FTSJ1

Chr XXLR

FtsJ RNA 2'-O-methyltransferase 1

Also known as: CDLIV, JM23, MRX44, MRX9, SPB1, TRMT7, XLID9

NCBI Gene: 24140ENSG00000068438UniProt: Q9UET6OMIM: 300499

This highly constrained gene encodes a methyltransferase that modifies specific nucleotides in the anticodon loop of tRNAs, which is essential for accurate protein synthesis. Mutations cause X-linked intellectual developmental disorder, with males affected due to X-linked recessive inheritance. The protein's critical role in cytoplasmic translation and neurogenesis explains the neurodevelopmental phenotype observed in affected individuals.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.201 OMIM phenotype
Clinical Summary— FTSJ1
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Gene-Disease Validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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
84 unique Pathogenic / Likely Pathogenic· 58 VUS of 225 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 0.993
Z-score 3.54
OE 0.00 (0.00–0.20)
Highly constrained

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

Missense Constraint
2.17Z-score
OE missense 0.50 (0.41–0.60)
73 obs / 147.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.20)
0≤0.351.4
Missense OE0.50 (0.41–0.60)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 0 / 14.6Missense obs/exp: 73 / 147.1Syn Z: 0.46
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFTSJ1-related intellectual developmental disorderLOFXLR
DN
0.3296th %ile
GOF
0.3392th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.20

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

225 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic7
VUS58
Likely Benign28
Benign16
Conflicting3
77
Pathogenic
7
Likely Pathogenic
58
VUS
28
Likely Benign
16
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
68
0
77
Likely Pathogenic
2
2
3
0
7
VUS
1
43
12
2
58
Likely Benign
0
6
7
15
28
Benign
0
3
8
5
16
Conflicting
—3
Total11559822189

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

View in ClinVar →

Protein Context — Lollipop Plot

FTSJ1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
FTSJ1-mediated IL1RN mRNA instability promotes inflammation-driven hepatocellular carcinoma.
Jiang S et al.·J Gastrointest Oncol
2026Open Access
Structural insights into tRNA recognition of the human FTSJ1-THADA complex.
Ishiguro K et al.·Commun Biol
2025Open Access
Downregulation of tRNA methyltransferase FTSJ1 by PM2.5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation.
Wang Y et al.·Cell Death Dis
2024Open Access
Triple-Negative Breast Cancer Intrinsic FTSJ1 Favors Tumor Progression and Attenuates CD8+ T Cell Infiltration.
Sun Y et al.·Cancers (Basel)
2024Open Access
Investigating the Inhibition of FTSJ1, a Tryptophan tRNA-Specific 2'-O-Methyltransferase by NV TRIDs, as a Mechanism of Readthrough in Nonsense Mutated CFTR.
Carollo PS et al.·Int J Mol Sci
2023Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients