* 300499

FTSJ RNA 2-PRIME-O-METHYLTRANSFERASE 1; FTSJ1


Alternative titles; symbols

FtsJ, E. COLI, HOMOLOG OF, 1
SPB1, S. CEREVISIAE, HOMOLOG OF
JM23


HGNC Approved Gene Symbol: FTSJ1

Cytogenetic location: Xp11.23     Genomic coordinates (GRCh38): X:48,476,021-48,486,364 (from NCBI)


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Xp11.23 Intellectual developmental disorder, X-linked 9 309549 XLR 3

TEXT

Cloning and Expression

Pintard et al. (2000) cloned and characterized Spb1, the S. cerevisiae homolog of E. coli FTSJ1. The deduced 842-amino acid protein contains a 221-amino acid N-terminal S-adenosyl-L-methionine (AdoMet)-binding domain found in AdoMet-dependent methyltransferases. The Spb1 protein localized to the nucleolus. By database analysis, Pintard et al. (2000) identified a human homolog of FTSJ1, which encodes a protein with significant similarity to Spb1 in the AdoMet-binding domain.


Gene Function

Pintard et al. (2000) confirmed that yeast Spb1 binds AdoMet, suggesting that it is a methylase. They found that temperature-sensitive mutant alleles of Spb1 could suppress the deletion of the poly(A)-binding protein gene (Pab1; 604679). The mutant alleles were also associated with reduced 60S ribosome subunit content and abnormalities in the processing of other ribosomal subunits.

FTSJ1 protein is a homolog of Escherichia coli RNA methyltransferase FtsJ/RrmJ and may play a role in the regulation of translation (Freude et al., 2004).


Mapping

The International Radiation Hybrid Mapping Consortium mapped the FTSJ1 gene to the X chromosome (WI-13805).


Molecular Genetics

As could be concluded from the distribution of linkage intervals in 125 families with nonsyndromic X-linked mental retardation, approximately 30% of all relevant mutations cluster on the proximal short arm of the X chromosome (Ropers et al., 2003). PQBP1 (300463) and ZNF41 (314995) are 2 of the genes located in that region in which mutations causing X-linked mental retardation have been found. Freude et al. (2004) found that FTSJ1 is a third such gene. In a family reported by Hamel et al. (1999), and designated MRX44 (XLID9; 309549), Freude et al. (2004) found a mutation in the FTSJ1 gene (300499.0001). Other mutations in this gene were found in 2 other families.

In a large Belgian family with nonsyndromic X-linked mental retardation designated MRX9 (XLID9; 309549), Ramser et al. (2004) identified a splice site mutation in the FTSJ1 gene (300499.0004). The findings indicated that the FTSJ1 protein, which may be associated with ribosomal stability, is associated with X-linked mental retardation.


ALLELIC VARIANTS ( 4 Selected Examples):

.0001 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, EX9DEL
   RCV000011641...

In the family reported by Hamel et al. (1999) and designated MRX44 (XLID9; 309549), affected males had mild to moderate mental retardation. Freude et al. (2004) found a single-nucleotide substitution (655G-A) at the last nucleotide of exon 9 in this family. Subsequent amplification of patient cDNA resulted in a fragment that was smaller than expected; direct sequencing of this specific product showed that exon 9 was absent. The absence introduced no frameshift in the FTSJ1 open reading frame, but the resulting FTSJ1 protein lacked 28 amino acids, which altered its structure and probably also its function.


.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, 196C-T
  
RCV000011642

After the finding of the FTSJ1 mutation in the original MRX44 family (XLID9; 309549), Freude et al. (2004) searched for mutations in this gene in 215 individuals from unrelated families with putative X-linked metal retardation for which no linkage data were available. This analysis resulted in detection of a single-nucleotide substitution (196C-T) in exon 4, resulting in a predicted truncated protein of 65 amino acids.


.0003 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, IVS2, G DEL, +1
   RCV000011643

In 1 family with presumed nonsyndromic X-linked intellectual developmental disorder (XLID9; 309549), Freude et al. (2004) found a single-nucleotide deletion, IVS2+1delG. The deletion affected 1 of the 2 guanine nucleotides of the exon 2/intron 2 boundary. Direct sequencing of mutant RT-PCR products from the patient showed that, at the boundary between exon 2 and exon 3, the transcript carried an insertion of a 10-bp sequence of intron 2, which indicated that the IVS2+1delG deletion affected splicing by cryptic splice site activation. The incorporation of intronic sequence led to a frameshift in the FTSJ1 mRNA that resulted in the use of a premature stop codon in exon 3 at position 138, presumably producing a truncated protein of 49 amino acids.


.0004 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, IVS3AS, A-G, -2
  
RCV000011644

In a Belgian family with X-linked intellectual developmental disorder-9 (XLID9; 309549), previously described by Willems et al. (1993), Ramser et al. (2004) identified an A-to-G transition in the conserved acceptor splice site of intron 3 (IVS3-2A-G) of the FTSJ1 gene. The mutation resulted in skipping of exon 4 and introduced a premature stop codon in exon 5, leading to a severely truncated protein.


REFERENCES

  1. Freude, K., Hoffmann, K., Jensen, L.-R., Delatycki, M. B., des Portes, V., Moser, B., Hamel, B., van Bokhoven, H., Moraine, C., Fryns, J.-P., Chelly, J., Gecz, J., Lenzner, S., Kalscheuer, V. M., Ropers, H.-H. Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. Am. J. Hum. Genet. 75: 305-309, 2004. [PubMed: 15162322, images, related citations] [Full Text]

  2. Hamel, B. C. J., Smits, A. P. T., van den Helm, B., Smeets, D. F. C. M., Knoers, N. V. A. M., van Roosmalen, T., Thoonen, G. H. J., Assman-Hulsmans, C. F. C. H., Ropers, H.-H., Mariman, E. C. M., Kremer, H. Four families (MRX43, MRX44, MRX45, MRX52) with nonspecific X-linked mental retardation: clinical and psychometric data and results of linkage analysis. Am. J. Med. Genet. 85: 290-304, 1999. [PubMed: 10398246, related citations]

  3. Pintard, L., Kressler, D., Lapeyre, B. Spb1p is a yeast nucleolar protein associated with Nop1p and Nop58p that is able to bind S-adenosyl-L-methionine in vitro. Molec. Cell. Biol. 20: 1370-1381, 2000. [PubMed: 10648622, images, related citations] [Full Text]

  4. Ramser, J., Winnepenninckx, B., Lenski, C., Errijgers, V., Platzer, M., Schwartz, C. E., Meindl, A., Kooy, R. F. A splice site mutation in the methyltransferase gene FTSJ1 in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9). J. Med. Genet. 41: 679-683, 2004. [PubMed: 15342698, related citations] [Full Text]

  5. Ropers, H. H., Hoeltzenbein, M., Kalscheuer, V., Yntema, H., Hamel, B., Fryns, J. P., Chelly, J., Partington, M., Gecz, J., Moraine, C. Nonsyndromic X-linked mental retardation: where are the missing mutations? Trends Genet. 19: 316-320, 2003. [PubMed: 12801724, related citations] [Full Text]

  6. Willems, P., Vits, L., Buntinx, I., Raeymaekers, P., Van Broeckhoven, C., Ceulemans, B. Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome. Genomics 18: 290-294, 1993. [PubMed: 8288232, related citations] [Full Text]


Victor A. McKusick - updated : 10/12/2004
Victor A. McKusick - updated : 7/12/2004
Creation Date:
Patricia A. Hartz : 7/2/2004
alopez : 08/20/2021
mgross : 04/30/2019
carol : 02/01/2007
tkritzer : 10/14/2004
terry : 10/12/2004
alopez : 7/14/2004
terry : 7/12/2004
carol : 7/2/2004

* 300499

FTSJ RNA 2-PRIME-O-METHYLTRANSFERASE 1; FTSJ1


Alternative titles; symbols

FtsJ, E. COLI, HOMOLOG OF, 1
SPB1, S. CEREVISIAE, HOMOLOG OF
JM23


HGNC Approved Gene Symbol: FTSJ1

Cytogenetic location: Xp11.23     Genomic coordinates (GRCh38): X:48,476,021-48,486,364 (from NCBI)


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Xp11.23 Intellectual developmental disorder, X-linked 9 309549 X-linked recessive 3

TEXT

Cloning and Expression

Pintard et al. (2000) cloned and characterized Spb1, the S. cerevisiae homolog of E. coli FTSJ1. The deduced 842-amino acid protein contains a 221-amino acid N-terminal S-adenosyl-L-methionine (AdoMet)-binding domain found in AdoMet-dependent methyltransferases. The Spb1 protein localized to the nucleolus. By database analysis, Pintard et al. (2000) identified a human homolog of FTSJ1, which encodes a protein with significant similarity to Spb1 in the AdoMet-binding domain.


Gene Function

Pintard et al. (2000) confirmed that yeast Spb1 binds AdoMet, suggesting that it is a methylase. They found that temperature-sensitive mutant alleles of Spb1 could suppress the deletion of the poly(A)-binding protein gene (Pab1; 604679). The mutant alleles were also associated with reduced 60S ribosome subunit content and abnormalities in the processing of other ribosomal subunits.

FTSJ1 protein is a homolog of Escherichia coli RNA methyltransferase FtsJ/RrmJ and may play a role in the regulation of translation (Freude et al., 2004).


Mapping

The International Radiation Hybrid Mapping Consortium mapped the FTSJ1 gene to the X chromosome (WI-13805).


Molecular Genetics

As could be concluded from the distribution of linkage intervals in 125 families with nonsyndromic X-linked mental retardation, approximately 30% of all relevant mutations cluster on the proximal short arm of the X chromosome (Ropers et al., 2003). PQBP1 (300463) and ZNF41 (314995) are 2 of the genes located in that region in which mutations causing X-linked mental retardation have been found. Freude et al. (2004) found that FTSJ1 is a third such gene. In a family reported by Hamel et al. (1999), and designated MRX44 (XLID9; 309549), Freude et al. (2004) found a mutation in the FTSJ1 gene (300499.0001). Other mutations in this gene were found in 2 other families.

In a large Belgian family with nonsyndromic X-linked mental retardation designated MRX9 (XLID9; 309549), Ramser et al. (2004) identified a splice site mutation in the FTSJ1 gene (300499.0004). The findings indicated that the FTSJ1 protein, which may be associated with ribosomal stability, is associated with X-linked mental retardation.


ALLELIC VARIANTS 4 Selected Examples):

.0001   INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, EX9DEL
ClinVar: RCV000011641, RCV003114186

In the family reported by Hamel et al. (1999) and designated MRX44 (XLID9; 309549), affected males had mild to moderate mental retardation. Freude et al. (2004) found a single-nucleotide substitution (655G-A) at the last nucleotide of exon 9 in this family. Subsequent amplification of patient cDNA resulted in a fragment that was smaller than expected; direct sequencing of this specific product showed that exon 9 was absent. The absence introduced no frameshift in the FTSJ1 open reading frame, but the resulting FTSJ1 protein lacked 28 amino acids, which altered its structure and probably also its function.


.0002   INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, 196C-T
SNP: rs1602048836, ClinVar: RCV000011642

After the finding of the FTSJ1 mutation in the original MRX44 family (XLID9; 309549), Freude et al. (2004) searched for mutations in this gene in 215 individuals from unrelated families with putative X-linked metal retardation for which no linkage data were available. This analysis resulted in detection of a single-nucleotide substitution (196C-T) in exon 4, resulting in a predicted truncated protein of 65 amino acids.


