Alternative titles; symbols
HGNC Approved Gene Symbol: POP1
Cytogenetic location: 8q22.2 Genomic coordinates (GRCh38): 8:98,117,293-98,159,835 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8q22.2 | Anauxetic dysplasia 2 | 617396 | Autosomal recessive | 3 |
Lygerou et al. (1994) demonstrated that an S. cerevisiae gene, designated POP1 for 'processing of precursor RNAs,' encodes a protein component of both RNase P and RNase MRP. RNase P and RNase MRP are 2 small nuclear ribonucleoproteins (snRNPs) that have demonstrated enzymatic activity on RNA substrates in vitro. Mutations in yeast POP1 are lethal. Lygerou et al. (1996) identified a human EST with homology to yeast POP1. Human POP1 encodes a predicted 1,024-amino acid protein that has a pI of 9.86. On Northern blots, human POP1 is expressed as a major 4.1-kb and a minor 6-kb transcript, perhaps due to alternative polyadenylation signals. Anti-POP1 antibodies recognize a doublet of approximately 115 kD on Western blots. In HeLa cells, human POP1 localizes to the nucleus and strongly accumulates in the nucleolus.
Schmiedeknecht et al. (1997) found that p14.5 (602487) and human POP1 are oriented head-to-head, separated by a 102-bp region that contains a bidirectional promoter. Schmiedeknecht et al. (1997) mapped the human POP1 gene to 8q22 using fluorescence in situ hybridization.
Lygerou et al. (1996) performed coimmunoprecipitation studies showing that POP1 is associated with both RNase P and RNase MRP snRNAs, and with RNase P enzymatic activity. Lygerou et al. (1996) found that approximately 50% of Th autoimmune sera recognized POP1.
In 2 sisters with anauxetic dysplasia (ANXD2; 617396), Glazov et al. (2011) identified compound heterozygosity for a nonsense mutation (R513X; 602486.0001) and a missense mutation (G583E; 602486.0002) in the POP1 gene. Their unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in 186 controls or in public variant databases.
In a 5-year-old Moroccan boy with ANXD2, Elalaoui et al. (2016) identified homozygosity for a missense mutation in the POP1 gene (P582S; 602486.0003), for which his first-cousin unaffected parents were heterozygous. The variant was not found in 146 controls or in public variant databases.
In a 4.6-year-old Moroccan girl with severe short stature and relatively mild skeletal dysplasia, Barraza-Garcia et al. (2017) identified compound heterozygosity for the P582S variant and a 1-bp deletion in the POP1 gene (602486.0004), and in a 7-year-old Senegalese boy with suspected ANXD, they identified homozygosity for a POP1 missense mutation (D511Y; 602486.0005). The mutations were present in heterozygosity in the respective parents, and none was found in population databases.
In 2 sisters with anauxetic dysplasia (ANXD2; 617396) Glazov et al. (2011) identified compound heterozygous variants in the POP1 gene: a c.1573C-T transition (c.1573C-T, NM_001145860.1) in exon 10, resulting in an arg513-to-ter (R513X) substitution, and a c.1748G-A transition in exon 12, resulting in a gly583-to-glu (G583E) substitution at a highly conserved residue. The mutations were identified by whole-exome sequencing. Their unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in 186 controls or in public databases, including dbSNP (build 131). RT-PCR of patient cells demonstrated a markedly reduced relative abundance of RMRP RNA and a higher abundance of pre-5.85 rRNA compared to cells from unaffected parents and controls. Analysis of stimulated peripheral blood mononuclear cells showed that the affected sibs had markedly diminished cell proliferation compared with healthy controls, and their father, who carried the R513X mutation, also showed a reduction in cell proliferation rate.
For discussion of the c.1748G-A transition (c.1748G-A, NM_001145860.1) in the POP1 gene, resulting in a gly583-to-glu (G483E) substitution, that was identified in compound heterozygous state in 2 sisters with anauxetic dysplasia (ANXD2; 617396) Glazov et al. (2011), see 602486.0001.
