FTSJ1

protein-coding

FtsJ RNA 2'-O-methyltransferase 1, the group of 7BS 2'O-ribose DNA/RNA methyltransferases

Gene summary

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. [provided by RefSeq, Aug 2013]

Previous symbols:

MRX9
MRX44

MANE transcript

NM_012280.4

Inheritance

ClinVar variants

P:16U:82B:36

Top phenotype

Intellectual developmental disorder, X-linked 9

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:48,476,021-48,486,364

External References & Databases

Ensembl (ENSG00000068438)

Transcript & Mutation Effects

hg38 • Region Span ~10.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, X-linked 9STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010660

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, X-linked 9DEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010660

Submitter: G2P

X-linked complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0100148

Submitter: ClinGen

The *FTSJ1* gene is a member of the methyltransferase superfamily involved in the processing and modification of ribosomal RNA. *FTSJ1* was first reported in relation to X-linked complex neurodevelopmental disorder in 2004 by Freude *et al*. (PMID: 15162322) who reported loss-of-function variants in two multigenerational families with several affected males and one male proband with non-syndromic intellectual disability. At least 9 variants have been reported, including 5 splice-site, 2 nonsense, 1 frameshift, and 1 missense variant with altered protein function (PMIDs: 15162322, 15342698, 18081026, 26310293, 31170314, 31981491, 36720500). Of note, missense variants without functional characterization were of unclear pathogenicity and were not scored (PMIDs: 25644381, 28330790). Segregation evidence is available from three families with more than three affected members each (PMIDs: 15162322, 15342698). Affected males exhibit mild to moderate intellectual disability and behavior problems, including autism spectrum disorder in some; at least two individuals had seizures or abnormal EEG. Carrier females are unaffected. This gene-disease relationship is also supported by experimental evidence, including biochemical function (PMID: 304115557), functional alteration in patient cells (PMID: 26310293), and mouse models (PMIDs: 30557699, 33771871). In summary, there is definitive evidence supporting the relationship between *FTSJ1* and X-linked complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on February 1, 2023 (SOP Version 9). This gene-disease pair was originally evaluated on January 17, 2018 and classified as moderate. Curation of additional genetic and experimental evidence resulted in the classification being updated.

non-syndromic X-linked intellectual disabilitySUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0019181

Submitter: Orphanet

intellectual developmental disorder, X-linked 9STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010660

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked 9XL

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 8288232; 10398246; 12239714; 15162322; 15342698; 18081026

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FTSJ1 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 74

Inborn genetic diseasesTotal: 34

not specifiedTotal: 18

Intellectual disability, X-linked 9Total: 15

FTSJ1-related disorderTotal: 11

Intellectual disabilityTotal: 5

FTSJ1-related disordersTotal: 2

History of neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012280.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	20 clinvar	3 clinvar	31
missense	2 clinvar	3 clinvar	61 clinvar	10 clinvar	3 clinvar	79
nonsense	1 clinvar	1 clinvar				2
start loss			1 clinvar			1
frameshift	5 clinvar	1 clinvar	1 clinvar			7
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	11 clinvar			14
Total	10	6	82	30	6	134

Highest pathogenic variant AF is 0.000009077705

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012280.4	RefSeq	NP_036412.1	11	MANE Select
ENST00000348411.3	Ensembl	ENSP00000326948.2	11	MANE Select
NM_001282157.2	RefSeq	NP_001269086.1	7	Standard
NM_001441195.1	RefSeq	NP_001428124.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA

Biological Process

tRNA nucleoside ribose methylation
cytoplasmic translation
tRNA modification
tRNA methylation

Molecular Function

tRNA methyltransferase activity
tRNA (guanosine-2'-O-)-methyltransferase activity
tRNA (cytosine-2'-O-)-methyltransferase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000348411
Coding exons: 11
Length: 10212
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.17	73	147	0.496	0.0000126	2137
Missense (PolyPhen)		8	51.464	0.15545		703
Synonymous	0.460	55	59.5	0.924	0.00000504	659
Loss of Function	3.54	0	14.6	0.00	0.00000109	221

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs. {ECO:0000255|HAMAP-Rule:MF_03162}.;

Recessive Scores

pRec: 0.177

Intolerance Scores

RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium