TNRC18

Chr 7

trinucleotide repeat containing 18

Also known as: CAGL79, TNRC18A

NCBI Gene: 84629 ENSG00000182095 UniProt: O15417

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.

ResearchSummary from RefSeq, UniProt

Predicted to enable chromatin binding activity. Located in cytosol; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.29

Clinical Summary— TNRC18

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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.

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ClinVar Variants

712 VUS of 963 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.991

Z-score 6.91

OE 0.19 (0.13–0.29)

Highly constrained

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

Missense Constraint?

-0.26Z-score

OE missense 1.02 (0.98–1.06)

1647 obs / 1617.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.19 (0.13–0.29)

0≤0.351.4

Missense OE?1.02 (0.98–1.06)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 16 / 84.6Missense obs/exp: 1647 / 1617.3Syn Z: -7.12

This gene — mechanism propensity

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

963 submitted variants in ClinVar

ClinVar

Classification Summary

VUS712

Likely Benign75

Benign113

Conflicting9

712

VUS

Likely Benign

113

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	708	2	0	712
Likely Benign	0	21	3	51	75
Benign	0	18	59	36	113
Conflicting	—				9
Total	2	747	64	87	909

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

View in ClinVar →

49 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap TNRC18 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →