Alternative titles; symbols
HGNC Approved Gene Symbol: TRIM36
Cytogenetic location: 5q22.3 Genomic coordinates (GRCh38): 5:115,124,772-115,180,294 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5q22.3 | ?Anencephaly 1 | 206500 | Autosomal recessive | 3 |
Using a B-box domain consensus sequence to screen EST databases for novel TRIM family members, Reymond et al. (2001) identified and cloned mouse and human TRIM36. The deduced protein contains an N-terminal RING domain, B-box-1 and B-box-2 domains, and a coiled-coil region.
By sequencing a region of chromosome 5 duplicated in a renal cell carcinoma, Balint et al. (2004) identified TRIM36, which they designated RBCC728. They obtained the full-length cDNA by PCR of fetal brain and adult kidney cDNA libraries. The deduced 728-amino acid protein has an N-terminal RING finger C3HC4 structure, 2 B-boxes, a coiled-coil region, a fibronectin type III (see 135600) domain and a C-terminal domain found in SPRY proteins (see SPRY1; 602465). TRIM36 also contains a bipartite nuclear localization signal. TRIM36 shares 26% amino acid identity with MID1 (300552). Quantitative RT-PCR detected highest TRIM36 expression in testis, followed by prostate and brain, with weak expression in kidney, lung, and heart. TRIM36 expression was upregulated in some prostate cancers compared with normal tissue. Immunohistochemical analysis of recombinant and endogenous TRIM36 in COS-7 cells showed the protein expressed in a slightly filamentous staining pattern in the cytoplasm. TRIM36 often accumulated near sites of cell-cell contact, and mitotic cells were negative for TRIM36 staining.
Singh et al. (2017) found expression of the TRIM36 gene in human fetal brain. In zebrafish embryos, it was expressed in the neural plate, neural tube, and a portion of the posterior somite.
Balint et al. (2004) determined that the TRIM36 gene contains 10 exons and spans 55 kb.
By radiation hybrid analysis, Reymond et al. (2001) mapped the TRIM36 gene to chromosome 5q22. By shotgun sequencing, Balint et al. (2004) identified the TRIM36 gene within a BAC mapped to chromosome 5q22.3.
In a 20-week-old fetus, conceived of consanguineous Indian parents, with anencephaly (ANPH1; 206500), Singh et al. (2017) identified a homozygous missense mutation in the TRIM36 gene (P508T; 609317.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Cellular transfection of the mutation led to disrupted microtubules, disorganized spindles, loosely arranged chromosomes, abnormal cytokinesis, decreased cell proliferation, and increased apoptosis compared to controls. Similar results were obtained by cellular knockdown of TRIM36 using siRNA. Singh et al. (2017) concluded that mutant TRIM36 adversely affects neural cell proliferation during neural tube formation, leading to anencephaly.
In a 20-week-old fetus, born of consanguineous Indian parents (family IIS-15), with anencephaly (ANPH1; 206500), Singh et al. (2017) identified a homozygous c.1522C-A transversion (c.1522C-A, NM_018700) in exon 8 of the TRIM36 gene, resulting in a pro508-to-thr (P508T) substitution at a highly conserved residue in the B30.2/SPRY domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was filtered against the dbSNP (build 135), 1000 Genomes Project, and Exome Variant Server databases. It was found at a low frequency (0.00026) in the ExAC database (September 1, 2016) among individuals of South Asian descent. In vitro studies and studies of patient cells suggested that the mutant protein was less stable than wildtype. Cellular transfection studies showed that the mutation led to disrupted microtubules, disorganized spindles, loosely arranged chromosomes, abnormal cytokinesis, decreased cell proliferation, and increased apoptosis compared to controls. Similar results were obtained by cellular knockdown of TRIM36 using siRNA.
Balint, I., Muller, A., Nagy, A., Kovacs, G. Cloning and characterisation of the RBCC728/TRIM36 zinc-binding protein from the tumor suppressor gene region at chromosome 5q22.3. Gene 332: 45-50, 2004. [PubMed: 15145053] [Full Text: https://doi.org/10.1016/j.gene.2004.02.045]
Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P. G., Ballabio, A. The tripartite motif family identifies cell compartments. EMBO J. 20: 2140-2151, 2001. [PubMed: 11331580] [Full Text: https://doi.org/10.1093/emboj/20.9.2140]
Singh, N., Kumble Bhat, V., Tiwari, a., Kodaganur, S. G., Tontanahal, S. J., Sarda, A., Malini, K. V., Kumar, A. A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family. Hum. Molec. Genet. 26: 1104-1114, 2017. [PubMed: 28087737] [Full Text: https://doi.org/10.1093/hmg/ddx020]