In a 5-year-old Moroccan boy with anauxetic dysplasia (ANXD2; 617396), Elalaoui et al. (2016) identified homozygosity for a c.1744C-T transition in exon 13 of the POP1 gene, resulting in a pro582-to-ser (P582S) substitution at a highly conserved residue. His first-cousin unaffected parents were heterozygous for the variant, which was not found in 146 controls or in public variant databases, including dbSNP (build 131).
In a 4.6-year-old Moroccan girl with severe short stature and relatively mild skeletal dysplasia, Barraza-Garcia et al. (2017) identified compound heterozygosity for mutations in the POP1 gene, including the P582S variant (c.1744C-T, NM_001145860.1), and a 1-bp deletion in exon 16 (c.2607delC; 602486.0004), causing a frameshift predicted to result in a premature termination codon (Glu870fsTer5). Her unaffected parents were each heterozygous for 1 of the mutations, which were not found in the ExAC, ESP, or Kaviar databases.
For discussion of the 1-bp deletion (c.2607delC, NM_001145860.1) in exon 16 of the POP1 gene, causing a frameshift predicted to result in a premature termination codon (Glu870fsTer5), that was found in compound heterozygous state in a Moroccan girl with anauxetic dysplasia (ANXD2; 617396) by Barraza-Garcia et al. (2017), see 602486.0003.
In a 7-year-old Senegalese boy with anauxetic dysplasia (ANXD2; 617396), Barraza-Garcia et al. (2017) identified homozygosity for a c.1531G-T transversion (c.1531G-T, NM_001145860.1) in exon 11 of the POP1 gene, resulting in an asp511-to-tyr (D511Y) substitution at a highly conserved residue. The mutation was present in heterozygosity in his unaffected parents, who were not of known consanguinity but originated from the same village; it was not found in the ExAC, ESP, or Kaviar databases.
Barraza-Garcia, J., Rivera-Pedroza, C. I., Hisado-Oliva, A., Belinchon-Martinez, A., Sentchordi-Montane, L., Duncan, E. L., Clark, G. R., del Pozo, A., Ibanez-Garikano, K., Offiah, A., Prieto-Matos, P., Cormier-Daire, V., Heath, K. E. Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia. Clin. Genet. 92: 91-98, 2017. [PubMed: 28067412] [Full Text: https://doi.org/10.1111/cge.12964]
Elalaoui, S. C., Laarabi, F. Z., Mansouri, M., Mrani, N. A., Nishimura, G., Sefiani, A. Further evidence of POP1 mutations as the cause of anauxetic dysplasia. Am. J. Med. Genet. 170A: 2462-2465, 2016. [PubMed: 27380734] [Full Text: https://doi.org/10.1002/ajmg.a.37839]
Glazov, E. A., Zankl, A., Donskoi, M., Kenna, T. J., Thomas, G. P., Clark, G. R., Duncan, E. L., Brown, M. A. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia. PLoS Genet. 7: e1002027, 2011. Note: Electronic Article. [PubMed: 21455487] [Full Text: https://doi.org/10.1371/journal.pgen.1002027]
Lygerou, Z., Mitchell, P., Petfalski, E., Seraphin, B., Tollervey, D. The POP1 gene encodes a protein component common to the RNase MRP and RNase P ribonucleoproteins. Genes Dev. 8: 1423-1433, 1994. [PubMed: 7926742] [Full Text: https://doi.org/10.1101/gad.8.12.1423]
Lygerou, Z., Pluk, H., van Venrooij, W. J., Seraphin, B. hPop1: an autoantigenic protein subunit shared by the human RNase P and RNase MRP ribonucleoproteins. EMBO J. 15: 5936-5948, 1996. [PubMed: 8918471]
Schmiedeknecht, G., Buchler, C., Schmitz, G. A bidirectional promoter connects the p14.5 gene to the gene for RNase P and RNase MRP protein subunit hPOP1. Biochem. Biophys. Res. Commun. 241: 59-67, 1997. [PubMed: 9405234] [Full Text: https://doi.org/10.1006/bbrc.1997.7772]