TTI1

Chr 20AR

TELO2 interacting protein 1

Also known as: KIAA0406, NEDMIM, smg-10

TTI1 encodes a regulator of the DNA damage response and stabilizes phosphatidylinositol 3-kinase-related protein kinases, while also promoting assembly and maintaining activity of mTORC1 and mTORC2 complexes that regulate cell growth and survival. Autosomal recessive mutations cause neurodevelopmental disorder with microcephaly and movement abnormalities. The gene shows low constraint to loss-of-function variation, consistent with its recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly and movement abnormalitiesMIM #620445
AR
0
Active trials
3
Pubs (1 yr)
9
P/LP submissions
67%
P/LP missense
0.82
LOEUF
DN
Mechanism· predicted
Clinical SummaryTTI1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 162 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.000
Z-score 2.42
OE 0.57 (0.400.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.22Z-score
OE missense 0.97 (0.911.04)
545 obs / 559.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.400.82)
00.351.4
Missense OE0.97 (0.911.04)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 21 / 36.9Missense obs/exp: 545 / 559.6Syn Z: -0.72
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateTTI1-related microcephaly, intellectual disability and ataxiaOTHERAR

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

DN
0.6356th %ile
GOF
0.5660th %ile
LOF
0.2874th %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

200 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic4
VUS162
Likely Benign17
5
Pathogenic
4
Likely Pathogenic
162
VUS
17
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
1
0
5
Likely Pathogenic
0
4
0
0
4
VUS
3
154
5
0
162
Likely Benign
0
6
0
11
17
Benign
0
0
0
0
0
Total5166611188

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

View in ClinVar →

Protein Context — Lollipop Plot

TTI1 · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC