Alternative titles; symbols
HGNC Approved Gene Symbol: TRIM44
Cytogenetic location: 11p13 Genomic coordinates (GRCh38) : 11:35,662,775-35,818,007 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11p13 | ?Aniridia 3 | 617142 | Autosomal dominant | 3 |
TRIM44 belongs to the tripartite motif-containing (TRIM) protein family and functions as a negative regulator of PAX6 (607108) expression (Zhang et al., 2015).
By searching for genes in a region of chromosome 11 associated with WAGR syndrome (194072), Gawin et al. (1999) identified and cloned 2 cDNAs for TRIM44, which they designated clones 136759 and 50813. Northern blot analysis of several human tissues detected a 6-kb transcript in all tissues examined. In mouse, expression was strong in adult brain and during embryonic development after embryonic day 11.
Boutou et al. (2001) cloned Trim44, which they designated Mc7, from a mouse brain cDNA library. The deduced 345-amino acid protein has a calculated molecular mass of 38 kD. However, in vitro translation resulted in protein products with apparent molecular masses of 18 and 27 kD. Examination of the transcript suggested that these proteins were translated from alternative start codons. The full-length protein contains an N-terminal ubiquitin hydrolase (see USP39, 611594)-type zinc-finger domain, followed by a coiled-coil domain, a zinc-finger B-box homology domain, and a second coiled-coil domain near the C terminus. Mc7 also contains several potential sites for phosphorylation and N-myristoylation, single putative sites for glycosaminoglycan attachment and N-glycosylation, and several PEST motifs. Northern blot analysis detected prominent Mc7 expression in adult mouse cerebellum, and also in cerebral hemispheres and embryonic mouse brain. Little expression was detected in kidney, lung, and spleen, and none was detected in liver, intestine, or heart. In situ hybridization of cerebellar cortex demonstrated Mc7 expression at postnatal day 5 mainly in neuroblasts of the external granular layer and in developing neurons of the internal granular layer. Mc7 was also found in Purkinje cells, becoming particularly pronounced at postnatal day 10 during arborization of their dendritic tree. In the adult mouse cerebellar cortex, expression was mainly confined to Purkinje cells and to a lesser extent in granule neurons. Southern blot analysis detected MC7 orthologs in rat, pig, and human genomes.
By analysis of a PAC contig covering chromosome 11p14.1-p13, Gawin et al. (1999) mapped the TRIM44 gene to chromosome 11p13, centromeric to the FJX1 gene (612206) and telomeric to the TRAF6 gene (602355).
In a 4-generation Chinese family with aniridia mapping to chromosome 11p13 (AN3; 617142), Zhang et al. (2015) identified a heterozygous missense mutation in the TRIM44 gene (G155R; 612298.0001) that segregated with disease in the family and was not found in the ExAC database. Functional analysis demonstrated that TRIM44 is a negative regulator that restricts expression of PAX6, and that the G155R mutation significantly enhances its activity and further decreases PAX6 expression to a very low level.
In 7 affected members of a Chinese family with aniridia (AN3; 617142), Zhang et al. (2015) identified heterozygosity for a c.463G-A transition (c.463G-A, NM_017583.4) in exon 1 of the TRIM44 gene, resulting in a gly155-to-arg (G155R) substitution at a conserved residue between the ZF UBP and B-box domains. The mutation segregated fully with disease in the family and was not found in the ExAC database. Functional analysis in HLE-B3 cells demonstrated that the G155R variant significantly increases TRIM44 suppression of PAX6 (607108) expression compared to wildtype.
Boutou, E., Matsas, R., Mamalaki, A. Isolation of a mouse brain cDNA expressed in developing neuroblasts and mature neurons. Molec. Brain Res. 86: 153-167, 2001. [PubMed: 11165382] [Full Text: https://doi.org/10.1016/s0169-328x(00)00281-3]
Gawin, B., Niederfuhr, A., Schumacher, N., Hummerich, H., Little, P. F. R., Gessler, M. A 7.5 Mb sequence-ready PAC contig and gene expression map of human chromosome 11p13-p14.1. Genome Res. 9: 1074-1086, 1999. [PubMed: 10568747] [Full Text: https://doi.org/10.1101/gr.9.11.1074]
Zhang, X., Qin, G., Chen, G., Li, T., Gao, L., Huang, L., Zhang, Y., Ouyang, K., Wang, Y., Pang, Y., Zeng, B., Yu, L. Variants in TRIM44 cause aniridia by impairing PAX6 expression. Hum. Mutat. 36: 1164-1167, 2015. [PubMed: 26394807] [Full Text: https://doi.org/10.1002/humu.22907]