TBX5 T-box transcription factor 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TBX5provided by HGNC
Official Full Name: T-box transcription factor 5provided by HGNC
Primary source: HGNC:HGNC:11604
See related: Ensembl:ENSG00000089225 MIM:601620; AllianceGenome:HGNC:11604
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HOS
Summary: This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. The encoded protein may play a role in heart development and specification of limb identity. Mutations in this gene have been associated with Holt-Oram syndrome, a developmental disorder affecting the heart and upper limbs. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
Expression: Biased expression in heart (RPKM 12.5), placenta (RPKM 8.8) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.21

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (114353911..114408442, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (114330644..114385180, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (114791716..114846247, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TBX5 genetic variants and SCD-CAD susceptibility: insights from Chinese Han cohorts.
Title: TBX5 genetic variants and SCD-CAD susceptibility: insights from Chinese Han cohorts.
TBX5 variants and cardiac phenotype: A systematic review of the literature and a novel variant.
Title: TBX5 variants and cardiac phenotype: A systematic review of the literature and a novel variant.
Prioritizing cardiovascular disease-associated variants altering NKX2-5 and TBX5 binding through an integrative computational approach.
Title: Prioritizing cardiovascular disease-associated variants altering NKX2-5 and TBX5 binding through an integrative computational approach.
CircTBX5 knockdown modulates the miR-558/MyD88 axis to alleviate IL-1beta-induced inflammation, apoptosis and extracellular matrix degradation in chondrocytes via inactivating the NF-kappaB signaling.
Title: CircTBX5 knockdown modulates the miR-558/MyD88 axis to alleviate IL-1β-induced inflammation, apoptosis and extracellular matrix degradation in chondrocytes via inactivating the NF-κB signaling.
hsa_circ_0038382 upregulates T-box transcription factor 5 to inhibit keloid formation by interacting with miR-940.
Title: hsa_circ_0038382 upregulates T-box transcription factor 5 to inhibit keloid formation by interacting with miR-940.
Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves.
Title: Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves.
TBX5 variant with the novel phenotype of mixedtype total anomalous pulmonary venous return in HoltOram Syndrome and variable intrafamilial heart defects.
Title: TBX5 variant with the novel phenotype of mixed‑type total anomalous pulmonary venous return in Holt‑Oram Syndrome and variable intrafamilial heart defects.
Identification of a novel TBX5 c.755 + 1 G > A variant and related pathogenesis in a family with Holt-Oram syndrome.
Title: Identification of a novel TBX5 c.755 + 1 G > A variant and related pathogenesis in a family with Holt-Oram syndrome.
Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.
Title: Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.
MicroRNA-603 Promotes Progression of Cutaneous Melanoma by Regulating TBX5.
Title: MicroRNA-603 Promotes Progression of Cutaneous Melanoma by Regulating TBX5.

Submit: New GeneRIF Correction See all GeneRIFs (110)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Holt-Oram syndrome MedGen: C0265264 OMIM: 142900 GeneReviews: Holt-Oram Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-07-29) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-07-29) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies of the PR interval in African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of blood pressure and hypertension. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of PR interval. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of a novel percent mammographic density locus at 12q24. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts. EBI GWAS Catalog EBI GWAS CatalogPubMed
Several common variants modulate heart rate, PR interval and QRS duration. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-150881 (e-PCR)
- UniSTS:173599

D12S1646 (e-PCR)
- UniSTS:8775

RH70967 (e-PCR)
- UniSTS:49097

TBX5_2215 (e-PCR)
- UniSTS:281045

RH103950 (e-PCR)
- UniSTS:98275

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in atrial septum morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in atrioventricular bundle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in atrioventricular node cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in atrioventricular node cell fate commitment	ISS Inferred from Sequence or Structural Similarity more info
involved_in atrioventricular valve morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_positive_effect bundle of His cell to Purkinje myocyte communication by electrical coupling	ISS Inferred from Sequence or Structural Similarity more info
involved_in bundle of His development	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac left ventricle formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cardiac left ventricle formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in cell fate specification	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell migration involved in coronary vasculogenesis	TAS Traceable Author Statement more info	PubMed
involved_in cell-cell signaling	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_positive_effect cell-cell signaling involved in cardiac conduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in embryonic forelimb morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic limb morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endocardial cushion development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within forelimb morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart development	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within heart development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in morphogenesis of an epithelium	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cardiac muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of epithelial to mesenchymal transition	TAS Traceable Author Statement more info	PubMed
involved_in pattern specification process	IBA Inferred from Biological aspect of Ancestor more info
involved_in pericardium development	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of cardiac conduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cardiac muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cardioblast differentiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of cell communication by electrical coupling involved in cardiac conduction	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of gap junction assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of secondary heart field cardioblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_positive_effect regulation of atrial cardiac muscle cell membrane depolarization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in sinoatrial node development	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in ventricular septum development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of chromatin	IBA Inferred from Biological aspect of Ancestor more info
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-DNA complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: T-box transcription factor TBX5

Names: T-box 5; T-box protein 5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007373.1 RefSeqGene

Range

5001..59513

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_670

mRNA and Protein(s)

NM_000192.3 → NP_000183.2 T-box transcription factor TBX5 isoform 1

See identical proteins and their annotated locations for NP_000183.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 4 both encode the same isoform (1).

Source sequence(s)

AC009260, AF221714, BC027942, DA863182

Consensus CDS

CCDS9173.1

UniProtKB/Swiss-Prot

A6ND77, O15301, Q96TB0, Q99593, Q9Y4I2

UniProtKB/TrEMBL

A8K3J6

Related

ENSP00000309913.4, ENST00000310346.8

Conserved Domains (1) summary

cd20189
Location:54 → 238

T-box_TBX4_5-like; DNA-binding domain of T-box transcription factor 4 and 5, and related T-box proteins
NM_080717.4 → NP_542448.1 T-box transcription factor TBX5 isoform 3

See identical proteins and their annotated locations for NP_542448.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks the exon containing the translation start site compared to transcript variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AB051068, AC009260, AF221714, BC027942

Consensus CDS

CCDS9174.1

UniProtKB/TrEMBL

A8K3J6

Related

ENSP00000337723.5, ENST00000349716.9

Conserved Domains (1) summary

cd20189
Location:4 → 188

T-box_TBX4_5-like; DNA-binding domain of T-box transcription factor 4 and 5, and related T-box proteins
NM_181486.4 → NP_852259.1 T-box transcription factor TBX5 isoform 1

See identical proteins and their annotated locations for NP_852259.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1 and 4 both encode the same isoform (1).

Source sequence(s)

AC009260, BC027942, CB960757

Consensus CDS

CCDS9173.1

UniProtKB/Swiss-Prot

A6ND77, O15301, Q96TB0, Q99593, Q9Y4I2

UniProtKB/TrEMBL

A8K3J6

Related

ENSP00000384152.3, ENST00000405440.7

Conserved Domains (1) summary

cd20189
Location:54 → 238

T-box_TBX4_5-like; DNA-binding domain of T-box transcription factor 4 and 5, and related T-box proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

114353911..114408442 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017019912.2 → XP_016875401.1 T-box transcription factor TBX5 isoform X1

UniProtKB/TrEMBL

A8K3J6

Conserved Domains (1) summary

cd00182
Location:69 → 257

TBOX; T-box DNA binding domain of the T-box family of transcriptional regulators. The T-box family is an ancient group that appears to play a critical role in development in all animal species. These genes were uncovered on the basis of similarity to the DNA ...

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

114330644..114385180 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_080718.1: Suppressed sequence

Description

NM_080718.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.