TNRC18

Chr 7

trinucleotide repeat containing 18

Also known as: CAGL79, TNRC18A

TNRC18 encodes a chromatin reader protein that binds trimethylated histone H3K9 and recruits corepressor complexes to silence endogenous retroviruses. The gene is highly constrained against loss-of-function variants (pLI = 0.99, LOEUF = 0.29), but no definitive human disease associations have been established to date. Further research is needed to determine if TNRC18 variants cause neurodevelopmental disorders in humans.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.29
Clinical SummaryTNRC18
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.991
Z-score 6.91
OE 0.19 (0.130.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
-0.26Z-score
OE missense 1.02 (0.981.06)
1647 obs / 1617.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.19 (0.130.29)
00.351.4
Missense OE1.02 (0.981.06)
00.61.4
Synonymous OE1.33
01.21.6
LoF obs/exp: 16 / 84.6Missense obs/exp: 1647 / 1617.3Syn Z: -7.12
DN
0.19100th %ile
GOF
0.2198th %ile
LOF
0.89top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TNRC18 · 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

No active trials found for this gene.

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Clinical Literature
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