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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TTR Gene

protein-coding GIFtS: 68
GCID: GC18P029194

transthyretin

(Previous names: prealbumin, amyloidosis type I )
(Previous symbol: PALB)

Explore 180 diseases affiliated with
TTR via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Transthyretin¹		CTS²
PALB¹ ² ³ ⁵		CTS1²
HsT2651¹ ²		Carpal Tunnel Syndrome 1²
Prealbumin, Amyloidosis Type I¹ ²		Thyroxine-Binding Prealbumin²
ATTR² ³		Prealbumin³
TBPA² ³

External Ids:	HGNC: 12405¹	Entrez Gene: 7276²	Ensembl: ENSG00000118271⁷	OMIM: 176300⁵	UniProtKB: P02766³

Export aliases for TTR gene to outside databases

Previous GC identifers: GC18P028991 GC18P027423 GC18P027425 GC18P026028

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TTR:

This gene encodes transthyretin, one of the three prealbumins including alpha-1-antitrypsin, transthyretin and

orosomucoid. Transthyretin is a carrier protein; it transports thyroid hormones in the plasma and cerebrospinal fluid,

and also transports retinol (vitamin A) in the plasma. The protein consists of a tetramer of identical subunits. More

than 80 different mutations in this gene have been reported; most mutations are related to amyloid deposition,

affecting predominantly peripheral nerve and/or the heart, and a small portion of the gene mutations is

non-amyloidogenic. The diseases caused by mutations include amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia,

amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis,

carpal tunnel syndrome, etc. (provided by RefSeq, Jan 2009)

UniProtKB/Swiss-Prot: TTHY_HUMAN, P02766

Function: Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain

Gene Wiki entry for TTR (Transthyretin)

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000018.9 NC_018929.1 NT_010966.14

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TTR gene promoter:
MEF-2 Meis-1b CREB MEF-2A deltaCREB aMEF-2 Meis-1a Meis-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TTR promoter sequence

Search SABiosciences Chromatin IP Primers for TTR

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TTR

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

Entrez Gene cytogenetic band: 18q12.1 Ensembl cytogenetic band: 18q12.1 HGNC cytogenetic band: 18q12.1

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

GeneLoc information about chromosome 18 GeneLoc Exon Structure

GeneLoc location for GC18P029194: view genomic region (about GC identifiers)

Start:	29,171,689 bp from pter	End:	29,178,987 bp from pter
Size:	7,299 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TTHY_HUMAN, P02766 (See protein sequence)

Recommended Name: Transthyretin precursor

Size: 147 amino acids; 15887 Da

Subunit: Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can

accommodate two ligand molecules. Interacts with RBP4

Subcellular location: Secreted. Cytoplasm

Miscellaneous: Tetramer dissociation and partial unfolding leads to the formation of aggregates and amyloid fibrils.

Small molecules that occupy at least one of the thyroid hormone binding sites stabilize the tetramer, and thereby

stabilize the native state and protect against misfolding and the formation of amyloid fibrils

Miscellaneous: Two binding sites for thyroxine are located in the channel. Less than 1% of plasma prealbumin molecules

are normally involved in thyroxine transport. L-thyroxine binds to the transthyretin by an order of magnitude stronger

than does the triiodo-L-thyronine. Thyroxine-binding globulin is the major carrier protein for thyroid hormones in man

Miscellaneous: About 40% of plasma transthyretin circulates in a tight protein-protein complex with the plasma

retinol-binding protein (RBP). The formation of the complex with RBP stabilizes the binding of retinol to RBP and

decreases the glomerular filtration and renal catabolism of the relatively small RBP molecule. There is evidence for 2

binding sites for RBP, one possibly being a region that includes Ile-104, located on the outer surface of the

transthyretin molecule

6/174 PDB 3D structures from and Proteopedia for TTR (see all 174):

1BM7 (3D)

1BMZ (3D)

1BZ8 (3D)

1BZD (3D)

1BZE (3D)

1DVQ (3D)

Secondary accessions: Q549C7 Q6IB96 Q9UBZ6 Q9UCM9

Explore the universe of human proteins at neXtProt for TTR: NX_P02766

Post-translational modifications:

Not glycosylated under normal conditions. Following unfolding, caused for example by variant AMYL-TTR 'Gly-38', the

cryptic Asn-118 site is exposed and glycosylated by STT3B-containing OST complex, leading to its degradation by the

ER-associated degradation (ERAD) pathway¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P02766

TTR Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000362.1

ENSEMBL proteins:

ENSP00000237014

Reactome Protein details: P02766
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
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	Novus Biologicals TTR Proteins Novus Biologicals TTR Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for TTR

Gene Ontology (GO): 4 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	--
GO:0005615	extracellular space	IEA	--
GO:0005737	cytoplasm	IEA	--
GO:0043234	protein complex	IEA	--

TTR for ontologies About GeneDecksing

TTR Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TTR
	R&D Systems Antibodies for TTR (Transthyretin/Prealbumin)
	OriGene Antibodies (see all 4): TTR OriGene Custom Antibody Services for TTR
	GenScript Superior Antibodies for TTR
	Novus Biologicals TTR Antibodies
	Abcam antibodies for TTR
	Uscn Antibodies for TTR
	ThermoFisher Antibodies for TTR

Assay Products for TTR:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for TTR
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for TTR

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TTR for domains About GeneDecksing

4 InterPro domains/families:

IPR023416 Transthyretin/HIU_hydrolase_SF

IPR023419 Transthyretin_CS

IPR000895 Transthyretin/HIU_hydrolase

IPR023418 Thyroxine_BS

Graphical View of Domain Structure for InterPro Entry P02766

ProtoNet protein and cluster: P02766

1 Blocks protein family: IPB000895 Transthyretin

UniProtKB/Swiss-Prot: TTHY_HUMAN, P02766

Domain: Each monomer has two 4-stranded beta sheets and the shape of a prolate ellipsoid. Antiparallel beta-sheet

interactions link monomers into dimers. A short loop from each monomer forms the main dimer-dimer interaction. These

two pairs of loops separate the opposed, convex beta-sheets of the dimers to form an internal channel

Similarity: Belongs to the transthyretin family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TTHY_HUMAN, P02766

Function: Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain

Genatlas biochemistry entry for TTR:

transthyretin (prealbumin)

miRNA Products:		OriGene 3'-UTR Clone: TTR Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TTR
		4 QIAGEN miScript miRNA Assays for microRNAs that regulate TTR:
		hsa-miR-141 hsa-miR-593 hsa-miR-200a hsa-miR-570
		SwitchGear 3'UTR luciferase reporter plasmid: TTR 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TTR (see all 7) OriGene shRNA RFP: TTR OriGene siRNA: TTR
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TTR

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TTR

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
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		GenScript: all cDNA clones in your preferred vector: TTR (NM_000371)
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Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TTR
		LifeMap BioReagents: cell lines associated with TTR: Choroid Plexus Package T42, PureStem ES-210, Ecto-ntu Progenitor

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TTR

Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005179	hormone activity	IEA	--
GO:0005515	protein binding	IPI	986177
GO:0042562	hormone binding	IEA	--
GO:0046982	protein heterodimerization activity	IEA	--

TTR for ontologies           About GeneDecksing

Animal Models:
     Mouse knock-outs for TTR: Ttr^tm1Wsb Ttr^tm1Kymm
     3 MGI mutant phenotypes (inferred from 7 alleles) (MGI details for Ttr):

homeostasis/metabolism

no phenotypic analysis

vision/eye

TTR for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/9 super-pathways (see all 9) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Retinoid metabolism and transport

	Retinoid metabolism and transport	1.00			Diseases associated with visual transduction	0.73
	Visual phototransduction	0.74

Amyloid precursor proteins form ordered fibrils

Amyloid precursor proteins form ordered fibrils

1.00

Amyloids

0.43

Disease

Disease

1.00

Visual Cycle in Retinal Rods

Visual Cycle in Retinal Rods

1.00

FOXA2 and FOXA3 transcription factor networks

FOXA2 and FOXA3 transcription factor networks

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

1 Downloadable PowerPoint Slide of QIAGEN Pathway Central Maps for TTR

Visual Cycle in Retinal Rods

1 BioSystems Pathway for TTR

FOXA2 and FOXA3 transcription factor networks

5/10 Reactome Pathways for TTR (see all 10)

	Amyloids
	Diseases associated with visual transduction
	Amyloid precursor proteins form ordered fibrils
	Retinoid cycle disease events
	Retinoid metabolism and transport

TTR for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TTR

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/82 Interacting proteins for TTR (P02766^{2, 3} ENSP00000237014⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 82)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
VIM	P08670²^,³, ENSP00000224237⁴	MINT-63350 MINT-8275998 I2D: score=5 STRING: ENSP00000224237
AGER	Q15109²^,³, ENSP00000364217⁴	MINT-2635425 MINT-2635447 I2D: score=2 STRING: ENSP00000364217
CHD3	Q12873²^,³	MINT-8275754 MINT-63352 I2D: score=5
FEZ1	Q99689²^,³	MINT-63351 MINT-8275796 I2D: score=5
SETDB1	Q15047²^,³	MINT-63347 MINT-8275913 I2D: score=5

About this table

Gene Ontology (GO): 2 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006810	transport	IEA	--
GO:0042572	retinol metabolic process	IEA	--

TTR for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TTR for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for TTR

3 HMDB Compounds for TTR About this table

Compound	Synonyms	CAS #	PubMed Ids
Dimethyl sulfoxide	(methylsulfinyl)methane;Dimethyl sulfoxide (see all 5)	67-68-5	--
Liothyronine	3,3',5-Triiodo-L-thyronine (see all 20)	6893-02-3	--
Thyroxine	(-)-Thyroxine (see all 33)	51-48-9	--

10/45 DrugBank Compounds for TTR (see all 45) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Diflunisal	--	22494-42-4	carrier	--	15689188 14711308 14968122 17028027 15080795
Flufenamic Acid	--	530-78-9	carrier	--	17139284 14968122 17016423 10592235 15080795
3',5'-Dinitro-N-Acetyl-L-Thyronine	--	--	carrier	--	17139284 17016423 10592235
3,3',5,5'-Tetraiodothyroacetic Acid	--	--	carrier	--	17139284 17016423 10592235
Dibenzofuran-4,6-Dicarboxylic Acid	--	--	carrier	--	17139284 17016423 10592235
N-(M-Trifluoromethylphenyl) Phenoxazine-4,6-Dicarboxylic Acid	--	--	carrier	--	17139284 17016423 10592235
O-Trifluoromethylphenyl Anthranilic Acid	--	--	carrier	--	17139284 17016423 10592235
2,4,6-Tribromophenol	--	118-79-6	carrier	--	17139284 17016423
Diclofenac	Diclofenac Acid (see all 4)	15307-86-5	carrier	--	14968122 15080795
Levothyroxine	(-)-Thyroxine (see all 13)	51-48-9	carrier	--	15082720 12553433

10/118 Novoseek chemical compound relationships for TTR gene (see all 118) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
vitamin a	84.1	646	19021760 (8), 9772136 (7), 10953676 (7), 16317126 (6) (see all 99)
thyroxine	79.4	417	2393944 (6), 8039542 (5), 1979335 (4), 11468389 (3) (see all 99)
stresson	74.4	1	12236086 (1)
diflunisal	67.2	53	17107884 (7), 15080795 (6), 14711308 (2), 17028027 (2) (see all 12)
4'-iodo-4'-deoxydoxorubicin	58.4	11	10998371 (4), 7708755 (1), 10854215 (1), 16266291 (1) (see all 5)
valine	57.9	35	1544214 (2), 7914929 (1), 9840068 (1), 2002274 (1) (see all 23)
pentabromophenol	55.6	5	10957627 (2)
3,3'-diiodo-l-thyronine	55.6	1	1730601 (1)
thioflavin t	51.5	5	11306576 (1), 14592420 (1), 8634341 (1), 18162431 (1)
triiodothyronine	50.8	50	16879610 (3), 2109784 (2), 1700701 (1), 8156097 (1) (see all 22)

Search CenterWatch for drugs/clinical trials and news about TTR / TTHY

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TTR gene:

NM_000371.3

Unigene Cluster for TTR:

Transthyretin

Hs.427202 [show with all ESTs]

Unigene Representative Sequence: BE742013

3 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000237014(uc002kwx.4) ENST00000432547 ENST00000541025

miRNA Products:		OriGene 3'-UTR Clone: TTR Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TTR
		4 QIAGEN miScript miRNA Assays for microRNAs that regulate TTR:
		hsa-miR-141 hsa-miR-593 hsa-miR-200a hsa-miR-570
		SwitchGear 3'UTR luciferase reporter plasmid: TTR 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TTR

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TTR (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TTR OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TTR (NM_000371)
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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TTR
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TTR

Additional cDNA sequence:

AF162690.1 AK312051.1 BC005310.1 BC020791.1 BT007189.1 CR456908.1 D00096.1 DQ839490.1

GU727633.1 K02091.1 M10605.1 M11714.1 U19780.1 X59498.1

24/28 DOTS entries (see all 28):

DT.100045780 DT.100893448 DT.99949554 DT.100893449 DT.100893460 DT.100893447 DT.121106434 DT.92468651

DT.121106417 DT.320451 DT.100893450 DT.92468671 DT.100893452 DT.91775637 DT.95371616 DT.100664681

DT.100893459 DT.95371447 DT.100893453 DT.100893461 DT.121106401 DT.121106403 DT.121106410 DT.121106428

24/2837 AceView cDNA sequences (see all 2837):

BI712420 BQ269326 BQ635884 BQ777101 BU790034 CA941270 BM310904 CA950242

M11714 BQ416869 BM312612 BQ269715 BM505091 BI438421 CA848213 BM314769

CA776579 BU949913 BU949197 R97313 BQ271550 CA947127 CA773973 BM312786

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for TTR About this scheme

ExUns:	1a	·	1b	^	2a	·	2b	^	3a	·	3b	^	4a	·	4b
SP1:									-
SP2:
SP3:							-		-

ECgene alternative splicing isoforms for TTR

(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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TTR expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TAACCAAGAG

About this image

TTR expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

10/23 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 23)

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Brain

Choroid Plexus

Choroid Plexus Progenitor Cells

Selective marker (cell-identifying gene)

Choroid Plexus

Brain

Choroid Plexus

Mature Choroid Plexus Cells

Choroid Plexus

Eye

Retinal Pigmented Epithelium

Mature Retinal Pigmented Epithelium Cells

Retinal Pigmented Epithelium

Gut Tube

Ventral Foregut Endoderm

Hepatic Endoderm Cells

Liver

Liver Bud

Hepatoblasts

Liver

Epiblast

Intraembryonic Epiblast Cells

Early Embryo

Gut Tube

Foregut

Foregut Endoderm Cells

Endoderm

Gut Tube

Ventral Foregut Endoderm

Ventral Foregut Endoderm Cells

Endoderm

Hypoblast

Extraembryonic Endoderm

Extraembryonic Endoderm Cells

Extraembryonic Tissues, Yolk Sac

Hypoblast

Extraembryonic Visceral Endoderm

Extraembryonic Visceral Endoderm Cells

Extraembryonic Tissues, Yolk Sac

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 9 LifeMap Cells

Name

Category

Sclerotome cells (Primary Cell)

Bone, Cartilage, Somite

CPEC (Generation of choroi...)

Hepatocyte-like cells (Mouse embryonic stem...)

Immature hepatocyte-like cells (Generation of hepato...)

Midbrain dopaminergic-like neurons (Generation of midbra...)

Endoderm progenitor-like cells (Generation and expan...)

Embryoid bodies (Two-step protocol fo...)

Cardiomyocyte-like progenitor cells (Derivation of cardio...)

DKK1-induced cells (Derivation of cardio...)

See TTR Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TTR

SOURCE GeneReport for Unigene cluster: Hs.427202

UniProtKB/Swiss-Prot: TTHY_HUMAN, P02766

Tissue specificity: Detected in serum and cerebrospinal fluid (at protein level). Highly expressed in choroid plexus

epithelial cells. Detected in retina pigment epithelium and liver

SABiosciences Custom PCR Arrays for TTR

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TTR Browse OriGene validated miRNA SYBR primer pairs
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(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)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for TTR gene from 10/24 species (see all 24) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Ttr^{1 , 5}	transthyretin^{1, 5}	82.19(n)¹ 82.19(a)¹		18 (11.47 cM)⁵ 22139¹ NM_013697.5¹ NP_038725.1¹ 20665250⁵
chicken (Gallus gallus)	Aves	TTR¹	transthyretin	73.47(n) 74.83(a)		396277 NM_205335.2 NP_990666.1
lizard (Anolis carolinensis)	Reptilia	TTR⁶	--	64(a)	1 ↔ 1	GL343207.1(3774569-3780103)
African clawed frog (Xenopus laevis)	Amphibia	LOC397787²	transthyretin	71.16(n)		AB026996.1
zebrafish (Danio rerio)	Actinopterygii	ttr¹	transthyretin (prealbumin, amyloidosis type I)	56.45(n) 51.09(a)		449556 NM_001005598.2 NP_001005598.2
fruit fly (Drosophila melanogaster)	Insecta	CG30016⁶	--	25(a)	1 ↔ 1	2R(6762397-6762897)
worm (Caenorhabditis elegans)	Secernentea	R09H10.3⁶ ZK697.8⁶	Probable 5-hydroxyisourate hydrolase ZK697.8	25(a) 24(a)	many → 1 many → 1	IV(10606934-10608834) V(1748432-1749153)
thale cress (Arabidopsis thaliana)	eudicotyledons	TTL⁶	uric acid degradation bifunctional protein TTL	10(a)	1 ↔ 1	5(23554386-23555883)
rice (Oryza sativa)	Liliopsida	--	steroid binding protein, putative, expressed	9(a)	1 ↔ 1	3(15647548-15650804)
E. coli (Escherichia coli)	Gamma proteobacteria	hiuH⁶	Hydroxyisourate hydrolase	26(a)	1 ↔ 1	Chromosome(2036980-2037393)

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for TTR gene

LOC100130015²

1 SIMAP similar gene for TTR using alignment to 3 protein entries: TTHY_HUMAN (see all proteins):

transthyretin/ TTR

TTR for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 18 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs36204272^1,2	C,F,	non-pathogenic	56766210(+)	`GATCTG/CTCTGT`	1	--	int¹		5		EU NA WA	786
rs1800458^1,2	C,F,O,H,	non-pathogenic	56771858(+)	`GCACCG/AGTGAA`	2	/S /G	mis¹ ese³		22		NA NS EA EU	8317
rs76992529^1,2	C,F,	pathogenic	56766105(+)	`CTGTCG/ATCACC`	2	/I /V	mis¹		2		WA NA	4670
rs28933981^1,2	C,F,	pathogenic	56766113(+)	`CACCAC/TGGCTG`	2	T M	mis¹ ese³		3		NA EU	6301
rs121918095^1,2	C,	pathogenic	56766158(+)	`CCGCCA/GCTACA`	2	H R	mis¹		0	--	--	--	--
rs121918069^1,2	C	pathogenic	56769608(+)	`TGGGCA/G/TCACAA`	3	H R L	mis¹		0	--	--	--	--
rs11541796^1,2	C	pathogenic	56771749(+)	`CTGGGA/GGCCAT`	2	E G	mis¹		0	--	--	--	--
rs121918068^1,2	C	pathogenic	56771777(+)	`ATGTGA/C/TTCAGA`	3	I L F	mis¹		0	--	--	--	--
rs79977247^1,2	C,	pathogenic	56771785(+)	`GGCCGC/G/TGCATG`	3	A G V	mis¹		0	--	--	--	--
rs28933979^1,2	C	pathogenic	56771786(+)	`TGGCCA/C/GTGCAT`	3	M L V	mis¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for TTR (29171689 - 29178987 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for TTR: --
Human Gene Mutation Database (HGMD): TTR

Locus Specific Mutation Databases (LSDB): TTR

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TTR

DNA2.0 Custom Variant and Variant Library Synthesis for TTR

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TTR for disorders           About GeneDecksing

OMIM gene information: 176300
OMIM disorders: 105210  145680  115430
UniProtKB/Swiss-Prot: TTHY_HUMAN, P02766

Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:105210]. A hereditary

generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading

to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The

disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous

system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and

subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment

(oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor

deterioration, variable amyloid deposition in the vitreous humor

Defects in TTR are a cause of hyperthyroxinemia dystransthyretinemic euthyroidal (HTDE) [MIM:145680]. It is a

condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable

binding protein abnormalities

Defects in TTR are a cause of carpal tunnel syndrome type 1 (CTS1) [MIM:115430]. It is a condition

characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and

paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of

sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be

associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis

20/180 diseases for TTR (see all 180): About MalaCards

carpal tunnel syndrome amyloidosis polyneuropathy protein-energy malnutrition

molybdenum cofactor deficiency open-angle glaucoma carpal tunnel syndrome, familial cardiomyopathy

finnish type amyloidosis transthyretin amyloidosis cerebral amyloid angiopathy spinal cord injury

dystransthyretinemic hyperthyroxinemia congenital nephrotic syndrome finnish type familial oculoleptomeningeal amyloidosis avascular necrosis of femoral head

dysalbuminemic hyperthyroxinemia hypervitaminosis a familial transthyretin amyloidosis primary open angle glaucoma

14 diseases from the University of Copenhagen DISEASES database for TTR:

Polyneuropathy Amyloidosis protein-energy malnutrition Carpal tunnel syndrome

Hyperthyroxinemia Autonomic neuropathy Kidney failure Neuropathy

Liver disease Alzheimer's disease Cancer Diarrhea

Choroid plexus papilloma Hypothyroidism

10/98 Novoseek disease relationships for TTR gene (see all 98) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
familial amyloid polyneuropathies	95.9	190	9922152 (2), 19279259 (2), 10506096 (2), 16751191 (2) (see all 99)
amyloidosis	91.9	665	19075702 (8), 18537267 (6), 19664600 (5), 10827225 (5) (see all 99)
amyloid neuropathies	91.5	40	10882995 (3), 20373457 (3), 11523162 (2), 8509786 (2) (see all 26)
polyneuropathy	91.2	380	10919188 (3), 8089102 (2), 1932142 (2), 9818053 (2) (see all 99)
amyloidosis systemic	90.7	149	7474944 (3), 2349941 (2), 2015890 (2), 11409037 (2) (see all 82)
amyloidosis hereditary	90.6	38	1301926 (2), 9090525 (2), 12376880 (1), 8810738 (1) (see all 22)
amyloidosis, leptomeningeal	86.9	13	20462362 (3), 18579156 (1), 16399646 (1), 16690499 (1) (see all 7)
amyloidosis familial	86.7	35	8873510 (2), 10439117 (2), 1570831 (1), 8203468 (1) (see all 19)
type i familial amyloid polyneuropathy	86.5	18	10506096 (2), 1858483 (1), 15116456 (1), 9988146 (1) (see all 12)
amyloid deposition	85.4	73	9232027 (3), 19790249 (3), 10071047 (2), 18369743 (2) (see all 41)

GeneTests: TTR

Familial Transthyretin Amyloidosis

Genetic Association Database (GAD): TTR
Human Genome Epidemiology (HuGE) Navigator: TTR (23 documents)

Export disorders for TTR 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)
About This Section

PubMed articles for TTR gene, integrated from 9 sources (see all 1760):
(articles sorted by number of sources associating them with TTR)

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

A new transthyretin mutation associated with amyloid cardiomyopathy. (PubMed id 1570831)^{1, 2, 4, 9} Saraiva M.J.M.... Goodman D.S. (1992)
A novel transthyretin mutation at position 30 (Leu for Val) associated with familial amyloidotic polyneuropathy. (PubMed id 1520326)^{1, 2, 4, 9} Murakami T.... Ando M. (1992)
A new mutant transthyretin (Arg 10) associated with familial amyloid polyneuropathy. (PubMed id 1362222)^{1, 2, 4, 9} Uemichi T.... Benson M.D. (1992)
Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement. (PubMed id 1351039)^{1, 2, 4} Jacobson D.R.... Buxbaum J.N. (1992)
A novel transthyretin mutation associated with familial amyloidotic polyneuropathy. (PubMed id 1734866)^{1, 2, 4} Murakami T.... Araki S. (1992)
Identification of S-sulfonation and S-thiolation of a novel transthyretin Phe33Cys variant from a patient diagnosed with familial transthyretin amyloidosis. (PubMed id 12876326)^{1, 2, 9} Lim A....Costello C.E. (2003)
Amyloid fibril composition and transthyretin gene structure in senile systemic amyloidosis. (PubMed id 7474944)^{1, 2, 9} Gustavsson A....Westermark P. (1995)
Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant. (PubMed id 8038017)^{1, 2, 9} Hesse A.... Maisch B. (1993)
The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP. (PubMed id 10052934)^{1, 2, 9} Naylor H.M. and Newcomer M.E. (1999)
The Ile-84-->Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein. (PubMed id 8089102)^{1, 2, 9} Berni R....Benson M.D. (1994)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		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)
About This Section

Entrez Gene: 7276	HGNC: 12405	AceView: TTR	Ensembl:ENSG00000118271	euGenes: HUgn7276
ECgene: TTR	H-InvDB: TTR

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for TTR	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TTR
Wikipedia	http://en.wikipedia.org/wiki/Transthyretin

Intellectual Property for TTR gene
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Patent Information for TTR gene:
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GeneCards and IP:
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Severe malnutrition
Acute Disease
Protein-Energy Malnutrition
Fatal Outcome
Amyloidosis Familial
AMYLOIDOSIS SECONDARY
Phenylketonurias
Hypervitaminosis A
sepsis
involvement CNS
Cardiomyopathy Restrictive
Vitamin A Deficiency
AMYLOIDOSIS, LEPTOMENINGEAL
Choroid Plexus Tumors
Amyloid Neuropathies
Postoperative infection
Hypotension Orthostatic
Polyneuropathy
Inherited systemic amyloidosis
stage ovarian cancer
PROTEIN MALNUTRITION
Liver diseases
Intoxication
VITREOUS OPACITY
Amyloidosis
nutritional deficit
Monoclonal gammopathy
HEPATITIS ACUTE VIRAL
Late-Onset Disorders
MOLYBDENUM COFACTOR DEFICIENCY
Cardiomyopathy
RENAL DISEASE
Ependymoma
Malnutrition
Inflammation
Papilloma Choroid Plexus
iron deficiency
Proteinuria
digestive neoplasm
Hyperhomocysteinemia
Hepatitis
Anemia
Renal Failure
Intracerebral Hemorrhage
AMYLOIDOSIS NEUROPATHIC
nutritional deficiency
AUTONOMIC NEUROPATHY
familial disorder
Tumors
Liver Cirrhosis
Necrosis
Hyperthyroxinemia
Carpal Tunnel Syndrome
Senile Plaques
Type I Familial Amyloid Polyneuropathy
TBG, SERUM
Cerebral Amyloid Angiopathy
Neurodegenerative Diseases
Critically Ill
Neurological Disorders
Parkinson Disease
glaucoma
Amyloid deposition
Anorexia Nervosa
Glioma
Familial Amyloid Polyneuropathies
RENAL AMYLOIDOSIS
Hypothyroidism
Leukemia
Alzheimers Disease
Postoperative Complications
neurodegeneration
Subarachnoid Hemorrhage
hypoalbuminemia
Polyneuropathy Familial
Pressure Ulcer
Head Cancer
Familial Transthyretin Amyloidosis
Hypersensitivity Delayed
Hereditary cardiac amyloidosis
chronic pancreatitis
HEART FAILURE
FINNISH TYPE AMYLOIDOSIS
Response Acute Phase
Insulin Resistance
Respiratory disease
Liver Dysfunction
AMYLOIDOSIS PRIMARY
nutritional disorder
Amyloidosis Hereditary
Amyloidosis Systemic
ZINC DEFICIENCY
Jaundice Obstructive
HYPOCHOLESTEROLEMIA
Sensorimotor polyneuropathy
genetic disorder
DIETARY DEFICIENCY
CNS Diseases
Renal Failure Chronic

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