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…

Primary Disease Associations & Inheritance

Developmental delay with variable intellectual impairment and behavioral abnormalitiesMIM #618430

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · developmental delay with variable intellectual impairment and behavioral abnormalities · AD · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in TCF20?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

2,529 rare PASS variants

Rare truncating (LoF)

1 in 8,200

33 rare PASS variants

Rare synonymous (reference)

1 in 35

1,121 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TCF20. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 38	1 in 18,000
South Asian	~43k	1 in 28	1 in 1,600
Remaining (unassigned)	~30k	1 in 26	≈ 1 in 15,000
European (Finnish)	~27k	1 in 130	1 in 3,300
Admixed American	~22k	1 in 29	none seen
African / African American	~21k	1 in 29	≈ 1 in 6,900
East Asian	~20k	1 in 29	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 80	none seen
Middle Eastern	~2,884	1 in 25	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.