TINF2
Chr 14ADTERF1 interacting nuclear factor 2
Also known as: DKCA3, DKCA5, TIN2
The protein is a critical component of the shelterin complex that protects telomeres from being recognized as DNA breaks and regulates telomere length. Mutations cause dyskeratosis congenita and Revesz syndrome, inherited bone marrow failure syndromes that affect multiple organ systems including skin, nails, and hematopoietic system. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function 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.
Literature Evidence
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
200 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 | 3 | 1 | 2 | 0 | 6 |
Likely Pathogenic | 1 | 2 | 0 | 0 | 3 |
VUS | 17 | 98 | 8 | 1 | 124 |
Likely Benign | 0 | 0 | 25 | 36 | 61 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 4 | |||
| Total | 21 | 101 | 37 | 37 | 200 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TINF2 · 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