Alternative titles; symbols
HGNC Approved Gene Symbol: SMOC2
Cytogenetic location: 6q27 Genomic coordinates (GRCh38) : 6:168,441,184-168,667,992 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6q27 | Dentin dysplasia, type I, with microdontia and misshapen teeth | 125400 | Autosomal recessive | 3 |
Nishimoto et al. (2002) identified SMAP2 in an aorta 3-prime-directed cDNA library and obtained the full-length clone from a heart cDNA library. The deduced 446-amino acid protein contains 2 thyroglobulin type-1 domains, 2 EF-hand calcium-binding domains, and a putative signal peptide. It shares 94% sequence identity with mouse Smoc2. RNA dot blot analysis revealed highest expression in skeletal muscle, heart, ovary, testis, bladder, uterus, stomach, small intestine, colon, thyroid gland, mammary gland, and prostate. Weak expression was detected in all other tissues tested.
By RT-PCR, Bloch-Zupan et al. (2011) demonstrated widespread expression of SMOC2 in human tissues, including skin, liver, muscle, lung, spleen, colon, pancreas, and kidney. Analysis of Smoc2 expression during mouse orodental development revealed greater Smoc2 expression in molar than in incisor germs, and Smoc2 expression was found in the oral ectoderm and outer dental epithelium at embryonic day 14.5 and in mesenchymal papillae facing the epithelial loops of molars and the only lingual loop of incisors.
The International Radiation Hybrid Mapping Consortium mapped the SMOC2 gene to chromosome 6 (WI-13584).
Using an intraluminal balloon injury model of the rat carotid artery, Nishimoto et al. (2002) found that Smap2 mRNA was upregulated by day 3 post balloon injury, peaked at day 7, and sustained at elevated levels for 14 days. Upregulation accompanied the proliferation and migration of medial vascular smooth muscle cells into the intima.
Bloch-Zupan et al. (2011) performed knockdown of smoc2 in zebrafish and observed pharyngeal teeth that had abnormalities reminiscent of the human phenotype. In addition, smoc2 depletion in zebrafish altered the expression of 3 major genes involved in odontogenesis: dlx2 (126255), bmp2 (112261), and pitx2 (601542).
In 2 affected first cousins from a consanguineous Turkish pedigree with a form of type I dentin dysplasia associated with extreme microdontia and misshapen teeth and mapping to chromosome 6q27-qter (see 125400), Bloch-Zupan et al. (2011) identified homozygosity for a splice site mutation in the candidate gene SMOC2 (607223.0001).
In 3 affected sibs from a consanguineous Pakistani family with oligodontia, microdontia, and abnormally shaped teeth, AlFawaz et al. (2013) identified homozygosity for a nonsense mutation in the SMOC2 gene (C227X; 607223.0002). The mutation segregated with disease in the family and was not found in public variant databases.
In 2 affected first cousins from a consanguineous Turkish pedigree with a form of type I dentin dysplasia associated with extreme microdontia and misshapen teeth (see 125400), Bloch-Zupan et al. (2011) identified homozygosity for an 84+1G-T transversion at the donor splice site in intron 1 of the SMOC2 gene. The unaffected parents and sibs were heterozygous for the mutation, which was not found in 112 ethnically matched controls.
In 3 affected sibs from a consanguineous Pakistani family with oligodontia, microdontia, and abnormally shaped teeth (see 125400), AlFawaz et al. (2013) identified homozygosity for a c.681T-A transversion (c.681T-A, NM_022138.2) in exon 8 of the SMOC2 gene, resulting in a cys227-to-ter (C227X) substitution. Their first-cousin parents and 3 unaffected sibs were each heterozygous for the mutation, which was not found in the dbSNP, 1000 Genomes Project, or NHLBI Exome Variant Project databases.
AlFawaz, S., Fong, F., Plagnol, V., Wong, F. S. L., Fearne, J., Kelsell, D. P. Recessive oligodontia linked to a homozygous loss-of-function mutation in the SMOC2 gene. Arch. Oral Biol. 58: 462-466, 2013. [PubMed: 23317772] [Full Text: https://doi.org/10.1016/j.archoralbio.2012.12.008]
Bloch-Zupan, A., Jamet, X., Etard, C., Laugel, V., Muller, J., Geoffroy, V., Strauss, J.-P., Pelletier, V., Marion, V., Poch, O., Strahle, U., Stoetzel, C., Dollfus, H. Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects. Am. J. Hum. Genet. 89: 773-781, 2011. [PubMed: 22152679] [Full Text: https://doi.org/10.1016/j.ajhg.2011.11.002]
Nishimoto, S., Hamajima, Y., Toda, Y., Toyoda, H., Kitamura, K., Komurasaki, T. Identification of a novel smooth muscle associated protein, smap2, upregulated during neointima formation in a rat carotid endarterectomy model. Biochim. Biophys. Acta 1576: 225-230, 2002. [PubMed: 12031507] [Full Text: https://doi.org/10.1016/s0167-4781(02)00345-7]