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Alternative titles; symbolsCHROMOSOME 3 OPEN READING FRAME 34; C3ORF34HGNC Approved Gene Symbol: CEP19Cytogenetic location: 3q29 Genomic coordinates (GRCh38)...

Alternative titles; symbols


HGNC Approved Gene Symbol: CEP19

Cytogenetic location: 3q29 Genomic coordinates (GRCh38): 3:196,706,276-196,712,249 (from NCBI)

▼ Description
CEP19 localizes to the mother centriole and to the basal body and is involved in cilia assembly (Nishijima et al., 2017).

▼ Cloning and Expression
By mass spectrometry, Jakobsen et al. (2011) identified CEP19, which they called C3ORF34, as a protein that purified with centrosomes from human cell lines. Fluorescence-tagged CEP19 colocalized with a marker for the mother centriole.

Using linkage analysis and positional cloning, Shalata et al. (2013) identified CEP19 within a region of chromosome 3 linked to morbid obesity (see 601665). The deduced 167-amino acid protein has a calculated molecular mass of 19.6 kD. PCR analysis detected CEP19 expression in all 21 human tissues examined, in several human cell lines, and in differentiating 3T3-L1 mouse adipocytes. CEP19 localized to the centrosome and primary cilia. Database analysis identified orthologs of CEP19 in mammals, amphibians, birds, fish, and some early invertebrates, but not in Drosophila, yeast, or C. elegans.

▼ Gene Structure
Shalata et al. (2013) determined that the CEP19 gene contains 3 exons and spans 5.7 kb.

▼ Mapping
Shalata et al. (2013) reported that the CEP19 gene maps to chromosome 3q29.

▼ Gene Function
Nishijima et al. (2017) found that CEP19 interacted with the small GTPase RABL2 (see RABL2B, 605413) and that the interaction recruited RABL2 to the mother centriole and basal body. CEP19 was likely recruited to the centriole via interaction with FGFR1OP (605392). Mutation analysis revealed that an N-terminal domain of CEP19 interacted with the C-terminal domain of FGFR1OP and that a C-terminal region of CEP19 interacted with RABL2. In its GTP-bound form, RABL2 also interacted with the anterograde intraflagellar transport (IFT)-B complex via the IFT74 (608040)-IFT81 (605489) heterodimer, but not with either IFT protein alone. RABL2 appeared to recruit the IFT74-IFT81 dimer to the ciliary base. Interaction of RABL2 with CEP19 or with IFT74-IFT81 was mutually exclusive. CRISPR-Cas9-mediated deletion of CEP19 abolished RABL2 localization at centrosomes and reduced the rate of ciliogenesis in RPE1 cells.

By mass spectrometric analysis, Kanie et al. (2017) found that CEP19 interacted with RABL2B, FGFR1OP, and CEP350 (617870) in human RPE1 cells. Protein pull-down and knockout experiments revealed interaction of CEP19 with the FGFR1OP-CEP350 dimer at the ciliary base, followed by recruitment of RABL2B. GTP-bound RABL2B then bound the IFT-B holocomplex via the IFT74-IFT81 dimer to capture and trigger entry of the IFT-B holocomplex into cilia prior to motor-driven anterograde intraflagellar transport. Knockdown of any of these proteins caused variable ciliation delays in RPE1 cells.

▼ Molecular Genetics
In a large multigenerational Arab family with morbid obesity and spermatogenic failure mapping to chromosome 3q29 (MOSPGF; 615703), Shalata et al. (2013) analyzed 23 genes within the critical region and identified homozygosity for a nonsense mutation in the CEP19 gene (615586.0001) that segregated with obesity in the family and was not found in 620 controls, including 200 ethnically matched individuals, or in the dbSNP database (build 137).

▼ Animal Model
Shalata et al. (2013) obtained Cep19 -/- mice at the expected mendelian ratio. Cep19 -/- mice appeared normal at birth, but they grew significantly larger than their wildtype littermates in both length and mass. They became morbidly obese, with approximately twice the weight of normal individuals, and were also hyperphagic, glucose intolerant, insulin resistant, and infertile. In Cep19 -/- testis, both spermatogenic cells and seminiferous tubules showed marked degeneration, and sperm had an abnormal crooked appearance and diminished motility.

▼ ALLELIC VARIANTS ( 1 Selected Example):

In a large multigenerational Arab family with morbid obesity and spermatogenic failure (MOSPGF; 615703), Shalata et al. (2013) identified homozygosity for a c.244C-T transition in exon 2 of the CEP19 gene, resulting in an arg82-to-ter (R82X) substitution. The mutation segregated with disease in the family and was not found in 620 controls, including 200 ethnically matched individuals, or in the dbSNP database (build 137). Transfection studies indicated that the truncated CEP19 was unstable and degraded through the proteasome pathway.

Tags: 3q29