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Set Analyses:

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THBD Gene

protein-coding GIFtS: 66
GCID: GC20M023026

Thrombomodulin

Microbiology & Infectious Diseases Congress

See related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
thrombomodulin¹ ²		THPH12² ⁵
THRM² ³ ⁵		BDCA3²
TM² ³		CD141²
CD141 Antigen² ³		fetomodulin²
AHUS6² ⁵		Fetomodulin³

External Ids:	HGNC: 11784¹	Entrez Gene: 7056²	Ensembl: ENSG00000178726⁷	OMIM: 188040⁵	UniProtKB: P07204³

Export aliases for THBD gene to outside databases

Previous GC identifers: GC20M023014 GC20M023021 GC20M022974

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 thbd-related atypical hemolytic-uremic syndrome. GO annotations related to this gene include carbohydrate binding and calcium ion binding. An important paralog of this gene is CLEC14A.

UniProtKB/Swiss-Prot: TRBM_HUMAN, P07204

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

Gene Wiki entry for THBD (Thrombomodulin) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000020.11 NC_018931.2 NT_011387.9

Regulatory elements:

Regulatory transcription factor binding sites in the THBD gene promoter:
Brachyury POU3F2 (N-Oct-5a) POU3F2 (N-Oct-5b) LCR-F1 POU3F2 NF-kappaB AREB6 ARP-1 NF-kappaB1 ATF
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: THBD promoter sequence

Search Chromatin IP Primers for THBD

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat THBD

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20p11.2 Ensembl cytogenetic band: 20p11.21 HGNC cytogenetic band: 20p11.21

THBD Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
THBD gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20M023026: view genomic region (about GC identifiers)

Start:	23,026,270 bp from pter	End:	23,030,378 bp from pter
Size:	4,109 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: TRBM_HUMAN, P07204 (See protein sequence)

Recommended Name: Thrombomodulin precursor

Size: 575 amino acids; 60329 Da

Selected PDB 3D structures from and Proteopedia for THBD (see all 11):

1ADX (3D)

1DQB (3D)

1DX5 (3D)

1EGT (3D)

1FGD (3D)

1FGE (3D)

Secondary accessions: Q8IV29 Q9UC32

Explore the universe of human proteins at neXtProt for THBD: NX_P07204

Explore proteomics data for THBD at MOPED

Post-translational modifications:

N-glycosylated¹

The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF

domains¹

Glycosylation² at Asn47, Asn115, Asn116, Asn382, Asn409, Ser490, Ser492

Modification sites at PhosphoSitePlus

See THBD Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_000352.1

ENSEMBL proteins:

ENSP00000366307

Reactome Protein details: P07204

THBD Human Recombinant Protein Products:

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	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells Browse OriGene Protein Over-expression Lysates OriGene Custom MassSpec OriGene Custom Protein Services for THBD
	GenScript Custom Purified and Recombinant Proteins Services for THBD
	Novus Biologicals THBD Protein
	Sino Biological Recombinant Protein for THBD Sino Biological Cell Lysate for THBD
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Cloud-Clone Corp.

THBD Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of THBD
	R&D Systems Antibodies for THBD (Thrombomodulin/BDCA-3)
	OriGene Antibodies for THBD OriGene Custom Antibody Services for THBD
	Novus Biologicals THBD Antibodies
	Abcam antibodies for THBD
	Browse Antibodies at Cloud-Clone Corp.
	ThermoFisher Antibody for THBD
	LSBio Antibodies in human, mouse, rat for THBD

THBD Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for THBD
	R&D Systems ELISAs for THBD (Thrombomodulin/BDCA-3)
	GenScript Custom Assay Services for THBD
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

CD: CD molecules

Selected InterPro protein domains (see all 12):

IPR015149 Tme5_EGF-like

IPR001491 Thrombomodulin

IPR016187 C-type_lectin_fold

IPR001881 EGF-like_Ca-bd_dom

IPR000742 EG-like_dom

Graphical View of Domain Structure for InterPro Entry P07204

ProtoNet protein and cluster: P07204

3 Blocks protein domains:

IPB000152 Aspartic acid and asparagine hydroxylation site

IPB001491 Thrombomodulin signature

IPB001881 EGF-like calcium-binding

UniProtKB/Swiss-Prot: TRBM_HUMAN, P07204

Similarity: Contains 1 C-type lectin domain

Similarity: Contains 6 EGF-like domains

THBD for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: TRBM_HUMAN, P07204

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 entry for THBD:

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

Gene Ontology (GO): 5 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004872	receptor activity	TAS	2822087
GO:0004888	transmembrane signaling receptor activity	IEA	--
GO:0005509	calcium ion binding	IEA	--
GO:0005515	protein binding	IPI	14691232
GO:0030246	carbohydrate binding	IEA	--

THBD for ontologies About GeneDecksing

Phenotypes:
1 GenomeRNAi human phenotype for THBD:

Increased cell number in G1, s

Selected MGI mutant phenotypes (inferred from 10 alleles) (MGI details for Thbd) (see all 16):

cardiovascular system	cellular	digestive/alimentary	embryogenesis	growth/size/body
hematopoietic system	homeostasis/metabolism	immune system	integument	liver/biliary system
mortality/aging	nervous system	normal	renal/urinary system	reproductive system

THBD for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-outs for THBD: Thbd^tm1Rdr Thbd^tm2.1Emc Thbd^tm2Emc

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for THBD

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for THBD

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for THBD

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for THBD

miRNA Products:		miRTarBase miRNAs that target THBD: hsa-mir-215-5p (MIRT024294), hsa-mir-192-5p (MIRT026159), hsa-mir-335-5p (MIRT017044)

		Block miRNA regulation of human, mouse, rat THBD using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate THBD (see all 24):
		hsa-miR-124* hsa-miR-520d-5p hsa-miR-4328 hsa-miR-323b-3p hsa-miR-578 hsa-miR-520a-5p hsa-miR-3916 hsa-miR-3125

		SwitchGear 3'UTR luciferase reporter plasmid: THBD 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for THBD
		Predesigned siRNA for gene silencing in human, mouse, rat THBD

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for THBD

Clone Products:		OriGene clones in human, mouse for THBD (see all 6) OriGene ORF clones in mouse, rat for THBD OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: THBD (NM_000361)
		Sino Biological Human cDNA Clone for THBD
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for THBD
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat THBD

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for THBD
		Browse ESI BIO Cell Lines and PureStem Progenitors for THBD

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for THBD

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

TRBM_HUMAN, P07204: Membrane; Single-pass type I membrane protein

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
plasma membrane	4
extracellular	3
cytoskeleton	2
cytosol	2
nucleus	2

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Gene Ontology (GO): 5 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005615	extracellular space	IEA	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral component of plasma membrane	TAS	2822087
GO:0009986	cell surface	IDA	17379830
GO:0016021	integral component of membrane	--	--

THBD for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for THBD About (see all 7)

See pathways by source

SuperPath

Contained pathways About

Formation of Fibrin Clot (Clotting Cascade)

	Formation of Fibrin Clot (Clotting Cascade)	0.51			Common Pathway	0.00
	Blood Coagulation Signaling Pathways	0.51			Extrinsic Prothrombin Activation Pathway	0.00

Complement and coagulation cascades

Complement and coagulation cascades

0.71

Complement and Coagulation Cascades

0.71

Collagen biosynthesis and modifying enzymes

Intrinsic Prothrombin Activation Pathway

0.39

Blood Coagulation Cascade

0.38

Hemostasis

Hemostasis

0.43

Validated transcriptional targets of AP1 family members Fra1 and Fra2

Validated transcriptional targets of AP1 family members Fra1 and Fra2

Pathways by source See SuperPaths
Show all pathways

1 R&D Systems Pathway for THBD

Blood Coagulation Signaling Pathways

3 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for THBD

	Extrinsic Prothrombin Activation Pathway
	Blood Coagulation Cascade
	Intrinsic Prothrombin Activation Pathway

2 BioSystems Pathways for THBD

	Complement and Coagulation Cascades
	Validated transcriptional targets of AP1 family members Fra1 and Fra2

2 Reactome Pathways for THBD

	Cell surface interactions at the vascular wall
	Common Pathway

1 Kegg Pathway (Kegg details for THBD):

Complement and coagulation cascades

THBD for pathways About GeneDecksing

Pathway & Disease-focused RT² Profiler PCR Arrays including THBD:

Endothelial Cell Biology in human mouse rat

Polycomb & Trithorax Target Genes in human mouse rat

Interactions:

GeneGlobe Interaction Network for THBD

STRING Interaction Network Preview (showing 5 interactants - click image to see 9)

Selected Interacting proteins for THBD (P07204^{1, 3} ENSP00000366307⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 9)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
F2	P00734¹^,³, ENSP00000308541⁴	EBI-941422,EBI-297094 I2D: score=4 STRING: ENSP00000308541
PF4	P02776³, ENSP00000296029⁴	I2D: score=3 STRING: ENSP00000296029
PROC	P04070³, ENSP00000234071⁴	I2D: score=1 STRING: ENSP00000234071
SERPINA5	P05154³, ENSP00000333203⁴	I2D: score=1 STRING: ENSP00000333203
F10	ENSP00000364709⁴	STRING: ENSP00000364709

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Gene Ontology (GO): Selected biological process terms (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0007565	female pregnancy	IEA	--
GO:0007596	blood coagulation	TAS	--
GO:0009790	embryo development	IEA	--
GO:0010165	response to X-ray	IEA	--
GO:0010544	negative regulation of platelet activation	TAS	17379830

THBD for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for THBD (TRBM)

2 DrugBank Compounds for THBD About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Drotrecogin alfa	Anticoagulant protein C (see all 4)	60202-16-6	target	--	1660324 2836377 15252033 11804648 3039877
Ibuprofen	Ibuprophen (see all 3)	15687-27-1	target	modulator	22668799

Selected Novoseek inferred chemical compound relationships for THBD gene (see all 135) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
fibrinogen	79.5	200	1650482 (3), 1651430 (3), 7660145 (2), 15198737 (2) (see all 99)
hirudin	71.6	40	2176873 (4), 1658403 (3), 7646471 (2), 11755958 (2) (see all 25)
hirugen	64.3	9	1317850 (4), 19638274 (1), 9035728 (1)
heparin	64.2	101	16376423 (8), 17597201 (4), 1658403 (3), 10545182 (2) (see all 53)
ch 55	61.3	2	9269772 (1), 9720716 (1)
b 723	61	16	16056246 (3), 12883236 (2), 10672054 (1), 14652817 (1) (see all 13)
gamma-carboxyglutamic acid	60.4	10	9395524 (4), 1964460 (1), 19129181 (1)
ximelagatran	59.3	3	14648923 (1), 16353054 (1), 14727932 (1)
prostacyclin	59.2	50	1706920 (3), 8134903 (2), 11094038 (2), 9735245 (1) (see all 29)
chondroitin sulfate	56.8	101	8381406 (9), 7929188 (5), 8163479 (4), 17549291 (3) (see all 26)

THBD for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for THBD gene:

NM_000361.2

Unigene Cluster for THBD:

Thrombomodulin

Hs.2030 [show with all ESTs]

Unigene Representative Sequence: NM_000361

1 Ensembl transcript including schematic representation, and UCSC links where relevant:

ENST00000377103(uc002wss.3)

Congresses - knowledge worth sharing:
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

miRNA Products:		Block miRNA regulation of human, mouse, rat THBD using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate THBD (see all 24):
		hsa-miR-124* hsa-miR-520d-5p hsa-miR-4328 hsa-miR-323b-3p hsa-miR-578 hsa-miR-520a-5p hsa-miR-3916 hsa-miR-3125

		SwitchGear 3'UTR luciferase reporter plasmid: THBD 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for THBD
		Predesigned siRNA for gene silencing in human, mouse, rat THBD

Clone Products:		OriGene clones in human, mouse for THBD (see all 6) OriGene ORF clones in mouse, rat for THBD OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: THBD (NM_000361)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for THBD
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat THBD

Primer Products:		OriGene qPCR primer pairs and template standards for THBD OriGene qSTAR qPCR primer pairs in human, mouse for THBD
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat THBD
		QuantiTect SYBR Green Assays in human, mouse, rat THBD
		QuantiFast Probe-based Assays in human, mouse, rat THBD

Additional mRNA sequence:

AK091934.1 AK123557.1 BC035602.1 BC053357.1 CR749513.1 M16552.1 X05495.1

5 DOTS entries:

DT.416446 DT.92427537 DT.100755305 DT.100755302 DT.95196185

Selected AceView cDNA sequences (see all 122):

NM_000361 BQ614514 BQ921087 BX112338 CA306101 BC035602 M16552 BC053357

BI711304 AA962556 BI711717 CR749513 T80997 CK905980 BQ268099 AI215479

AA256849 N20638 BQ267846 R22425 BQ004656 BF477361 BI962928 BP355507

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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THBD expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: AAATATAGAT

About this image

THBD expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 19) fully expand


Cartilage (Muscoskeletal System) fully expand to see all 4 entries
Intervertebral Disc Nucleus Pulposus Cells Nucleus Pulposus
Nucleus Pulposus

Hypoblast (Extraembryonic Tissues)
Extraembryonic Endoderm Cells Extraembryonic Endoderm

Yolk Sac (Extraembryonic Tissues)
Extraembryonic Endoderm Cells Extraembryonic Endoderm

Bone (Muscoskeletal System) fully expand to see all 2 entries
Mesenchymal Condensate Cells Zeugopod
Stylopod Long Bone

Lung (Respiratory System) fully expand to see all 2 entries
Basal Cells Respiratory Bronchioles
Trachea

THBD Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

THBD Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.2030

UniProtKB/Swiss-Prot: TRBM_HUMAN, P07204

Tissue specificity: Endothelial cells are unique in synthesizing thrombomodulin

Pathway & Disease-focused RT² Profiler PCR Arrays including THBD:

Endothelial Cell Biology in human mouse rat

Polycomb & Trithorax Target Genes in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for THBD OriGene qSTAR qPCR primer pairs in human, mouse for THBD
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat THBD
		QuantiTect SYBR Green Assays in human, mouse, rat THBD
		QuantiFast Probe-based Assays in human, mouse, rat THBD

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for THBD

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for THBD gene from Selected species (see all 10) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Thbd^{1 , 5}	thrombomodulin^{1, 5}	73.53(n)¹ 68.59(a)¹		2 (73.45 cM)⁵ 21824¹ NM_009378.3¹ NP_033404.1¹ 148404466⁵
chicken (Gallus gallus)	Aves	THBD¹	thrombomodulin	58.88(n) 46.5(a)		101752029 XM_004940137.1 XP_004940194.1
tropical clawed frog (Xenopus tropicalis)	Amphibia	thbd¹	thrombomodulin	49.37(n) 40.88(a)		100485229 XM_002936923.2 XP_002936969.1
zebrafish (Danio rerio)	Actinopterygii	THBD⁶	thrombomodulin	27(a)	1 ↔ 1	20(51802111-51803520) ENSDARG00000092470

ENSEMBL Gene Tree for THBD (if available)
TreeFam Gene Tree for THBD (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for THBD gene

CLEC14A² CD93² CD248²

THBD for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 20 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs1800579^1,2,,4	C,F	Hemolytic uremic syndrome atypical 6 (AHUS6)⁴ --	22978279(-)	`GACGCC/TCGGCT`	2	P L	mis¹		3		NA	2646
rs1800578^1,2,,4	C,F	Hemolytic uremic syndrome atypical 6 (AHUS6)⁴ other¹	22978298(-)	`GCGAGC/TCCCCG`	2	P S	mis¹		2		NA	3020
rs41348347^1,2,,4	C	Thrombophilia due to thrombomodulin defect (THPH12)⁴ unknown¹	22978325(-)	`AGGTGG/TACGGT`	2	D Y	mis¹		3		NA	50
rs1800576^1,2,,4	C	Hemolytic uremic syndrome atypical 6 (AHUS6)⁴ other¹	22979654(-)	`GCCCCG/ACGACC`	2	/T /A	mis¹		1		EU	205
VAR_063223⁴		Hemolytic uremic syndrome atypical 6 (AHUS6)⁴	--	see VAR_063223	2	D G	mis⁴		0	--	--	--	--
VAR_063673⁴		Hemolytic uremic syndrome atypical 6 (AHUS6)⁴	--	see VAR_063673	2	D E	mis⁴		0	--	--	--	--
VAR_063674⁴		Hemolytic uremic syndrome atypical 6 (AHUS6)⁴	--	see VAR_063674	2	A G	mis⁴		0	--	--	--	--
VAR_063224⁴		Hemolytic uremic syndrome atypical 6 (AHUS6)⁴	--	see VAR_063224	2	V L	mis⁴		0	--	--	--	--
rs3176139^1,2	C,F	--	22975473(-)	`GCTCCA/GTGCAC`	1	--	ds500¹		2		NS	80
rs139307535^1,2	C	--	22975486(+)	`CCCAG-/CACACAC`	1	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for THBD (23026270 - 23030378 bp)

Structural Variations
Database of Genomic Variants (DGV) 3 variations for THBD: About this table

Variant ID	Type	Subtype	PubMed ID
nsv912816	CNV	Gain	21882294
nsv482065	CNV	Gain	20164927
dgv1317e1	CNV	Complex	17122850

Human Gene Mutation Database (HGMD): THBD

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing THBD

DNA2.0 Custom Variant and Variant Library Synthesis for THBD

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 188040
OMIM disorders: 614486 612926
UniProtKB/Swiss-Prot: TRBM_HUMAN, P07204

Thrombophilia due to thrombomodulin defect (THPH12) [MIM:614486]: A hemostatic disorder characterized by

a tendency to thrombosis. 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Other genes may play a role in modifying the phenotype

Selected diseases for THBD (see all 214):
About MalaCards

thrombophilia due to thrombomodulin defect thbd-related atypical hemolytic-uremic syndrome eisenmenger syndrome mercury poisoning

dengue shock syndrome hemolytic uremic syndrome, atypical 6 malignant biphasic mesothelioma disseminated intravascular coagulation

carotid artery occlusion sarcomatoid mesothelioma thromboembolism legg-calve-perthes disease

plasmodium vivax malaria thrombotic thrombocytopenic purpura meningococcemia churg-strauss syndrome

adenomatoid tumor pericardial mesothelioma malignant mesothelioma erythromelalgia

10 diseases from the University of Copenhagen DISEASES database for THBD:

Disseminated intravascular coagulation Vascular disease Benign mesothelioma Malignant mesothelioma

Protein C deficiency Heart disease hemolytic-uremic syndrome Lupus erythematosus

Kidney disease Connective tissue disease

THBD for disorders About GeneDecksing

Congresses - knowledge worth sharing:
The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014

Selected Novoseek inferred disease relationships for THBD gene (see all 97) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
cell damage	78.4	130	8864450 (3), 17401180 (2), 10420077 (2), 10077454 (2) (see all 91)
disseminated intravascular coagulation	76.1	50	18431261 (5), 15650541 (2), 1660674 (2), 8236161 (2) (see all 28)
thrombosis	75.9	96	10685802 (4), 1651429 (3), 10460600 (3), 7737745 (2) (see all 57)
thrombophilia	74.5	30	9198186 (3), 7822946 (2), 10102456 (1), 11020468 (1) (see all 22)
epithelial mesothelioma	72.2	4	9253621 (1), 7684019 (1), 8884348 (1), 11381372 (1)
mesothelioma	64.6	65	10697265 (3), 12605647 (3), 9253621 (2), 11145250 (2) (see all 33)
apc resistance	63	8	15100907 (1), 11754415 (1), 17549295 (1), 19253106 (1) (see all 6)
protein c deficiency	62.5	4	2167370 (1), 9712290 (1), 8163684 (1)
malignant mesothelioma	62.4	11	8884348 (3), 9570213 (1), 10649525 (1), 11895489 (1) (see all 9)
coagulopathy	61.5	8	8752515 (1), 10810213 (1), 17239427 (1), 12211414 (1) (see all 6)

Genatlas disease: THBD

thrombosis,recurrent

GeneTests: THBD
GeneReviews: THBD
Genetic Association Database (GAD): THBD
Human Genome Epidemiology (HuGE) Navigator: THBD (55 documents)

Export disorders for THBD gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for THBD gene, integrated from 10 sources (see all 1620):
(articles sorted by number of sources associating them with THBD)

Utopia: connect your pdf to the dynamic
world of online information

Thrombomodulin mutations in atypical hemolytic-uremic syndrome. (PubMed id 19625716)^{1, 2, 4, 9} Delvaeye M.... Conway E.M. (N. Engl. J. Med. 2009)
Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia. (PubMed id 12139752)^{1, 2, 4, 9} Faioni E.M.... Rodeghiero F. (Br. J. Haematol. 2002)
Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease. (PubMed id 11245641)^{1, 2, 4, 9} Wu K.K.... Juneja H. (Circulation 2001)
Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. (PubMed id 20513133)^{1, 2, 4} Maga T.K.... Smith R.J.H. (Hum. Mutat. 2010)
A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. (PubMed id 9157575)^{1, 2, 4} Norlund L.... Oehlin A.-K. (Thromb. Haemost. 1997)
Gene structure of human thrombomodulin, a cofactor for thrombin- catalyzed activation of protein C. (PubMed id 2836377)^{1, 2, 7} Shirai T.... Suzuki K. (J. Biochem. 1988)
Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss. (PubMed id 11552992)^{1, 4, 9} Franchi F....Faioni E.M. (Br. J. Haematol. 2001)
Variations in the thrombomodulin and endothelial protein C receptor genes in couples with recurrent miscarriage. (PubMed id 17099210)^{1, 4, 9} Kaare M....AittomAoki K. (Hum. Reprod. 2007)
Thrombomodulin gene variations and thromboembolic disease. (PubMed id 9198186)^{1, 2, 9} Oehlin A.-K.... Marlar R.A. (Thromb. Haemost. 1997)
Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population. (PubMed id 16507317)^{1, 4, 9} Sugiyama S....Miyata T. (Thromb. Res. 2007)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 7056	HGNC: 11784	AceView: THBD	Ensembl:ENSG00000178726	euGenes: HUgn7056
ECgene: THBD	Kegg: 7056	H-InvDB: THBD

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for THBD	Pharmacogenomics, SNPs, Pathways
Wikipedia	http://en.wikipedia.org/wiki/Thrombomodulin
SeattleSNPs	http://pga.gs.washington.edu/data/thbd/
Functional Glycomics Gateway - Glycan Binding	http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_211

Intellectual Property for THBD gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for THBD gene:
Search GeneIP for patents involving THBD

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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THBD Gene

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PT PROLONGED
Microalbuminuria
Collagen Diseases
Hemorrhagic diseases
sepsis
Raynauds Phenomenon
veno-occlusive disease
essential hypertension
UREMIC SYNDROME
coagulopathy
Acute myocardial infarction
ADENOCARCINOMA LUNG
Primary pulmonary hypertension
Atherosclerosis
Purpura Thrombotic Thrombocytopenic
Respiratory Distress Syndrome
Antiphospholipid Syndrome
Deep vein thrombosis
Hypercholesterolemia
Adenocarcinoma
cell damage
Carcinoma Transitional Cell
Hypertension Pulmonary
Brenner Tumor
Thrombocytopenia
Erythromelalgia
Coronary Atherosclerosis
Myeloproliferative Disorders
RENAL DISEASE
Cerebral Infarction
ARTERIAL THROMBOSIS
Protein C Deficiency
Inflammation
Diabetic Nephropathies
Microangiopathy Diabetic
Monocytic leukemia
Hyperhomocysteinemia
LACUNE
Cardiovascular Diseases
Malignant mesothelioma
Tumors
Thrombosis
Mediterranean Spotted Fever
Meningococcemia
Necrosis
Preeclampsia
Disseminated Intravascular Coagulation
Dengue Shock Syndrome
Coronary Heart Disease
Shock Septic
Thrombocytosis
APC Resistance
HYPERTENSION ARTERIAL
Vasculitis
Eisenmenger Syndrome
Venous Thrombosis
atherosclerotic plaque
Systemic Inflammatory Response Syndrome
Diabetic Angiopathies
Eclampsia
retinopathy
Infarction Lacunar
POADS
Churg-Strauss Syndrome
Atypical Hemolytic-Uremic Syndrome
Diabetes Mellitus
Arterial Occlusive Diseases
PLEURAL MALIGNANT MESOTHELIOMA
Pneumonia Interstitial
VENOUS OCCLUSION
Dysfibrinogenemia
BLEEDING TENDENCY
Albuminuria
Multiple Organ Failure
Polycythemia Vera
Coronary Artery Disease
Carcinoma Large Cell
Acute monocytic leukemia
stasis
Bleeding
BEHCET DISEASE
Thromboembolism Pulmonary
mesothelioma
Carcinoma Squamous Cell
Acute respiratory distress
Leukemia Promyelocytic Acute
Thrombophilia
STROKE
epithelial mesothelioma
Vascular Diseases
Lupus Nephritis
Respiratory Distress Syndrome Adult
Thrombocythemia Essential
NIDDM
Sclerosis Systemic
Thromboembolism
Lupus Erythematosus Systemic
Renal Failure Chronic

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