TBX20

Chr 7

T-box transcription factor 20

Also known as: ASD4

NCBI Gene: 57057ENSG00000164532UniProt: Q9UMR3

This gene encodes a T-box family member. The T-box family members share a common DNA binding domain, termed the T-box, and they are transcription factors involved in the regulation of developmental processes. This gene is essential for heart development. Mutations in this gene are associated with diverse cardiac pathologies, including defects in septation, valvulogenesis and cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Atrial septal defect 4MIM #611363
597
ClinVar variants
36
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TBX20
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 351 VUS of 597 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.32LOEUF
pLI 0.973
Z-score 3.72
OE 0.10 (0.04–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.68Z-score
OE missense 0.70 (0.62–0.80)
176 obs / 251.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.04–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.62–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 2 / 20.0Missense obs/exp: 176 / 251.0Syn Z: -0.60

ClinVar Variant Classifications

597 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic13
VUS351
Likely Benign205
Benign3
Conflicting2
23
Pathogenic
13
Likely Pathogenic
351
VUS
205
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
10
0
23
Likely Pathogenic
7
2
4
0
13
VUS
10
305
34
2
351
Likely Benign
0
3
67
135
205
Benign
0
0
3
0
3
Conflicting
—2
Total30310118137597

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TBX20 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TBX20-related dilated cardiomyopathy

limited
ADUndeterminedUncertain
Cardiac
G2P ↗

TBX20-related atrial septal defect

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Atrial septal defect 4

MIM #611363

Molecular basis of disorder known

📖
GeneReview available — TBX20
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Basis of Severe Childhood-Onset Cardiomyopathies.
Vasilescu C et al.·J Am Coll Cardiol
2018
Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction.
Amor-Salamanca A et al.·Circ Genom Precis Med
2024
The impact of common and rare genetic variants on bradyarrhythmia development.
Weng LC et al.·Nat Genet
2025
TBX20 loss-of-function variants in families with left ventricular non-compaction cardiomyopathy.
Chang Y et al.·J Med Genet
2024
Screening and evaluation of TBX20 and CITED2 mutations in children with congenital cardiac septal defects: Correlation with cardiac troponin T and caspase-3.
Taha M et al.·Gene
2023
The Role of TBX20 Gene Mutations in the Pathogenesis of Congenital Heart Disease: Functional Analysis and Genetic Association Study.
Liu C et al.·Cardiology
2025Meta-analysis
Tbx20 controls the expression of the KCNH2 gene and of hERG channels.
Caballero R et al.·Proc Natl Acad Sci U S A
2017
Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function.
Shen T et al.·J Clin Invest
2011Functional
Characterization of TBX20 in human hearts and its regulation by TFAP2.
Hammer S et al.·J Cell Biochem
2008
Structural and functional assessment of TBX20 gene variants in pediatric ventricular septal defect.
Qin Z et al.·Hereditas
2025Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools