TGFB1

Chr 19ARAD

transforming growth factor beta 1

Also known as: CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1, TGFB, TGFbeta

This gene encodes transforming growth factor beta-1, a secreted signaling molecule that regulates cell proliferation, differentiation, and growth through TGF-beta receptors and SMAD transcription factors. Mutations cause Camurati-Engelmann disease (a progressive bone dysplasia), inflammatory bowel disease with immunodeficiency and encephalopathy, and modify cystic fibrosis lung disease severity. The gene exhibits both autosomal dominant and autosomal recessive inheritance patterns depending on the specific condition.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.613 OMIM phenotypes
Clinical SummaryTGFB1
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Gene-Disease Validity (ClinGen)
inflammatory bowel disease, immunodeficiency, and encephalopathy · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — TGFB1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.61LOEUF
pLI 0.037
Z-score 2.80
OE 0.31 (0.170.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.86Z-score
OE missense 0.66 (0.580.75)
154 obs / 234.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.170.61)
00.351.4
Missense OE0.66 (0.580.75)
00.61.4
Synonymous OE0.80
01.21.6
LoF obs/exp: 6 / 19.3Missense obs/exp: 154 / 234.3Syn Z: 1.65
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTGFB1-related Camurati-Engelmann diseaseOTHERAD
DN
0.6066th %ile
GOF
0.4282th %ile
LOF
0.4136th %ile

The Badonyi & Marsh model scores dominant-negative highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation

Literature Evidence

LOFModulation of tumor induction and progression of oncogenic K-ras-positive tumors in the presence of TGF- b1 haploinsufficiencyPMID:17690114

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TGFB1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Cystic Fibrosis-related DiabetesCystic Fibrosis

Metformin for People With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function

RECRUITING
NCT04530383Phase PHASE2University of Kansas Medical CenterStarted 2022-02-14
Metformin Hydrochloride
Coronary Heart Disease

Adipose Tissue and Inflammation in Coronary Heart Disease

ACTIVE NOT RECRUITING
NCT02760914Oslo University HospitalStarted 2016-06
Non-Alcoholic Fatty Liver Disease

Aronia and Non-alcoholic Fatty Liver Disease

NOT YET RECRUITING
NCT06450769Phase NAIstanbul Kent UniversityStarted 2024-06-15
Aronia juiceMediterranean dietLow-fat diet
EBV-positive Nasopharyngeal Carcinoma

TGF-beta Resistant Cytotoxic T-lymphocytes in Treatment of EBV-positive Nasopharyngeal Carcinoma / RESIST-NPC

ACTIVE NOT RECRUITING
NCT02065362Phase PHASE1Baylor College of MedicineStarted 2015-02
DNR.NPC-specific T cellsDNR.NPC-specific T cells + cyclophosphamide + fludarabine
Central Centrifugal Cicatricial AlopeciaFrontal Fibrosing Alopecia

Deucravacitinib in the Treatment of Cicatricial Alopecias

NOT YET RECRUITING
NCT07508488Phase PHASE2Icahn School of Medicine at Mount SinaiStarted 2026-04
Deucravacitinib
Pre-diabetes

Diet Impact on Hepatic Transcriptomics and Lipidomics in Pre-diabetes

ACTIVE NOT RECRUITING
NCT05965973Phase NALaval UniversityStarted 2023-06-09
Low fat dietHigh fat diet
Metastatic MelanomaStage III Cutaneous Melanoma AJCC v7Stage IIIA Cutaneous Melanoma AJCC v7

Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients With Stage III-IV Melanoma

ACTIVE NOT RECRUITING
NCT01955460Phase PHASE1M.D. Anderson Cancer CenterStarted 2014-10-15
AldesleukinCyclophosphamideFludarabine Phosphate
Healthy

Pulmonary Immune Cell-microbiome Interactions in the Healthy Lung

RECRUITING
NCT05846620Hvidovre University HospitalStarted 2023-04-17
Bronchoalveolar lavage
Congenital Heart Disease (CHD)

Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids

NOT YET RECRUITING
NCT06882772Phase PHASE1, PHASE2University of NebraskaStarted 2026-03
2 mL SunButyrate-TGPlacebo4 mL SunButyrate-TG
Emphysema

Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum

RECRUITING
NCT04761393McMaster UniversityStarted 2022-11-29
Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI
Breast Cancer

Higher Per Daily Treatment-Dose Radiation Therapy or Standard Per Daily Treatment Radiation Therapy in Treating Patients With Early-Stage Breast Cancer That Was Removed by Surgery

ACTIVE NOT RECRUITING
NCT01349322Phase PHASE3Radiation Therapy Oncology GroupStarted 2011-05-24
Standard fractionation whole breast irradiationHypofractionated whole breast irradiationConcurrent boost
Acute-On-Chronic Liver FailureAlcoholic HepatitisLiver Cirrhosis, Alcoholic

A-TANGO Phase 2 Study

NOT YET RECRUITING
NCT06890039Phase PHASE2Yaqrit LtdStarted 2025-09-01
PlaceboTAK-242G-CSF (Filgrastim)
Clinical Literature
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