TELO2

Chr 16AR

telomere maintenance 2

Also known as: CLK2, TEL2, YHFS

NCBI Gene: 9894 ENSG00000100726 UniProt: Q9Y4R8 OMIM: 611140

TELO2 encodes a protein that regulates the DNA damage response and is required to stabilize phosphatidylinositol 3-kinase-related protein kinases, while also promoting assembly and maintaining activity of mTORC1 and mTORC2 complexes that regulate cell growth and survival. Mutations cause You-Hoover-Fong syndrome, which follows autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive disease mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

You-Hoover-Fong syndromeMIM #616954

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · TELO2-related intellectual disability-neurodevelopmental disorder · AR · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.93

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 1.93

OE 0.67 (0.49–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.37Z-score

OE missense 1.04 (0.97–1.12)

568 obs / 543.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.67 (0.49–0.93)

0≤0.351.4

Missense OE?1.04 (0.97–1.12)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 27 / 40.2Missense obs/exp: 568 / 543.9Syn Z: -1.95

Background carrier burden — how many people carry a rare variant somewhere in TELO2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,259 rare PASS variants

Rare truncating (LoF)

1 in 1,200

183 rare PASS variants

Rare synonymous (reference)

1 in 56

615 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TELO2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 43	1 in 1,400
South Asian	~43k	1 in 30	1 in 640
Remaining (unassigned)	~30k	1 in 29	1 in 1,200
European (Finnish)	~27k	1 in 110	1 in 2,500
Admixed American	~22k	1 in 31	1 in 2,800
African / African American	~21k	1 in 33	1 in 1,400
East Asian	~20k	1 in 35	1 in 340
Ashkenazi Jewish	~13k	1 in 210	1 in 2,600
Middle Eastern	~2,884	1 in 39	≈ 1 in 690

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 20 coding exons well covered in gnomAD exomes and genomes.? see exons ↓