ECO:0000269|PubMed:2013320, ECO:0000269|PubMed:2229057, ECO:0000269|PubMed:2365065, ECO:0000269|PubMed:23910795, ECO:0000269|PubMed:2781509, ECO:0000269|PubMed:3080419, ECO:0000269|PubMed:3162733, ECO:0000269|PubMed:3179438, ECO:0000269|PubMed:3191114, ECO:0000269|PubMed:3805013, ECO:0000269|PubMed:6582486, ECO:0000269|PubMed:7734359, ECO:0000269|PubMed:7832187, ECO:0000269|PubMed:7878627, ECO:0000269|PubMed:7959685, ECO:0000269|PubMed:7981186, ECO:0000269|PubMed:7989582, ECO:0000269|PubMed:7994035, ECO:0000269|PubMed:8274732, ECO:0000269|PubMed:8443391, ECO:0000269|PubMed:8486379, ECO:0000269|PubMed:9031473, ECO:0000269|PubMed:9157604, ECO:0000269|PubMed:9759613, ECO:0000269|PubMed:9845533, ECO:0000269|Ref.3, ECO:0000269|Ref.55}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Ardeparin Action Pathway;Heparin Action Pathway;Fondaparinux Action Pathway;Enoxaparin Action Pathway;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);Glypican 1 network (Consensus)

Recessive Scores

• pRec: 0.565

Intolerance Scores

• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.22

Haploinsufficiency Scores

• pHI: 0.452
• hipred: Y
• hipred_score: 0.801
• ghis: 0.671

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.143

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Serpinc1
• Phenotype: pigmentation 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); reproductive system phenotype; 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); liver/biliary system phenotype; embryo phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: serpinc1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased life span

Gene ontology

• Biological process: acute inflammatory response to antigenic stimulus;response to nutrient;lactation;blood coagulation;negative regulation of endopeptidase activity;post-translational protein modification;cellular protein metabolic process;regulation of blood coagulation, intrinsic pathway
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;plasma membrane;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: protease binding;serine-type endopeptidase inhibitor activity;protein binding;heparin binding;identical protein binding