TMEM53
Chr 1ARtransmembrane protein 53
Also known as: CTDI, NET4
TMEM53 encodes a nuclear membrane protein that regulates bone formation by blocking the nuclear translocation of phosphorylated SMAD1/5/9 proteins, thereby inhibiting BMP signaling in osteoblast cells. Biallelic mutations cause craniotubular dysplasia, Ikegawa type, an autosomal recessive skeletal dysplasia. The gene shows tolerance to loss-of-function variation in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
66 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 5 | 0 | 6 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 45 | 8 | 0 | 53 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 1 | 48 | 15 | 1 | 65 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM53 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools