TEAD4

Chr 12

TEA domain transcription factor 4

Also known as: EFTR-2, RTEF1, TCF13L1, TEF-3, TEF3, TEFR-1, hRTEF-1B

TEAD4 encodes a transcription factor that binds to regulatory elements in muscle-specific gene promoters and mediates gene expression in the Hippo signaling pathway, which controls cell proliferation and organ size. Mutations cause Sveinsson chorioretinal atrophy, an autosomal dominant progressive retinal degeneration typically presenting in adulthood with night blindness and visual field defects. The gene shows low constraint against loss-of-function variants, suggesting some tolerance to reduced function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
93
Pubs (1 yr)
63
P/LP submissions
0%
P/LP missense
0.81
LOEUF
DN
Mechanism· predicted
Clinical SummaryTEAD4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 70 VUS of 152 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.24
OE 0.49 (0.310.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.38Z-score
OE missense 0.77 (0.690.86)
216 obs / 281.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.310.81)
00.351.4
Missense OE0.77 (0.690.86)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 11 / 22.4Missense obs/exp: 216 / 281.4Syn Z: -0.23
DN
0.6260th %ile
GOF
0.5072th %ile
LOF
0.50top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

152 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic3
VUS70
Likely Benign5
60
Pathogenic
3
Likely Pathogenic
70
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
3
0
3
VUS
0
62
8
0
70
Likely Benign
0
1
2
2
5
Benign
0
0
0
0
0
Total063732138

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

View in ClinVar →

Protein Context — Lollipop Plot

TEAD4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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