TGFB2

Chr 1AD

transforming growth factor beta 2

Also known as: CAEND2, G-TSF, LDS4, TGF-beta2

The protein functions as a secreted ligand that binds TGF-beta receptors to activate SMAD transcription factors and regulate gene expression throughout development. Mutations cause Camurati-Engelmann disease 2 (a bone dysplasia) and Loeys-Dietz syndrome 4 (a connective tissue disorder affecting the cardiovascular system, skeleton, and other organs), both inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variation in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.152 OMIM phenotypes
Clinical SummaryTGFB2
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Gene-Disease Validity (ClinGen)
familial thoracic aortic aneurysm and aortic dissection · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 54 VUS of 100 total submissions
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GeneReview available — TGFB2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

opentargets: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 0.999
Z-score 4.16
OE 0.00 (0.000.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.13Z-score
OE missense 0.62 (0.540.71)
153 obs / 247.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.15)
00.351.4
Missense OE0.62 (0.540.71)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 0 / 20.1Missense obs/exp: 153 / 247.3Syn Z: -0.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTGFB2-related Loeys-Dietz syndromeLOFAD
DN
0.3495th %ile
GOF
0.2497th %ile
LOF
0.66top 25%

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

LOFprediction above median · 1 literature citation · 100% of P/LP variants are LoF · LOEUF 0.15

Literature Evidence

LOFLoss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm.PMID:22772368

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

100 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS54
Likely Benign37
Conflicting1
5
Pathogenic
3
Likely Pathogenic
54
VUS
37
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
0
0
5
Likely Pathogenic
3
0
0
0
3
VUS
3
47
2
2
54
Likely Benign
0
1
10
26
37
Benign
0
0
0
0
0
Conflicting
1
Total11481228100

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

View in ClinVar →

Protein Context — Lollipop Plot

TGFB2 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