The protein encoded by this intronless gene is an endothelial-specific type I membrane receptor that binds thrombin. This binding results in the activation of protein C, which degrades clotting factors Va and VIIIa and reduces the amount of thrombin generated. Mutations in this gene are a cause of thromboembolic disease, also known as inherited thrombophilia. [provided by RefSe... See more...

Aliases for THBD Gene

Aliases for THBD Gene

  • Thrombomodulin 2 3 4 5
  • CD141 Antigen 3 4
  • Fetomodulin 3 4
  • THRM 3 4
  • TM 3 4
  • THPH12 3
  • AHUS6 3
  • BDCA3 3
  • CD141 3

External Ids for THBD Gene

Previous GeneCards Identifiers for THBD Gene

  • GC20M023014
  • GC20M023021
  • GC20M022974

Summaries for THBD Gene

Entrez Gene Summary for THBD Gene

  • The protein encoded by this intronless gene is an endothelial-specific type I membrane receptor that binds thrombin. This binding results in the activation of protein C, which degrades clotting factors Va and VIIIa and reduces the amount of thrombin generated. Mutations in this gene are a cause of thromboembolic disease, also known as inherited thrombophilia. [provided by RefSeq, Jul 2008]

GeneCards Summary for THBD Gene

THBD (Thrombomodulin) is a Protein Coding gene. Diseases associated with THBD include Thrombophilia Due To Thrombomodulin Defect and Hemolytic Uremic Syndrome, Atypical 6. Among its related pathways are Cell surface interactions at the vascular wall and Formation of Fibrin Clot (Clotting Cascade). Gene Ontology (GO) annotations related to this gene include calcium ion binding and transmembrane signaling receptor activity.

UniProtKB/Swiss-Prot Summary for THBD Gene

  • Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.

Gene Wiki entry for THBD Gene

Additional gene information for THBD Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for THBD Gene

Genomics for THBD Gene

GeneHancer (GH) Regulatory Elements for THBD Gene

Promoters and enhancers for THBD Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around THBD on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for THBD

Top Transcription factor binding sites by QIAGEN in the THBD gene promoter:
  • AREB6
  • ARP-1
  • ATF
  • Brachyury
  • LCR-F1
  • NF-kappaB
  • NF-kappaB1
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)

Genomic Locations for THBD Gene

Genomic Locations for THBD Gene
chr20:23,045,633-23,049,741
(GRCh38/hg38)
Size:
4,109 bases
Orientation:
Minus strand
chr20:23,026,270-23,030,378
(GRCh37/hg19)
Size:
4,109 bases
Orientation:
Minus strand

Genomic View for THBD Gene

Genes around THBD on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
THBD Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for THBD Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for THBD Gene

Proteins for THBD Gene

  • Protein details for THBD Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P07204-TRBM_HUMAN
    Recommended name:
    Thrombomodulin
    Protein Accession:
    P07204
    Secondary Accessions:
    • Q8IV29
    • Q9UC32

    Protein attributes for THBD Gene

    Size:
    575 amino acids
    Molecular mass:
    60329 Da
    Quaternary structure:
    • Interacts with ITGAL, ITGAM and ITGB2.

    Three dimensional structures from OCA and Proteopedia for THBD Gene

neXtProt entry for THBD Gene

Post-translational modifications for THBD Gene

  • N-glycosylated.
  • The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
  • Glycosylation at Asn47, Asn115, Asn116, Asn382, Asn409, Ser490, and Ser492
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • TRBM_HUMAN (591)

Other Protein References for THBD Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for THBD Gene

Domains & Families for THBD Gene

Gene Families for THBD Gene

HGNC:
Human Protein Atlas (HPA):
  • Candidate cardiovascular disease genes
  • CD markers
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for THBD Gene

Blocks:
  • Aspartic acid and asparagine hydroxylation site
  • EGF-like calcium-binding
  • Thrombomodulin signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for THBD Gene

GenScript: Design optimal peptide antigens:
  • Fetomodulin (TRBM_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P07204

UniProtKB/Swiss-Prot:

TRBM_HUMAN :
  • Extracellular region (481-515) contains a binding side for alpha-L/beta-2 and alpha-M/beta-2 integrin.
Domain:
  • Extracellular region (481-515) contains a binding side for alpha-L/beta-2 and alpha-M/beta-2 integrin.
genes like me logo Genes that share domains with THBD: view

Function for THBD Gene

Molecular function for THBD Gene

UniProtKB/Swiss-Prot Function:
Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.
GENATLAS Biochemistry:
thrombomodulin coagulation factor complexing with thrombin,the complex activating PROC,with mutations in the promoter region putatively associated with a risk for arterial thrombosis and myocardial infarction

Phenotypes From GWAS Catalog for THBD Gene

Gene Ontology (GO) - Molecular Function for THBD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004888 transmembrane signaling receptor activity IEA --
GO:0005509 calcium ion binding TAS,IEA --
GO:0005515 protein binding IPI 14691232
GO:0038023 signaling receptor activity TAS 2822087
genes like me logo Genes that share ontologies with THBD: view
genes like me logo Genes that share phenotypes with THBD: view

Human Phenotype Ontology for THBD Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for THBD Gene

MGI Knock Outs for THBD:
  • Thbd Thbd<tm2Rdr>
  • Thbd Thbd<tm1Rdr>
  • Thbd Thbd<tm2.1Emc>
  • Thbd Thbd<tm1.1(KOMP)Vlcg>
  • Thbd Thbd<tm2Emc>

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for THBD Gene

Localization for THBD Gene

Subcellular locations from UniProtKB/Swiss-Prot for THBD Gene

Membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for THBD gene
Compartment Confidence
plasma membrane 5
extracellular 4
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
endosome 2
cytosol 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for THBD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IEA --
GO:0005774 vacuolar membrane IEA --
GO:0005886 plasma membrane IEA,TAS --
GO:0005887 integral component of plasma membrane TAS,IEA --
GO:0009986 cell surface IDA 17379830
genes like me logo Genes that share ontologies with THBD: view

Pathways & Interactions for THBD Gene

genes like me logo Genes that share pathways with THBD: view

Pathways by source for THBD Gene

SIGNOR curated interactions for THBD Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for THBD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007565 female pregnancy IEA --
GO:0007596 blood coagulation TAS --
GO:0007599 hemostasis IEA --
GO:0010165 response to X-ray IEA --
GO:0010544 negative regulation of platelet activation TAS 17379830
genes like me logo Genes that share ontologies with THBD: view

Drugs & Compounds for THBD Gene

(77) Drugs for THBD Gene - From: DrugBank, PharmGKB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Warfarin Approved Pharma 593
Dexibuprofen Approved, Investigational Pharma Target, modulator 0
Drotrecogin alfa Approved, Investigational, Withdrawn Pharma Target 0
Ibuprofen Approved Pharma Channel blocker, Inhibition, Inhibitor, Target, inducer 677

(61) Additional Compounds for THBD Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with THBD: view

Transcripts for THBD Gene

mRNA/cDNA for THBD Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for THBD Gene

No ASD Table

Relevant External Links for THBD Gene

GeneLoc Exon Structure for
THBD

Expression for THBD Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for THBD Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for THBD Gene

This gene is overexpressed in Pancreas (55.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for THBD Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for THBD

SOURCE GeneReport for Unigene cluster for THBD Gene:

Hs.2030

mRNA Expression by UniProt/SwissProt for THBD Gene:

P07204-TRBM_HUMAN
Tissue specificity: Endothelial cells are unique in synthesizing thrombomodulin.

Evidence on tissue expression from TISSUES for THBD Gene

  • Lung(4.7)
  • Nervous system(4.5)
  • Heart(3.5)
  • Blood(3.2)
  • Spleen(3.2)
  • Lymph node(2.6)
  • Muscle(2.5)
  • Skin(2.5)
  • Kidney(2.3)
  • Liver(2.1)
  • Pancreas(2.1)
  • Bone marrow(2)
  • Intestine(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for THBD Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • head
Thorax:
  • heart
  • lung
Abdomen:
  • kidney
  • liver
  • pancreas
General:
  • blood
  • blood vessel
  • coagulation system
  • red blood cell
  • skin
genes like me logo Genes that share expression patterns with THBD: view

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for THBD Gene

Orthologs for THBD Gene

This gene was present in the common ancestor of chordates.

Orthologs for THBD Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia THBD 31 30
  • 99.25 (n)
OneToOne
dog
(Canis familiaris)
Mammalia THBD 31 30
  • 80.45 (n)
OneToOne
cow
(Bos Taurus)
Mammalia THBD 31 30
  • 77.93 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Thbd 17 31 30
  • 73.53 (n)
rat
(Rattus norvegicus)
Mammalia Thbd 30
  • 71.95 (n)
oppossum
(Monodelphis domestica)
Mammalia THBD 31
  • 46 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia THBD 31
  • 40 (a)
OneToOne
chicken
(Gallus gallus)
Aves THBD 31 30
  • 58.88 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia thbd 30
  • 49.37 (n)
zebrafish
(Danio rerio)
Actinopterygii THBD 31
  • 27 (a)
OneToOne
Species where no ortholog for THBD was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for THBD Gene

ENSEMBL:
Gene Tree for THBD (if available)
TreeFam:
Gene Tree for THBD (if available)
Aminode:
Evolutionary constrained regions (ECRs) for THBD: view image

Paralogs for THBD Gene

No data available for Paralogs for THBD Gene

Variants for THBD Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for THBD Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
626991 Uncertain Significance: Abnormal bleeding 23,048,148(-) C/T MISSENSE_VARIANT
627170 Likely Pathogenic: Abnormal bleeding 23,048,017(-) CG/C FRAMESHIFT_VARIANT
627236 Uncertain Significance: Abnormal bleeding 23,048,072(-) G/A MISSENSE_VARIANT
627252 Likely Pathogenic: Abnormal bleeding 23,047,894(-) G/T NONSENSE
627282 Likely Pathogenic: Abnormal thrombosis 23,049,259(-) GC/G FRAMESHIFT_VARIANT

Additional dbSNP identifiers (rs#s) for THBD Gene

Structural Variations from Database of Genomic Variants (DGV) for THBD Gene

Variant ID Type Subtype PubMed ID
esv2758789 CNV loss 17122850
nsv482065 CNV gain 20164927

Variation tolerance for THBD Gene

Residual Variation Intolerance Score: 78.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.10; 69.11% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for THBD Gene

Human Gene Mutation Database (HGMD)
THBD
SNPedia medical, phenotypic, and genealogical associations of SNPs for
THBD

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for THBD Gene

Disorders for THBD Gene

MalaCards: The human disease database

(109) MalaCards diseases for THBD Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
thrombophilia due to thrombomodulin defect
  • thph12
hemolytic uremic syndrome, atypical 6
  • hemolytic uremic syndrome, atypical, susceptibility to, 6
atypical hemolytic uremic syndrome with complement gene abnormality
  • ahus with complement gene abnormality
thrombosis
  • thrombosis of blood vessel
thrombophilia
  • hypercoagulability state
- elite association - COSMIC cancer census association via MalaCards
Search THBD in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TRBM_HUMAN
  • Thrombophilia due to thrombomodulin defect (THPH12) [MIM:614486]: A hemostatic disorder characterized by a tendency to thrombosis. {ECO:0000269 PubMed:12139752, ECO:0000269 PubMed:7811989, ECO:0000269 PubMed:9198186}. Note=The disease may be caused by mutations affecting the gene represented in this entry. The role of thrombomodulin in thrombosis is controversial. It is likely that genetic or environmental risk factors in addition to THBD variation are involved in the pathogenesis of venous thrombosis.
  • Hemolytic uremic syndrome atypical 6 (AHUS6) [MIM:612926]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269 PubMed:19625716, ECO:0000269 PubMed:20513133}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.

Genatlas disease for THBD Gene

thrombosis,recurrent

Additional Disease Information for THBD

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with THBD: view

Publications for THBD Gene

  1. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. (PMID: 19625716) Delvaeye M … Conway EM (The New England journal of medicine 2009) 3 4 23 41 54
  2. Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease. (PMID: 11245641) Wu KK … Atherosclerosis Risk in Communities Study (ARIC) Investigators (Circulation 2001) 3 4 23 41 54
  3. Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. (PMID: 20513133) Maga TK … Smith RJ (Human mutation 2010) 3 4 41 54
  4. Thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population-based case-control study. (PMID: 15842356) Heit JA … Melton LJ (Journal of thrombosis and haemostasis : JTH 2005) 3 23 41 54
  5. Genetic risk for restenosis after coronary balloon angioplasty. (PMID: 15135268) Horibe H … Yokota M (Atherosclerosis 2004) 3 23 41 54

Products for THBD Gene

  • Signalway ELISA kits for THBD
  • Signalway Proteins for THBD

Sources for THBD Gene