TCF7L2

Chr 10

transcription factor 7 like 2

Also known as: TCF-4, TCF4

NCBI Gene: 6934ENSG00000148737UniProt: Q9NQB0

This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtType 2 diabetes mellitus

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels
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.
4
Active trials
189
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.27
LOEUF· LoF intol.
LOF
Mechanism· G2P
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.27LOEUF
pLI 0.995
Z-score 4.73
OE 0.12 (0.06–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.40Z-score
OE missense 0.64 (0.57–0.72)
227 obs / 354.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.12 (0.06–0.27)
0≤0.351.4
Missense OE?0.64 (0.57–0.72)
0≤0.61.4
Synonymous OE?1.21
0≤1.21.6
LoF obs/exp: 4 / 33.5Missense obs/exp: 227 / 354.0Syn Z: -2.11

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TCF7L2 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients