TCF20

Chr 22AD

transcription factor 20

Also known as: AR1, DDVIBA, SPBP, TCF-20

TCF20 encodes a transcriptional coactivator that recognizes the platelet-derived growth factor-responsive element in the matrix metalloproteinase 3 promoter and enhances the activity of transcription factors including JUN and SP1. Loss-of-function mutations cause autosomal dominant developmental delay with variable intellectual impairment and behavioral abnormalities, including autism spectrum disorders. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the underlying disease mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical SummaryTCF20
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Gene-Disease Validity (ClinGen)
developmental delay with variable intellectual impairment and behavioral abnormalities · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 7.32
OE 0.03 (0.010.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
0.09Z-score
OE missense 0.99 (0.941.04)
1048 obs / 1056.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.010.10)
00.351.4
Missense OE0.99 (0.941.04)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 2 / 66.4Missense obs/exp: 1048 / 1056.2Syn Z: -3.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTCF20-related developmental delay with variable intellectual impairment and behavioural abnormalitiesLOFAD
DN
0.17100th %ile
GOF
0.09100th %ile
LOF
0.91top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.10

Literature Evidence

LOFDe novo nonsense and frameshift variants of TCF20 in individuals with intellectual disability and postnatal overgrowthPMID:27436265

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TCF20 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC