SERPINC1

serpin family C member 1

The protein encoded by this gene, antithrombin III, is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. Numerous mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency which constitutes a strong risk factor for thrombosis. A reduction in the serum level of this protein is associated with severe cases of Coronavirus Disease 19 (COVID-19).

provided by RefSeq


Biological Domains

Proteostasis, Structural Stabilization, Vasculature

Pharos Class

Tclin

Also known as

ENSG00000117601 (Ensembl Release 113)

UNIPROTKB P01008

ATIII, ATIII-R2, THPH7, AT3D, ATIII-T1, AT3, ATIII-T2

Summary of Evidence

This tab shows an overview of how the selected gene is associated with AD.

  • Genetic Association with LOAD

    Indicates whether or not this gene shows significant genetic association with Late Onset AD (LOAD) based on evidence from multiple studies compiled by the ADSP Gene Verification Committee
    False
  • Brain eQTL

    Indicates whether or not this gene locus has a significant expression Quantitative Trait Locus (eQTL) based on an AMP-AD consortium study
    False
  • RNA Expression Change in AD Brain

    Indicates whether or not this gene shows significant differential expression in at least one brain region based on AMP-AD consortium work. See ‘EVIDENCE’ tab.
    No data
  • Protein Expression Change in AD Brain

    Indicates whether or not this gene shows significant differential protein expression in at least one brain region based on AMP-AD consortium work. See ‘EVIDENCE’ tab.
    False
  • Nominated Target

    Indicates whether or not this gene has been submitted as a nominated target to Agora.
    False

AD Risk Scores

About AD Risk Scores

The TREAT-AD Center at Emory-Sage-SGC has developed a Target Risk Score (TRS) to objectively rank the potential involvement of specific genes in AD. The TRS is derived by summing two component risk scores, the Genetic Risk Score and the Multi-omic Risk Score, each of which is derived from a meta-analysis of multiple harmonized data sets. More information about the methodology used to define these risk scores is available here.

AD Risk Scores for SERPINC1

The TRS for SERPINC1, along with the component Genetic and Multi-omic Risk Scores, is shown here. The scores for SERPINC1 are superimposed on the genome-wide score distributions. If No Data is Currently Available is displayed for a score, that score was not calculated for SERPINC1.

Biological Domain Classification

About Biological Domains

A biological domain represents a standardized area of biology defined by a set of discrete, biologically coherent GO terms. The TREAT-AD Center at Emory-Sage-SGC has defined nineteen biological domains associated with AD, and objectively mapped genes to those biological domains using GO term annotations. More information about the methodology used to define AD biological domains, and to generate genome-wide biological domain mappings, is available here.

Biological Domains for SERPINC1

Select a biological domain on the left to see the list of GO terms that link SERPINC1 to it on the right. The percentage value displayed next to the currently selected biological domain indicates the proportion of SERPINC1's total unique GO terms that map to the biological domain. The ratio displayed on the right indicates how many of the biological domain's total GO terms SERPINC1 is annotated with.

BIOLOGICAL DOMAIN MAPPINGS

VasculatureProteostasisStructural StabilizationApoptosisAPP MetabolismAutophagyCell CycleDNA RepairEndolysosomeEpigeneticImmune ResponseLipid MetabolismMetal Binding and HomeostasisMitochondrial MetabolismMyelinationOxidative StressRNA SpliceosomeSynapseTau Homeostasis60.0%

LINKING GO TERMS FOR VASCULATURE (3/311)

  • Blood coagulation
  • Blood microparticle
  • Regulation of blood coagulation

RNA Expression

The results shown on this page are derived from a harmonized RNA-seq analysis of post-mortem brains from AD cases and controls. The samples were obtained from three human cohort studies across a total of nine different brain regions.


Overall Expression of SERPINC1 Across Brain Regions

This plot depicts the median expression of the selected gene across brain regions, as measured by RNA-seq read counts per million (CPM) reads. Meaningful expression is considered to be a log2 CPM greater than log2(5), depicted by the red line in the plot.

No data is currently available.

Filter the following charts by statistical model

Select a model

Differential Expression of SERPINC1 Across Brain Regions

After selecting a statistical model, you will be able to see whether the selected gene is differentially expressed between AD cases and controls. The box plot depicts how the differential expression of the selected gene of interest (purple dot) compares with expression of other genes in a given tissue. Summary statistics for each tissue can be viewed by hovering over the purple dots. Meaningful differential expression is considered to be a log2 fold change value greater than 0.263, or less than -0.263.

Brain region
No data is currently available.

Consistency of Change in Expression

This forest plot indicates the estimate of the log fold change with standard errors across the brain regions in the model chosen using the filter above. Genes that show consistent patterns of differential expression will have similar log-fold change value across brain regions.

LOG 2 FOLD CHANGE
No data is currently available.

Correlation of SERPINC1 with Hallmarks of AD

This plot depicts the association between expression levels of the selected gene in the DLPFC and three phenotypic measures of AD. An odds ratio > 1 indicates a positive correlation and an odds ratio < 1 indicates a negative correlation. Statistical significance and summary statistics for each phenotype can be viewed by hovering over the dots.

Phenotype
No data is currently available.

Similarly Expressed Genes

The network diagram below is based on a coexpression network analysis of RNA-seq data from AD cases and controls. The network analysis uses an ensemble methodology to identify genes that show similar coexpression across individuals.

The color of the edges and nodes indicates how frequently significant coexpression was identified. Each node represents a different gene and the amount of edges within the network. Darker edges represent coexpression in more brain regions.

No data is currently available.

Proteomics

Proteomic analyses of post-mortem brains show whether protein products of SERPINC1 are differentially expressed between AD cases and controls. Each box plot depicts how the differential expression of the protein(s) of interest (purple dot) compares with expression of other proteins in a given brain region. Summary statistics for each tissue can be viewed by hovering over the purple dots.


Targeted SRM Differential Protein Expression

Selected Reaction Monitoring (SRM) data was generated from the DLPFC region of post-mortem brains of over 1000 individuals from multiple human cohort studies.

Note that only a single SRM result is available for a given gene, as the probes used for this experiment were designed to match multiple protein products derived from each targeted gene.

Brain tissue
No data is currently available.

Genome-wide Differential Protein Expression

Select a protein from the dropdown menu to see whether it is differentially expressed between AD cases and controls.

P01008

The assay-specific box plots below depict how the differential expression of the selected protein of interest (purple dot) compares with expression of other proteins in each brain region that was assayed. Assay-specific summary statistics for each brain region can be viewed by hovering over the purple dot.

Multiple proteins may map to a single gene. Results from both TMT and LFQ assays are provided, however results for some proteins may be available for only one of the assays.


TMT Differential Protein Expression

Tandem mass tagged (TMT) data was generated from the DLPFC region of post-mortem brains of 400 individuals from the ROSMAP cohort.

Note that proteins may not be detected in this brain region; for these proteins, the plot will show no data.

Brain tissue
No data is currently available.

LFQ Differential Protein Expression

Liquid-free quantification (LFQ) data was generated from post-mortem brains of more than 500 individuals. Samples were taken from four human cohort studies, representing four different brain regions.

Note that proteins may not be detected in all four brain regions; for these proteins, the plot will show fewer than four brain regions.

Brain tissue
No data is currently available.

Metabolomics

The results shown on this page are derived from an analysis of metabolite levels from AD cases and controls. The samples were obtained from approximately 1400 individuals from the ADNI study. Metabolites are associated with genes using genetic mapping and the metabolite with the highest genetic association is shown for each gene.


Mapping of Metabolites to SERPINC1

No metabolomic data is currently available.


Levels of Metabolite by Disease Status

This plot shows differences in metabolite levels in AD cases and controls.

Diagnosis
No data is currently available.

Drug Development Resources

These external sites provide information and resources related to drug development.

Chemical Probes
View expert reviews and evaluations of any chemical probes that are available for this target.
Open Targets
View evidence on the validity of this therapeutic target based on genome-scale experiments and analysis.
PharmGKB
Search for information on gene-drug and gene-phenotype relationships.
Pharos
View information about this target in the Knowledge Management Center for the Illuminating the Druggable Genome program.
Probe Miner
Search for information on chemical probes based on large-scale, publicly available, medicinal chemistry data.
Protein Data Bank
Search for experimental and computed 3D protein structure information.

Additional Resources

These external sites provide additional information about therapeutic targets for AD and related dementias.

AD Atlas
Perform interactive network and enrichment analyses on this target using a heterogenous network of multiomic, association, and endophenotypic data.
Alzforum
Visit Alzforum for news and information resources about AD and related disorders.
AlzPED
Search for information on preclinical efficacy studies of candidate AD therapeutics.
AMP-PD Target Explorer
View evidence about whether this target is associated with Parkinson's Disease.
Brain Knowledge Platform
View single nucleus RNAseq results for this target using the Allen Institute SEA-AD Comparative Viewer.
Gene Ontology
View the GO terms associated with this target and explore ontology-related tools.
GeneCards
View integrated information about this target gathered from a comprehensive collection of public sources.
Genomics DB
View information about this target on the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) Genomics Database.
Pub AD
View dementia-related publication information for this target.
Reactome Pathways
View the reactome pathway information for this target on Ensembl.
SEA-AD
Explore the Seattle Alzheimer’s Disease Brain Cell Atlas resources from the Allen Institute.
UniProtKB
View protein sequence and functional information about this target.