 |
VOOZH | about |
|
VOOZH | about |
*613344
Table of Contents
Other entities represented in this entry:
HGNC Approved Gene Symbol: KIAA1549
Cytogenetic location: 7q34 Genomic coordinates (GRCh38) : 7:138,831,381-138,981,389 (from NCBI)
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) identified a partial KIAA1549 cDNA that lacks 5-prime sequence. The ORF covers 1,488 amino acids. RT-PCR ELISA showed variable KIAA1549 expression in all tissues examined. Highest expression was detected in kidney, brain, and several specific brain regions, including amygdala, caudate nucleus, hippocampus, thalamus, and subthalamic nucleus. Lowest expression was detected in spleen.
By database analysis and 5-prime RACE, Jones et al. (2008) identified long and short variants of KIAA1549. The short variants are transcribed from an internal promoter in intron 8. Alternative splicing of the 3-prime terminal exon of KIAA1549 produces 2 different long variants and 2 different short variants.
De Bruijn et al. (2018) analyzed expression of KIAA1549 in human tissues and found low to moderate expression of the long transcript in retina and other tissues such as heart and kidneys, with predominant expression in the brain. However, the less-characterized short transcript showed abundant expression in the retina, approximately 200-fold compared to the reference gene GUSB (611499), with only minimal expression in brain and other tissues. The authors suggested that the short KIAA1549 isoform might have a retina-specific function. In addition, immunofluorescence in retina sections from a 2-month-old mouse revealed colocalization with centrin (see CETN1, 603187) at the connecting cilium of the photoreceptor cells. Positive staining was also observed at the outer plexiform layer of the retina.
Jones et al. (2008) found that the KIAA1549 gene contains 20 exons. Exon 1 is located within a CpG island and contains 2 start ATG codons in frame with exon 2. Intron 8 contains an internal promoter and a start codon.
By PCR of a human-rodent hybrid panel, Nagase et al. (2000) mapped the KIAA1549 gene to chromosome 7. Jones et al. (2008) mapped the KIAA1549 gene to chromosome 7q34 by genomic sequence analysis.
Jones et al. (2008) identified tandem duplications of about 2 Mb at chromosome 7q34 in 29 (66%) of 44 pilocytic astrocytomas (see 137800). These rearrangements were not observed in 244 higher grade astrocytomas. The duplications resulted in 3 different in-frame fusion genes containing most 5-prime exons of the KIAA1549 gene and several 3-prime exons of the BRAF gene (164757). The most common fusion was between KIAA1549 exon 16 and BRAF exon 9, which occurred in 20 pilocytic astrocytomas. All breakpoint variants were expected to encode functionally similar proteins containing the C-terminal kinase domain of BRAF without the N-terminal BRAF autoregulatory domain. Similar to wildtype KIAA1549, which produces a short variant through the use of an internal promoter, PCR analysis detected both long and short variants of the KIAA1549/BRAF fusion transcript. COS-7 cells transfected with either long or short KIAA1549/BRAF fusion transcripts showed constitutive BRAF kinase activity, and NIH3T3 cells transfected with the short KIAA1549/BRAF fusion transcript showed anchorage-independent growth.
In 2 Iranian sibs and a Dutch man with retinitis pigmentosa (RP86; 618613), de Bruijn et al. (2018) identified homozygosity for a 1-bp deletion (c.52del; 613344.0001) and a missense mutation (H1562Q; 613344.0002), respectively, in the KIAA1549 gene.
In a sister and brother, ages 53 and 38 years, from a consanguineous Iranian family with retinitis pigmentosa (RP86; 618613), de Bruijn et al. (2018) identified homozygosity for a 1-bp deletion (c.52del, NM_001164665) in exon 1 of the KIAA1549 gene, causing a frameshift predicted to result in a premature termination codon (Arg18AlafsTer64). Results from segregation analysis in the family were not reported. The mutation was not found in an in-house exome database of 15,576 alleles or in the Iranome, gnomAD, ExAC, or dbSNP databases.
In a 54-year-old Dutch man with retinitis pigmentosa (RP86; 618613), de Bruijn et al. (2018) identified homozygosity for a c.4686C-A transition (c.4686C-A, NM_001164665) in exon 14 of the KIAA1549 gene, resulting in a his1562-to-gln (H1562Q) substitution at a moderately conserved residue within a highly conserved region. His unaffected brother and sister were heterozygous for the mutation.
de Bruijn, S. E., Verbakel, S. K., de Vrieze, E., Kremer, H., Cremers, F. P. M., Hoyng, C. B., van den Born, L. I., Roosing, S. Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa. J. Med. Genet. 55: 705-712, 2018. [PubMed: 30120214, related citations] [Full Text]
Jones, D. T. W., Kocialkowski, S., Liu, L., Pearson, D. M., Backlund, L. M., Ichimura, K., Collins, V. P. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res. 68: 8673-8677, 2008. [PubMed: 18974108, images, related citations] [Full Text]
Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 273-281, 2000. [PubMed: 10997877, related citations] [Full Text]
Other entities represented in this entry:
HGNC Approved Gene Symbol: KIAA1549
Cytogenetic location: 7q34 Genomic coordinates (GRCh38) : 7:138,831,381-138,981,389 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7q34 | Retinitis pigmentosa 86 | 618613 | Autosomal recessive | 3 |
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) identified a partial KIAA1549 cDNA that lacks 5-prime sequence. The ORF covers 1,488 amino acids. RT-PCR ELISA showed variable KIAA1549 expression in all tissues examined. Highest expression was detected in kidney, brain, and several specific brain regions, including amygdala, caudate nucleus, hippocampus, thalamus, and subthalamic nucleus. Lowest expression was detected in spleen.
By database analysis and 5-prime RACE, Jones et al. (2008) identified long and short variants of KIAA1549. The short variants are transcribed from an internal promoter in intron 8. Alternative splicing of the 3-prime terminal exon of KIAA1549 produces 2 different long variants and 2 different short variants.
De Bruijn et al. (2018) analyzed expression of KIAA1549 in human tissues and found low to moderate expression of the long transcript in retina and other tissues such as heart and kidneys, with predominant expression in the brain. However, the less-characterized short transcript showed abundant expression in the retina, approximately 200-fold compared to the reference gene GUSB (611499), with only minimal expression in brain and other tissues. The authors suggested that the short KIAA1549 isoform might have a retina-specific function. In addition, immunofluorescence in retina sections from a 2-month-old mouse revealed colocalization with centrin (see CETN1, 603187) at the connecting cilium of the photoreceptor cells. Positive staining was also observed at the outer plexiform layer of the retina.
Jones et al. (2008) found that the KIAA1549 gene contains 20 exons. Exon 1 is located within a CpG island and contains 2 start ATG codons in frame with exon 2. Intron 8 contains an internal promoter and a start codon.
By PCR of a human-rodent hybrid panel, Nagase et al. (2000) mapped the KIAA1549 gene to chromosome 7. Jones et al. (2008) mapped the KIAA1549 gene to chromosome 7q34 by genomic sequence analysis.
Jones et al. (2008) identified tandem duplications of about 2 Mb at chromosome 7q34 in 29 (66%) of 44 pilocytic astrocytomas (see 137800). These rearrangements were not observed in 244 higher grade astrocytomas. The duplications resulted in 3 different in-frame fusion genes containing most 5-prime exons of the KIAA1549 gene and several 3-prime exons of the BRAF gene (164757). The most common fusion was between KIAA1549 exon 16 and BRAF exon 9, which occurred in 20 pilocytic astrocytomas. All breakpoint variants were expected to encode functionally similar proteins containing the C-terminal kinase domain of BRAF without the N-terminal BRAF autoregulatory domain. Similar to wildtype KIAA1549, which produces a short variant through the use of an internal promoter, PCR analysis detected both long and short variants of the KIAA1549/BRAF fusion transcript. COS-7 cells transfected with either long or short KIAA1549/BRAF fusion transcripts showed constitutive BRAF kinase activity, and NIH3T3 cells transfected with the short KIAA1549/BRAF fusion transcript showed anchorage-independent growth.
In 2 Iranian sibs and a Dutch man with retinitis pigmentosa (RP86; 618613), de Bruijn et al. (2018) identified homozygosity for a 1-bp deletion (c.52del; 613344.0001) and a missense mutation (H1562Q; 613344.0002), respectively, in the KIAA1549 gene.
In a sister and brother, ages 53 and 38 years, from a consanguineous Iranian family with retinitis pigmentosa (RP86; 618613), de Bruijn et al. (2018) identified homozygosity for a 1-bp deletion (c.52del, NM_001164665) in exon 1 of the KIAA1549 gene, causing a frameshift predicted to result in a premature termination codon (Arg18AlafsTer64). Results from segregation analysis in the family were not reported. The mutation was not found in an in-house exome database of 15,576 alleles or in the Iranome, gnomAD, ExAC, or dbSNP databases.
In a 54-year-old Dutch man with retinitis pigmentosa (RP86; 618613), de Bruijn et al. (2018) identified homozygosity for a c.4686C-A transition (c.4686C-A, NM_001164665) in exon 14 of the KIAA1549 gene, resulting in a his1562-to-gln (H1562Q) substitution at a moderately conserved residue within a highly conserved region. His unaffected brother and sister were heterozygous for the mutation.
de Bruijn, S. E., Verbakel, S. K., de Vrieze, E., Kremer, H., Cremers, F. P. M., Hoyng, C. B., van den Born, L. I., Roosing, S. Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa. J. Med. Genet. 55: 705-712, 2018. [PubMed: 30120214] [Full Text: https://doi.org/10.1136/jmedgenet-2018-105364]
Jones, D. T. W., Kocialkowski, S., Liu, L., Pearson, D. M., Backlund, L. M., Ichimura, K., Collins, V. P. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res. 68: 8673-8677, 2008. [PubMed: 18974108] [Full Text: https://doi.org/10.1158/0008-5472.CAN-08-2097]
Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 273-281, 2000. [PubMed: 10997877] [Full Text: https://doi.org/10.1093/dnares/7.4.271]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM