intellectual disability, X-linked 9

Summary

intellectual disability, X-linked 9 (MONDO:0010660) is a disease caused by FTSJ1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: FTSJ1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 9
Mondo ID	MONDO:0010660
MeSH	C563137
OMIM	309549
DOID	DOID:0112034
UMLS	C0796215
MedGen	167112
GARD	0022700
Is cancer (heuristic)	no

Also known as: FTSJ1 non-syndromic X-linked intellectual disability · intellectual developmental disorder, X-linked 9, X-linked recessive · intellectual disability, X-linked 9 · intellectual disability, X-linked type 9 · mental retardation, X-linked 44 · mental retardation, X-linked 9 · mental retardation, X-linked type 9 · MRX9 · non-syndromic X-linked intellectual disability caused by mutation in FTSJ1

Data availability: 14 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › non-syndromic X-linked intellectual disability › intellectual disability, X-linked 9

Related subtypes (51): intellectual disability, X-linked 23, intellectual disability, X-linked 20, intellectual disability, X-linked 14, intellectual disability, X-linked 50, intellectual disability, X-linked 21, intellectual disability, X-linked 58, intellectual disability, X-linked 72, intellectual disability, X-linked 53, intellectual disability, X-linked 73, intellectual disability, X-linked 42, intellectual disability, X-linked 63, intellectual disability, X-linked, with or without seizures, ARX-related, intellectual disability, X-linked 2, intellectual disability, X-linked 81, intellectual disability, X-linked 46, intellectual disability, X-linked 77, intellectual disability, X-linked 45, intellectual disability, X-linked 84, intellectual disability, X-linked 82, intellectual disability, X-linked 30, intellectual disability, X-linked 91, intellectual disability, X-linked 93, chromosome Xp11.22 duplication syndrome, intellectual disability, X-linked 95, intellectual disability, X-linked 96, intellectual disability, X-linked 97, intellectual disability, X-linked 19, intellectual disability, X-linked 89, intellectual disability, X-linked 41, intellectual disability, X-linked 90, intellectual disability, X-linked 92, intellectual disability, X-linked 88, intellectual disability, X-linked 99, intellectual disability, X-linked 100, intellectual disability, X-linked 101, intellectual disability, X-linked 102, intellectual disability, X-linked 61, intellectual disability, X-linked 103, intellectual disability, X-linked 104, intellectual disability, X-linked 105, intellectual disability, X-linked 1, methylmalonic acidemia with homocystinuria, type cblX, FRAXE intellectual disability, intellectual developmental disorder, X-linked 108, intellectual disability, X-linked 106, intellectual disability, X-linked 107, intellectual developmental disorder, X-linked 110, intellectual developmental disorder, X-linked 111, intellectual developmental disorder, X-linked 112, intellectual developmental disorder, X-linked 113, intellectual developmental disorder, X-linked 114

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

14 retrieved; paginated sample, class counts are floors:

5 pathogenic, 5 uncertain significance, 3 likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
10894	NM_012280.4(FTSJ1):c.655G>A (p.Asp219Asn)	FTSJ1	Pathogenic	criteria provided, multiple submitters, no conflicts
10895	NM_012280.4(FTSJ1):c.196C>T (p.Gln66Ter)	FTSJ1	Pathogenic	no assertion criteria provided
10896	NM_012280.4(FTSJ1):c.121+1del	FTSJ1	Pathogenic	no assertion criteria provided
10897	NM_012280.4(FTSJ1):c.192-2A>G	FTSJ1	Pathogenic	no assertion criteria provided
975240	NM_012280.4(FTSJ1):c.256del (p.Val86fs)	FTSJ1	Pathogenic	no assertion criteria provided
3897579	NM_012280.4(FTSJ1):c.587G>A (p.Cys196Tyr)	FTSJ1	Likely pathogenic	criteria provided, single submitter
3900670	NM_012280.4(FTSJ1):c.-88+644_-88+645del	FTSJ1	Likely pathogenic	no assertion criteria provided
4293311	NM_012280.4(FTSJ1):c.759+1G>A	FTSJ1	Likely pathogenic	criteria provided, single submitter
1333963	NM_012280.4(FTSJ1):c.469A>G (p.Ile157Val)	FTSJ1	Uncertain significance	criteria provided, single submitter
1695296	NM_012280.4(FTSJ1):c.70C>T (p.Arg24Cys)	FTSJ1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1809697	NM_012280.4(FTSJ1):c.*9G>A	FTSJ1	Uncertain significance	criteria provided, single submitter
3359023	NM_012280.4(FTSJ1):c.283-12CT[2]	FTSJ1	Uncertain significance	criteria provided, single submitter
431367	NM_012280.4(FTSJ1):c.742C>T (p.Arg248Cys)	FTSJ1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339858	NM_012280.4(FTSJ1):c.620del (p.Pro207fs)	FTSJ1	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FTSJ1	Definitive	X-linked	intellectual disability, X-linked 9	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FTSJ1	Orphanet:777	X-linked non-syndromic intellectual disability

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FTSJ1	HGNC:13254	ENSG00000068438	Q9UET6	tRNA (cytidine(32)/guanosine(34)-2’-O)-methyltransferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FTSJ1	tRNA (cytidine(32)/guanosine(34)-2’-O)-methyltransferase	Methylates the 2’-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FTSJ1	Other/Unknown	no		RNA_MeTrfase_FtsJ_dom, rRNA-MeTfrase_E, RNA_methyltr_E_TRM7

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
granulocyte	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FTSJ1	292	ubiquitous	marker	stromal cell of endometrium, granulocyte, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FTSJ1	2,850

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FTSJ1	Q9UET6	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA modification in the nucleus and cytosol	1	292.8×	0.003	FTSJ1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tRNA nucleoside ribose methylation	1	8426.0×	4e-04	FTSJ1
wobble position ribose methylation	1	8426.0×	4e-04	FTSJ1
tRNA modification	1	601.9×	0.003	FTSJ1
tRNA methylation	1	581.1×	0.003	FTSJ1
neurogenesis	1	208.1×	0.005	FTSJ1
cytoplasmic translation	1	185.2×	0.005	FTSJ1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FTSJ1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FTSJ1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FTSJ1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.