TSC22D1

Chr 13

TSC22 domain family member 1

Also known as: HUCEP-2, Ptg-2, TGFB1I4, TSC22

NCBI Gene: 8848ENSG00000102804UniProt: Q15714OMIM: 607715

This gene encodes a leucine zipper transcription factor that represses transcription of multiple genes including C-type natriuretic peptide and regulates TGF-beta signaling pathways involved in apoptosis and tumor suppression. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.33), but no established Mendelian disease associations have been reported in the provided data. A promoter polymorphism has been associated with diabetic nephropathy susceptibility.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.33
Clinical Summary— TSC22D1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
51 unique Pathogenic / Likely Pathogenic· 20 VUS of 82 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.960
Z-score 4.43
OE 0.16 (0.08–0.33)
Highly constrained

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

Missense Constraint
-0.88Z-score
OE missense 1.10 (1.03–1.18)
621 obs / 562.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.16 (0.08–0.33)
0≤0.351.4
Missense OE1.10 (1.03–1.18)
0≤0.61.4
Synonymous OE1.28
0≤1.21.6
LoF obs/exp: 5 / 32.1Missense obs/exp: 621 / 562.2Syn Z: -3.28
DN
0.2798th %ile
GOF
0.3292th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.33

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

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
VUS20
Likely Benign3
Benign2
51
Pathogenic
20
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
51
0
51
Likely Pathogenic
0
0
0
0
0
VUS
1
18
1
0
20
Likely Benign
0
2
0
1
3
Benign
0
0
0
2
2
Total12052376

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

View in ClinVar →

Protein Context — Lollipop Plot

TSC22D1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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