RNA-binding protein 8A

The gene encodes an mRNA binding protein predominantly located in the nucleus, but also found in cytoplasm. Biallelic variants including a pathogenic variant on one allele and a rare variant on the other allel cause TAR syndrome (thrombocytopenia-absent radius).

Gene Structure

The gene resides on chromosome 1 (1q21.1). It consists of 6 exons and contains a conserved mRNA binding motif (codons 67-151, exon 3-5). There is only one single transcript and protein known (NM_005105 -> NP_005096). The gene is translated in centromer-to-telomer direction. A similar pseudogene, RBM8B, exists on chromosome 14 (14q23.1).

Expression

The protein is associated with spliced mRNA in the nucleus and newly exported mRNA in the cytoplasm.

Gene Regulation

The protein is probably bound to mRNA during splicing and remains bound as indicator where introns have been removed.

Interpretation

A pathogenic variant on one allele and a rare variant on the other allel result in a TAR syndrome (thrombocytopenia-absent radius). These rare variants are probably a hypomorphic mutations as in a biallelic case do not cause a disease and on the other hand biallelic pathogenic variants are probably lethal.

Genetests:

Related Diseases:

TAR syndrome
	RBM8A

References:

1.	Zhao XF et al. (2000) MAGOH interacts with a novel RNA-binding protein.

2.	Conklin DC et al. (2000) Cloning and gene expression of a novel human ribonucleoprotein.

3.	Salicioni AM et al. (2000) Identification and structural analysis of human RBM8A and RBM8B: two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor.

4.	Kataoka N et al. (2000) Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm.

5.	Kim VN et al. (2001) The Y14 protein communicates to the cytoplasm the position of exon-exon junctions.

6.	Hachet O et al. (2001) Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport.

7.	Hachet O et al. (2004) Splicing of oskar RNA in the nucleus is coupled to its cytoplasmic localization.

8.	Klopocki E et al. (2007) Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome.

9.	Albers CA et al. (2012) Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome.