TELO2

Chr 16AR

telomere maintenance 2

Also known as: CLK2, TEL2, YHFS

NCBI Gene: 9894ENSG00000100726UniProt: Q9Y4R8

This gene encodes a protein that functions as an S-phase checkpoint protein in the cell cycle. The protein may also play a role in DNA repair.[provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

You-Hoover-Fong syndromeMIM #616954
AR
467
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TELO2
🧬
Gene-Disease Validity (ClinGen)
TELO2-related intellectual disability-neurodevelopmental disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 204 VUS of 467 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.93LOEUF
pLI 0.000
Z-score 1.93
OE 0.67 (0.49–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.37Z-score
OE missense 1.04 (0.97–1.12)
568 obs / 543.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.67 (0.49–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.97–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 27 / 40.2Missense obs/exp: 568 / 543.9Syn Z: -1.95

ClinVar Variant Classifications

467 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic9
VUS204
Likely Benign207
Benign22
Conflicting11
14
Pathogenic
9
Likely Pathogenic
204
VUS
207
Likely Benign
22
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
8
0
14
Likely Pathogenic
6
2
1
0
9
VUS
1
182
19
2
204
Likely Benign
0
14
76
117
207
Benign
0
3
12
7
22
Conflicting
—11
Total12202116126467

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

View in ClinVar →

Protein Context — Lollipop Plot

TELO2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TELO2-related syndromic intellectual disability disorder

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

You-Hoover-Fong syndrome

MIM #616954

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly.
Serey-Gaut M et al.·Am J Hum Genet
2023
TELO2-related syndrome (You-Hoover-Fong syndrome): Description of 14 new affected individuals and review of the literature.
Albokhari D et al.·Am J Med Genet A
2023Review
Milder presentation of TELO2-related syndrome in two sisters homozygous for the p.Arg609His pathogenic variant.
Ciaccio C et al.·Eur J Med Genet
2021Case report
TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2.
Guo Z et al.·Oncol Rep
2021
[Analysis of a child with You-Hoover-Fong syndrome due to compound heterozygous variants of the TELO2 gene and a literature review].
Li P et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025Review
Expansion of the Phenotype of You-Hoover-Fong Syndrome and Possible Increased Risk of Cancer.
De Falco A et al.·Am J Med Genet A
2025Case report
Cataract in You-Hoover-Fong syndrome: TELO2 deficiency.
Del-Prado-Sánchez C et al.·Ophthalmic Genet
2020Case report
Overexpression of TELO2 decreases survival in human high-grade gliomas.
Feng SW et al.·Oncotarget
2016
The first Iranian patient with You-Hoover-Fong syndrome and a review of the literature on 27 cases: expanding the genotypic and phenotypic spectrum.
Shokrollahi N et al.·Neurol Sci
2024Review
Confirmation that variants in TTI2 are responsible for autosomal recessive intellectual disability.
Ziegler A et al.·Clin Genet
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools