TWSG1

Chr 18

twisted gastrulation BMP signaling modulator 1

Also known as: TSG

TWSG1 encodes a protein that binds transforming growth factor beta and modulates BMP signaling pathways, which are critical for cartilage development and chondrocyte differentiation. Mutations cause autosomal recessive developmental disorders affecting skeletal and immune system development. The gene shows relatively low constraint to loss-of-function variation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
103
P/LP submissions
0%
P/LP missense
1.03
LOEUF
Mechanism
Clinical SummaryTWSG1
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
98 unique Pathogenic / Likely Pathogenic· 31 VUS of 139 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.006
Z-score 1.51
OE 0.49 (0.261.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.95Z-score
OE missense 0.76 (0.650.90)
97 obs / 127.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.261.03)
00.351.4
Missense OE0.76 (0.650.90)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 5 / 10.2Missense obs/exp: 97 / 127.2Syn Z: 0.02

ClinVar Variant Classifications

139 submitted variants in ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic2
VUS31
Likely Benign3
96
Pathogenic
2
Likely Pathogenic
31
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
0
2
0
2
VUS
0
23
8
0
31
Likely Benign
0
0
1
2
3
Benign
0
0
0
0
0
Total0231072132

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

View in ClinVar →

Protein Context — Lollipop Plot

TWSG1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →