FTSJ1

Summary

FTSJ1 (FtsJ RNA 2’-O-methyltransferase 1, HGNC:13254) is a protein-coding gene on chromosome Xp11.23, encoding tRNA (cytidine(32)/guanosine(34)-2’-O)-methyltransferase (Q9UET6). Methylates the 2’-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs.

This gene encodes a member of the methyltransferase superfamily. The encoded protein localizes to the nucleolus, binds to S-adenosylmethionine, and may be involved in the processing and modification of ribosomal RNA. Mutations in this gene are associated with cognitive disability. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 24140 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 154 total — 10 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 19
• Dosage sensitivity (ClinGen): haploinsufficiency emerging evidence, triplosensitivity no evidence
• MANE Select transcript: NM_012280

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13254
Approved symbol	FTSJ1
Name	FtsJ RNA 2’-O-methyltransferase 1
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	JM23, CDLIV, SPB1, TRM7, TRMT7
Ensembl gene	ENSG00000068438
Ensembl biotype	protein_coding
OMIM	300499
Entrez	24140

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 22 protein_coding, 10 protein_coding_CDS_not_defined

ENST00000019019, ENST00000348411, ENST00000396894, ENST00000466371, ENST00000467954, ENST00000473235, ENST00000475806, ENST00000485486, ENST00000487353, ENST00000489599, ENST00000490202, ENST00000492562, ENST00000496365, ENST00000898808, ENST00000898809, ENST00000898810, ENST00000898811, ENST00000898812, ENST00000898813, ENST00000898814, ENST00000898815, ENST00000898816, ENST00000898817, ENST00000918484, ENST00000918485, ENST00000918486, ENST00000951061, ENST00000951062, ENST00000951063, ENST00000951064, ENST00000951065, ENST00000951066

RefSeq mRNA: 3 — MANE Select: NM_012280 NM_001282157, NM_012280, NM_177439

CCDS: CCDS14294, CCDS14295, CCDS75972

Canonical transcript exons

ENST00000348411 — 13 exons

Exon	Start	End
ENSE00000867072	48477961	48478168
ENSE00001924841	48485736	48486350
ENSE00003529098	48482403	48482506
ENSE00003529618	48481289	48481342
ENSE00003591150	48481632	48481715
ENSE00003592278	48478617	48478707
ENSE00003644621	48481151	48481203
ENSE00003647056	48482597	48482794
ENSE00003652951	48482986	48483027
ENSE00003672751	48479038	48479116
ENSE00003682019	48481426	48481528
ENSE00003691451	48478449	48478518
ENSE00003847908	48476199	48476396

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 93.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.0658 / max 131.7775, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196239	31.1265	1813
196242	1.5087	890
196243	0.5308	293
196241	0.5166	302
196240	0.3832	203

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	93.03	gold quality
granulocyte	CL:0000094	92.61	gold quality
cortical plate	UBERON:0005343	92.38	gold quality
body of pancreas	UBERON:0001150	91.87	gold quality
ganglionic eminence	UBERON:0004023	91.63	gold quality
left uterine tube	UBERON:0001303	91.39	gold quality
cerebellar hemisphere	UBERON:0002245	91.13	gold quality
cerebellar cortex	UBERON:0002129	91.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.00	gold quality
right lobe of thyroid gland	UBERON:0001119	90.75	gold quality
ascending aorta	UBERON:0001496	90.75	gold quality
thoracic aorta	UBERON:0001515	90.72	gold quality
left adrenal gland cortex	UBERON:0035825	90.71	gold quality
right ovary	UBERON:0002118	90.67	gold quality
endocervix	UBERON:0000458	90.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.64	gold quality
left adrenal gland	UBERON:0001234	90.58	gold quality
periodontal ligament	UBERON:0008266	90.50	gold quality
ectocervix	UBERON:0012249	90.48	gold quality
left ovary	UBERON:0002119	90.44	gold quality
adenohypophysis	UBERON:0002196	90.41	gold quality
right adrenal gland	UBERON:0001233	90.40	gold quality
left coronary artery	UBERON:0001626	90.34	gold quality
upper lobe of left lung	UBERON:0008952	90.32	gold quality
left lobe of thyroid gland	UBERON:0001120	90.31	gold quality
minor salivary gland	UBERON:0001830	90.28	gold quality
right coronary artery	UBERON:0001625	90.21	gold quality
cerebellum	UBERON:0002037	90.20	gold quality
adrenal cortex	UBERON:0001235	90.08	gold quality
nasal cavity mucosa	UBERON:0001826	90.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting FTSJ1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-3145-3P	98.85	69.07	2031

Functional genomics

ClinGen dosage: haploinsufficiency 2 (emerging evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• Spb1p is a homologous yeast nucleolar protein (PMID:10648622)
• May play a role in the regulation of translation. Mutations cause X-linked mental retardation. (PMID:15162322)
• A splice site mutation is associated with non-syndromic mental retardation in a large Belgian family (PMID:15342698)
• A 50kb deletion at Xp11.23 including the two genes, SLC38A5 and FTSJ1 was found in 3 brothers with moderate to severe mental retardation. (PMID:17333282)
• identified a novel FTSJ1 mutation in an X-linked mental retardation family through mutation screening of a cohort of 73 unrelated Japanese male probands with MR (PMID:18081026)
• Results suggest a positive association between genetic variants and nonsyndromic X-linked mental retardation in young male subjects in the Chinese Han population. (PMID:18401546)
• These findings suggest that genetic variations in FtsJ homolog 1 (E. coli) possibly influence human cognitive ability. (PMID:19012053)
• we have provided strong evidence that human FTSJ1 is required for Cm32 and Gm34 modification of tRNAPhe. (PMID:26310293)
• Mutations in the Ftsj1 gene is associated with intellectual disability. (PMID:30557699)
• FTSJ1 regulates tRNA 2’-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression. (PMID:32393790)
• Intellectual disability-associated gene ftsj1 is responsible for 2’-O-methylation of specific tRNAs. (PMID:32558197)
• The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance. (PMID:36720500)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ftsj1	ENSDARG00000057089
mus_musculus	Ftsj1	ENSMUSG00000031171
rattus_norvegicus	Ftsj1	ENSRNOG00000004776
drosophila_melanogaster	Trm7-32	FBGN0038471
drosophila_melanogaster	Trm7-34	FBGN0038861
caenorhabditis_elegans		WBGENE00011281

Paralogs (2): FTSJ3 (ENSG00000108592), MRM2 (ENSG00000122687)

Protein

Protein identifiers

tRNA (cytidine(32)/guanosine(34)-2’-O)-methyltransferase — Q9UET6 (reviewed: Q9UET6)

Alternative names: 2’-O-ribose RNA methyltransferase TRM7 homolog, Protein ftsJ homolog 1

All UniProt accessions (3): Q9UET6, A0A024QYX5, B7Z4K4

UniProt curated annotations — full annotation on UniProt →

Function. Methylates the 2’-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs. Requisite for faithful cytoplasmic translation. Requires THADA for methylation of the nucleotide at position 32 of the anticodon loop of substrate tRNAs. Requires WDR6 for methylation of the nucleotide at position 34 of the anticodon loop of substrate tRNAs. Promotes translation efficiency of the UUU codon. Plays a role in neurogenesis. Required for expression of genes involved in neurogenesis, mitochondrial translation and energy generation, and lipid biosynthesis. Requisite for RNA-mediated gene silencing. May modify position 32 in tRNA(Arg(ACG)), tRNA(Arg(CCG)), tRNA(Arg(UCG)), tRNA(Cys(GCA)), tRNA(Cys(ACA)), tRNA(Gln(CUG)), tRNA(Gln(UUG)), tRNA(Gly(CCC)), tRNA(Leu(CAG))/tRNA(Leu(CAA)), tRNA(Leu(A/IAG)), tRNA(Leu(UAG)), tRNA(Phe(GAA)), tRNA(Pro(AGG))/tRNA(Pro(CGG))/tRNA(Pro(UGG)) and tRNA(Trp(CCA)), and position 34 in tRNA(Phe(GAA)), tRNA(Leu(CAA)), tRNA(Sec(UCA)), and tRNA(Trp(CCA)).

Subunit / interactions. Interacts with WDR6; the interaction is direct, and required for 2’-O-methylation of position 34 in substrate tRNAs.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Found in fetal brain, lung, liver and kidney. Widely expressed in adult tissue; with high expression in heart and liver, lower expression in skeletal muscle, kidney, and pancreas and also lowly expressed in brain and lung. In the adult brain, expressed in amygdala, caudate nucleus, corpus callosum, hippocampus and thalamus.

Disease relevance. Intellectual developmental disorder, X-linked 9 (XLID9) [MIM:309549] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by 2,6-diaminopurine (DAP); inhibition promotes UGA stop-codon readthrough during translation by misincorporation of tRNA(Trp) in the nascent polypeptide.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. TRM7 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UET6-1	1	yes
Q9UET6-2	2

RefSeq proteins (3): NP_001269086, NP_036412, NP_803188 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002877	RNA_MeTrfase_FtsJ_dom	Domain
IPR015507	rRNA-MeTfrase_E	Family
IPR028590	RNA_methyltr_E_TRM7	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR050082	RNA_methyltr_RlmE	Family

Pfam: PF01728

Catalyzed reactions (Rhea), 1 shown:

• cytidine(32)/guanosine(34) in tRNA + 2 S-adenosyl-L-methionine = 2’-O-methylcytidine(32)/2’-O-methylguanosine(34) in tRNA + 2 S-adenosyl-L-homocysteine + 2 H(+) (RHEA:42396)

UniProt features (11 total): binding site 5, chain 1, region of interest 1, sequence variant 1, active site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8Y2O	ELECTRON MICROSCOPY	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UET6-F1	84.91	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 156 (proton acceptor)

Ligand- & substrate-binding residues (5): 53; 55; 75; 91; 116

Post-translational modifications (1): 271

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol

MSigDB gene sets: 169 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_CYTOPLASMIC_TRANSLATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_TRNA_METABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEUROGENESIS, GOBP_RNA_METHYLATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_RNA_MODIFICATION, GOBP_TRNA_METHYLATION, DOUGLAS_BMI1_TARGETS_UP, DANG_BOUND_BY_MYC, GOBP_METHYLATION

GO Biological Process (9): tRNA nucleoside ribose methylation (GO:0002128), wobble position ribose methylation (GO:0002130), cytoplasmic translation (GO:0002181), tRNA modification (GO:0006400), neurogenesis (GO:0022008), tRNA methylation (GO:0030488), RNA methylation (GO:0001510), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (8): tRNA methyltransferase activity (GO:0008175), tRNA (guanine) methyltransferase activity (GO:0016423), obsolete tRNA 2’-O-methyltransferase activity (GO:0106050), tRNA (guanosine(34)-2’-O-ribose)-methyltransferase activity (GO:0106340), S-adenosyl-L-methionine binding (GO:1904047), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA modification	2
cellular anatomical structure	2
tRNA methylation	1
tRNA nucleoside ribose methylation	1
translation	1
tRNA processing	1
nervous system development	1
cell differentiation	1
RNA methylation	1
tRNA modification	1
macromolecule methylation	1
RNA processing	1
tRNA metabolic process	1
metabolic process	1
RNA methyltransferase activity	1
catalytic activity, acting on a tRNA	1
tRNA methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
tRNA (guanine) methyltransferase activity	1
cation binding	1
sulfur compound binding	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FTSJ1	SLC38A5	Q8WUX1	860
FTSJ1	ZNF41	P51814	843
FTSJ1	PQBP1	O60828	831
FTSJ1	NSUN2	Q08J23	760
FTSJ1	WDR4	P57081	744
FTSJ1	TRMT5	Q32P41	733
FTSJ1	TRMT1	Q9NXH9	725
FTSJ1	TRMT11	Q7Z4G4	717
FTSJ1	ADAT3	Q96EY9	716
FTSJ1	TRMT61A	Q96FX7	710
FTSJ1	TRMT10A	Q8TBZ6	708
FTSJ1	TARBP1	Q13395	704
FTSJ1	TRMT6	Q9UJA5	691
FTSJ1	PUS3	Q9BZE2	690
FTSJ1	WDR6	Q9NNW5	681

IntAct

156 interactions, top by confidence:

A	B	Type	Score
CDC37	IKBKB	psi-mi:“MI:0914”(association)	0.850
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CERT1	FTSJ1	psi-mi:“MI:0915”(physical association)	0.560
FTSJ1	CERT1	psi-mi:“MI:0915”(physical association)	0.560
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
FTSJ1	WDR6	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
Cdc37	STX18	psi-mi:“MI:0914”(association)	0.350
FTSJ1		psi-mi:“MI:0914”(association)	0.350
USP43	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ORF28	PEX19	psi-mi:“MI:0914”(association)	0.350
SUN2		psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
incE	STX7	psi-mi:“MI:0914”(association)	0.350
DMWD	P4HA2	psi-mi:“MI:0914”(association)	0.350
PIK3R1	PIK3R2	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLK2	PRPF4	psi-mi:“MI:0914”(association)	0.350
ERBB2	ILVBL	psi-mi:“MI:0914”(association)	0.350
NTRK1	ILVBL	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CX3CL1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
WDR5B	HSPA8	psi-mi:“MI:0914”(association)	0.350
ELAC2	TOMM40	psi-mi:“MI:0914”(association)	0.350
SLC1A6	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC22A2	RAB27B	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): WDR6 (Co-fractionation), FTSJ1 (Proximity Label-MS), DYSF (Affinity Capture-MS), CDC37 (Affinity Capture-MS), WDR6 (Affinity Capture-MS), FTSJ1 (Affinity Capture-MS), FTSJ1 (Affinity Capture-MS), IBTK (Affinity Capture-MS), SIRT6 (Affinity Capture-MS), GNL3L (Affinity Capture-MS), MRM1 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), RPS19BP1 (Affinity Capture-MS), FTSJ1 (Affinity Capture-MS), FTSJ1 (Affinity Capture-MS)

ESM2 similar proteins: A1CX75, A6S8E7, A6SRX6, A8NWP2, B0Y5C3, B0Y691, B4H4I3, B4JLU7, B4L529, B4M703, B4N278, B9JSD2, C7YK87, C8VJ35, F5HAU9, O36015, O59954, O74468, P00908, P05328, P06531, P25170, P25627, P36858, P38238, P53200, P54886, Q09833, Q22031, Q28H76, Q29I16, Q2U696, Q2UH11, Q4PEJ3, Q4WNI1, Q4WPE6, Q4WX30, Q54VA8, Q5H737, Q5R4M8

Diamond homologs: A0B8A1, A1TQF0, A1TXM4, A1URN3, A1W8H0, A4XYE8, A5VFI9, A5VUZ8, A5WCU8, A6U6F0, A6VCK9, A6X5L4, A7IDJ5, A8EXN1, A8GMD3, A8GV60, A8II77, A9IMA1, A9MBW8, A9WYY2, B2SAY0, B3PLQ4, B3PQL4, B5ZR94, B7V1G4, B9J9U0, B9JSD2, B9LSX2, C0RLJ5, C1DFL6, C3K267, C3MGQ4, C5CKU4, O27801, O28228, O36015, O42832, P0CS78, P0CS79, P25582

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ERBB2 ECD mutants	6	30.3×	3e-07
Constitutive Signaling by EGFRvIII	5	26.8×	9e-06
Antigen processing: Ub, ATP-independent proteasomal degradation	6	25.8×	1e-06
Regulation of activated PAK-2p34 by proteasome mediated degradation	11	23.0×	8e-11
Tie2 Signaling	5	22.6×	2e-05
Regulation of ornithine decarboxylase (ODC)	11	22.5×	9e-11
AUF1 (hnRNP D0) binds and destabilizes mRNA	12	22.4×	4e-11
Vpu mediated degradation of CD4	11	22.0×	9e-11

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	6	15.9×	2e-03
ephrin receptor signaling pathway	6	13.0×	4e-03
cell surface receptor protein tyrosine kinase signaling pathway	7	7.7×	7e-03
positive regulation of neuron projection development	8	6.9×	6e-03
protein folding	9	5.8×	6e-03
protein stabilization	11	4.6×	6e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	12	3.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

154 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	5
Uncertain significance	53
Likely benign	26
Benign	17

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
10894	NM_012280.4(FTSJ1):c.655G>A (p.Asp219Asn)	Pathogenic
10895	NM_012280.4(FTSJ1):c.196C>T (p.Gln66Ter)	Pathogenic
10896	NM_012280.4(FTSJ1):c.121+1del	Pathogenic
10897	NM_012280.4(FTSJ1):c.192-2A>G	Pathogenic
1183994	NM_012280.4(FTSJ1):c.61_64del (p.Trp21fs)	Pathogenic
1732349	NM_012280.4(FTSJ1):c.352del (p.Ala118fs)	Pathogenic
208659	NM_012280.4(FTSJ1):c.34T>A (p.Tyr12Asn)	Pathogenic
2317952	NM_012280.4(FTSJ1):c.133del (p.Ala45fs)	Pathogenic
975240	NM_012280.4(FTSJ1):c.256del (p.Val86fs)	Pathogenic
981372	NM_012280.4(FTSJ1):c.362-2A>T	Pathogenic
3897579	NM_012280.4(FTSJ1):c.587G>A (p.Cys196Tyr)	Likely pathogenic
3900670	NM_012280.4(FTSJ1):c.-88+644_-88+645del	Likely pathogenic
4293311	NM_012280.4(FTSJ1):c.759+1G>A	Likely pathogenic
520557	NM_012280.4(FTSJ1):c.161G>C (p.Ser54Thr)	Likely pathogenic
624409	NM_012280.4(FTSJ1):c.877dup (p.Gln293fs)	Likely pathogenic

SpliceAI

1794 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48478144:GA:G	donor_gain	1.0000
X:48478145:A:G	donor_gain	1.0000
X:48478150:G:GT	donor_gain	1.0000
X:48478151:A:T	donor_gain	1.0000
X:48478438:T:G	acceptor_gain	1.0000
X:48478442:T:G	acceptor_gain	1.0000
X:48478448:GGC:G	acceptor_gain	1.0000
X:48478613:ACAG:A	acceptor_gain	1.0000
X:48478614:CA:C	acceptor_loss	1.0000
X:48478615:A:AG	acceptor_gain	1.0000
X:48478615:AG:A	acceptor_gain	1.0000
X:48478615:AGG:A	acceptor_gain	1.0000
X:48478615:AGGG:A	acceptor_gain	1.0000
X:48478616:G:GT	acceptor_gain	1.0000
X:48478616:GG:G	acceptor_gain	1.0000
X:48478616:GGG:G	acceptor_gain	1.0000
X:48478616:GGGG:G	acceptor_gain	1.0000
X:48478616:GGGGC:G	acceptor_gain	1.0000
X:48478704:CCAG:C	donor_loss	1.0000
X:48478705:CAG:C	donor_loss	1.0000
X:48478709:T:A	donor_loss	1.0000
X:48481145:CCACA:C	acceptor_loss	1.0000
X:48481146:CACA:C	acceptor_loss	1.0000
X:48481147:ACAGT:A	acceptor_loss	1.0000
X:48481148:CA:C	acceptor_loss	1.0000
X:48481149:A:AC	acceptor_loss	1.0000
X:48481149:A:AG	acceptor_gain	1.0000
X:48481150:G:GA	acceptor_gain	1.0000
X:48481150:GT:G	acceptor_gain	1.0000
X:48481150:GTA:G	acceptor_gain	1.0000

AlphaMissense

2145 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48478131:A:C	K28N	0.999
X:48478131:A:T	K28N	0.999
X:48478490:T:A	W55R	0.999
X:48478490:T:C	W55R	0.999
X:48479102:A:T	D116V	0.999
X:48481634:G:C	A192P	0.999
X:48481637:T:C	F193L	0.999
X:48481639:C:A	F193L	0.999
X:48481639:C:G	F193L	0.999
X:48478075:G:C	D10H	0.998
X:48478098:G:C	K17N	0.998
X:48478098:G:T	K17N	0.998
X:48478111:C:A	R22S	0.998
X:48478120:A:C	S25R	0.998
X:48478122:C:A	S25R	0.998
X:48478122:C:G	S25R	0.998
X:48478129:A:G	K28E	0.998
X:48478130:A:T	K28I	0.998
X:48478464:T:A	V46D	0.998
X:48478485:G:A	G53D	0.998
X:48478492:G:C	W55C	0.998
X:48478492:G:T	W55C	0.998
X:48478493:A:C	S56R	0.998
X:48478495:C:A	S56R	0.998
X:48478495:C:G	S56R	0.998
X:48479098:T:C	C115R	0.998
X:48479104:G:T	G117W	0.998
X:48481342:G:C	K156N	0.998
X:48481342:G:T	K156N	0.998
X:48481429:T:C	F158L	0.998

dbSNP variants (sampled 300 via entrez): RS1000725305 (X:48480624 G>A,C), RS1002559997 (X:48485344 A>T), RS1002826914 (X:48475285 C>T), RS1005744829 (X:48482015 A>G), RS1006339403 (X:48474612 G>A), RS1006695802 (X:48484269 A>G), RS1006748058 (X:48484771 G>A), RS1007231626 (X:48477427 G>C), RS1007697132 (X:48486632 C>T), RS1007756871 (X:48477069 C>T), RS1008147729 (X:48478976 A>C,G), RS1009148187 (X:48480747 G>T), RS1009200618 (X:48481268 A>C), RS1010204484 (X:48484094 G>C), RS1011215712 (X:48486490 T>C)

Disease associations

OMIM: gene MIM:300499 | disease phenotypes: MIM:309549, MIM:117550

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 9	Definitive	X-linked
non-syndromic X-linked intellectual disability	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Definitive	XL

Mondo (5): intellectual disability, X-linked 9 (MONDO:0010660), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), Sotos syndrome (MONDO:0019349), non-syndromic X-linked intellectual disability (MONDO:0019181)

Orphanet (4): X-linked non-syndromic intellectual disability (Orphanet:777), Sotos syndrome (Orphanet:821), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000179	Thick lower lip vermilion
HP:0000400	Macrotia
HP:0000629	Periorbital fullness
HP:0000637	Long palpebral fissure
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0002194	Delayed gross motor development
HP:0002342	Moderate intellectual disability
HP:0003593	Infantile onset
HP:0005280	Depressed nasal bridge
HP:0009882	Short distal phalanx of finger
HP:0011463	Childhood onset
HP:0100753	Schizophrenia

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D058495	Sotos Syndrome	C16.131.077.889; C16.131.260.905; C16.320.180.905
C563137	Mental Retardation, X-Linked 9 (supp.)
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Nickel	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
cylindrospermopsin	increases expression	1
Fulvestrant	increases methylation, affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	increases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2XB	Abcam HEK293T FTSJ1 KO	Transformed cell line	Female
CVCL_SP00	HAP1 FTSJ1 (-) 1	Cancer cell line	Male
CVCL_XN94	HAP1 FTSJ1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder