TTI2

Chr 8AR

TELO2 interacting protein 2

Also known as: C8orf41, MRT39

NCBI Gene: 80185ENSG00000129696UniProt: Q6NXR4OMIM: 614426

The protein regulates the DNA damage response as part of the TTT complex, which stabilizes phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins and promotes cellular resistance to DNA damage stresses including ionizing radiation and UV exposure. Biallelic mutations cause autosomal recessive intellectual developmental disorder. This gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.041 OMIM phenotype
Clinical Summary— TTI2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
72 unique Pathogenic / Likely Pathogenic· 83 VUS of 217 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.41
OE 0.66 (0.43–1.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.29Z-score
OE missense 1.05 (0.95–1.16)
284 obs / 270.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.43–1.04)
0≤0.351.4
Missense OE1.05 (0.95–1.16)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 13 / 19.8Missense obs/exp: 284 / 270.6Syn Z: -0.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTTI2-related intellectual developmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6551th %ile
GOF
0.6150th %ile
LOF
0.2776th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

217 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic67
Likely Pathogenic5
VUS83
Likely Benign35
Benign6
Conflicting7
67
Pathogenic
5
Likely Pathogenic
83
VUS
35
Likely Benign
6
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
4
61
0
67
Likely Pathogenic
2
1
2
0
5
VUS
6
72
5
0
83
Likely Benign
0
12
2
21
35
Benign
1
2
1
2
6
Conflicting
—7
Total11917123203

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

View in ClinVar →

Protein Context — Lollipop Plot

TTI2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients