TCF7

Chr 5

transcription factor 7

Also known as: TCF-1

The encoded protein is a transcriptional activator that binds to T-lymphocyte-specific enhancer elements and is necessary for T-cell differentiation and survival of CD4+CD8+ immature thymocytes. Loss-of-function mutations in TCF7 cause autosomal recessive T-cell immunodeficiency with absent or severely reduced T-cells, leading to severe combined immunodeficiency. The pathogenic mechanism involves disrupted T-lymphocyte development due to impaired Wnt/beta-catenin signaling and loss of transcriptional activation of essential T-cell genes.

Summary from RefSeq, UniProt
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1
Active trials
80
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.71
LOEUF
DN
Mechanism· predicted
Clinical SummaryTCF7
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.005
Z-score 2.47
OE 0.38 (0.210.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.51Z-score
OE missense 0.90 (0.791.02)
173 obs / 192.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.210.71)
00.351.4
Missense OE0.90 (0.791.02)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 7 / 18.5Missense obs/exp: 173 / 192.8Syn Z: -1.77
DN
0.6455th %ile
GOF
0.5071th %ile
LOF
0.52top 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TCF7 · protein map & ClinVar variants

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

Clinical Literature
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