TCF20

Chr 22AD

transcription factor 20

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

NCBI Gene: 6942 ENSG00000100207 UniProt: Q9UGU0 OMIM: 603107

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a transcription factor that recognizes the platelet-derived growth factor-responsive element in the matrix metalloproteinase 3 promoter. The encoded protein is thought to be a transcriptional coactivator, enhancing the activity of transcription factors such as JUN and SP1. Mutations in this gene are associated with autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.101 OMIM phenotype

Clinical Summary— TCF20

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Gene-Disease Validity (ClinGen)

developmental delay with variable intellectual impairment and behavioral abnormalities · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 7.32

OE 0.03 (0.01–0.10)

Highly constrained

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

Missense Constraint?

0.09Z-score

OE missense 0.99 (0.94–1.04)

1048 obs / 1056.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.10)

0≤0.351.4

Missense OE?0.99 (0.94–1.04)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

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

This gene — mechanism propensity

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 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFDe novo nonsense and frameshift variants of TCF20 in individuals with intellectual disability and postnatal overgrowth1

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

References