.0003   INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, IVS2, G DEL, +1
ClinVar: RCV000011643

In 1 family with presumed nonsyndromic X-linked intellectual developmental disorder (XLID9; 309549), Freude et al. (2004) found a single-nucleotide deletion, IVS2+1delG. The deletion affected 1 of the 2 guanine nucleotides of the exon 2/intron 2 boundary. Direct sequencing of mutant RT-PCR products from the patient showed that, at the boundary between exon 2 and exon 3, the transcript carried an insertion of a 10-bp sequence of intron 2, which indicated that the IVS2+1delG deletion affected splicing by cryptic splice site activation. The incorporation of intronic sequence led to a frameshift in the FTSJ1 mRNA that resulted in the use of a premature stop codon in exon 3 at position 138, presumably producing a truncated protein of 49 amino acids.


.0004   INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9

FTSJ1, IVS3AS, A-G, -2
SNP: rs1602048728, ClinVar: RCV000011644

In a Belgian family with X-linked intellectual developmental disorder-9 (XLID9; 309549), previously described by Willems et al. (1993), Ramser et al. (2004) identified an A-to-G transition in the conserved acceptor splice site of intron 3 (IVS3-2A-G) of the FTSJ1 gene. The mutation resulted in skipping of exon 4 and introduced a premature stop codon in exon 5, leading to a severely truncated protein.


REFERENCES

  1. Freude, K., Hoffmann, K., Jensen, L.-R., Delatycki, M. B., des Portes, V., Moser, B., Hamel, B., van Bokhoven, H., Moraine, C., Fryns, J.-P., Chelly, J., Gecz, J., Lenzner, S., Kalscheuer, V. M., Ropers, H.-H. Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. Am. J. Hum. Genet. 75: 305-309, 2004. [PubMed: 15162322] [Full Text: https://doi.org/10.1086/422507]

  2. Hamel, B. C. J., Smits, A. P. T., van den Helm, B., Smeets, D. F. C. M., Knoers, N. V. A. M., van Roosmalen, T., Thoonen, G. H. J., Assman-Hulsmans, C. F. C. H., Ropers, H.-H., Mariman, E. C. M., Kremer, H. Four families (MRX43, MRX44, MRX45, MRX52) with nonspecific X-linked mental retardation: clinical and psychometric data and results of linkage analysis. Am. J. Med. Genet. 85: 290-304, 1999. [PubMed: 10398246]

  3. Pintard, L., Kressler, D., Lapeyre, B. Spb1p is a yeast nucleolar protein associated with Nop1p and Nop58p that is able to bind S-adenosyl-L-methionine in vitro. Molec. Cell. Biol. 20: 1370-1381, 2000. [PubMed: 10648622] [Full Text: https://doi.org/10.1128/MCB.20.4.1370-1381.2000]

  4. Ramser, J., Winnepenninckx, B., Lenski, C., Errijgers, V., Platzer, M., Schwartz, C. E., Meindl, A., Kooy, R. F. A splice site mutation in the methyltransferase gene FTSJ1 in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9). J. Med. Genet. 41: 679-683, 2004. [PubMed: 15342698] [Full Text: https://doi.org/10.1136/jmg.2004.019000]

  5. Ropers, H. H., Hoeltzenbein, M., Kalscheuer, V., Yntema, H., Hamel, B., Fryns, J. P., Chelly, J., Partington, M., Gecz, J., Moraine, C. Nonsyndromic X-linked mental retardation: where are the missing mutations? Trends Genet. 19: 316-320, 2003. [PubMed: 12801724] [Full Text: https://doi.org/10.1016/S0168-9525(03)00113-6]

  6. Willems, P., Vits, L., Buntinx, I., Raeymaekers, P., Van Broeckhoven, C., Ceulemans, B. Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome. Genomics 18: 290-294, 1993. [PubMed: 8288232] [Full Text: https://doi.org/10.1006/geno.1993.1468]


Contributors:
Victor A. McKusick - updated : 10/12/2004
Victor A. McKusick - updated : 7/12/2004

Creation Date:
Patricia A. Hartz : 7/2/2004

Edit History:
alopez : 08/20/2021
mgross : 04/30/2019
carol : 02/01/2007
tkritzer : 10/14/2004
terry : 10/12/2004
alopez : 7/14/2004
terry : 7/12/2004
carol : 7/2/2004