PTTG1IP
Chr 21PTTG1 interacting protein
Also known as: C21orf1, C21orf3, PBF, PTTG1IP1
The protein facilitates nuclear translocation of pituitary tumor-transforming 1 protein (PTTG1) and induces transcriptional activation of basic fibroblast growth factor. Mutations cause autosomal recessive pituitary hormone deficiency, dwarfism, and cortisol deficiency, affecting the endocrine system. The gene shows tolerance to loss-of-function variants with low constraint metrics.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
143 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 | 0 | 0 | 83 | 0 | 83 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 24 | 16 | 0 | 40 |
Likely Benign | 0 | 1 | 1 | 0 | 2 |
Benign | 0 | 1 | 0 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 0 | 26 | 104 | 0 | 131 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PTTG1IP · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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