TGFB1I1

Chr 16

transforming growth factor beta 1 induced transcript 1

Also known as: ARA55, HIC-5, HIC5, TSC-5

NCBI Gene: 7041ENSG00000140682UniProt: O43294

This gene encodes a coactivator of the androgen receptor, a transcription factor which is activated by androgen and has a key role in male sexual differentiation. The encoded protein is thought to regulate androgen receptor activity and may have a role to play in the treatment of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

90
ClinVar variants
8
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— TGFB1I1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 71 VUS of 90 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.027
Z-score 3.07
OE 0.31 (0.17–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.55Z-score
OE missense 0.75 (0.67–0.84)
225 obs / 300.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.17–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.67–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 7 / 22.8Missense obs/exp: 225 / 300.7Syn Z: 1.21

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS71
Likely Benign1
7
Pathogenic
1
Likely Pathogenic
71
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
65
6
0
71
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total06614080

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

View in ClinVar →

Protein Context — Lollipop Plot

TGFB1I1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Endothelin-1 (ET-1) contributes to senescence and phenotypic changes in brain pericytes in diabetes-mimicking conditions.
Edgerton-Fulton M et al.·Clin Sci (Lond)
2024
Transforming growth factor-β1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein.
Wang X et al.·J Biol Chem
2011
Could perturbed fetal development of the ovary contribute to the development of polycystic ovary syndrome in later life?
Hartanti MD et al.·PLoS One
2020
Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy.
Small GW et al.·Cells
2023
Biomarkers of Periodontitis and Its Differential DNA Methylation and Gene Expression in Immune Cells: A Systematic Review.
Cárdenas AM et al.·Int J Mol Sci
2022Review
Hic-5 is required for myofibroblast differentiation by regulating mechanically dependent MRTF-A nuclear accumulation.
Varney SD et al.·J Cell Sci
2016
Network-based identification of key master regulators associated with an immune-silent cancer phenotype.
Mall R et al.·Brief Bioinform
2021
MicroRNA MiR-199a-5p regulates smooth muscle cell proliferation and morphology by targeting WNT2 signaling pathway.
Hashemi Gheinani A et al.·J Biol Chem
2015
Construction and experimental validation of a macrophage cell senescence-related gene signature to evaluate the prognosis, immunotherapeutic sensitivity, and chemotherapy response in bladder cancer.
Jiang Q et al.·Funct Integr Genomics
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring.
Wu L et al.·Ecotoxicol Environ Saf
2024
TGFB1I1 promotes cell proliferation and migration in urothelial carcinoma.
Liang PI et al.·Kaohsiung J Med Sci
2024🔓 Open Access
PTHR1 May Be Involved in Progression of Osteosarcoma by Regulating miR-124-3p-AR-Tgfb1i1, miR-27a-3p-PPARG-Abca1, and miR-103/590-3p-AXIN2 Axes.
Li S et al.·DNA Cell Biol
2019
Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas.
Liu Y et al.·Oncotarget
2014🔓 Open Access
Identification of Nkx2-3 and TGFB1I1 expression levels as potential biomarkers to predict the effects of FOLFOX4 chemotherapy.
Li S et al.·Cancer Biol Ther
2012
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools