Alternative titles; symbols
HGNC Approved Gene Symbol: ARVCF
Cytogenetic location: 22q11.21 Genomic coordinates (GRCh38): 22:19,965,134-20,016,823 (from NCBI)
To identify genes in chromosome 22q11 that may contribute to the phenotype of velocardiofacial syndrome (VCFS; 192430), Sirotkin et al. (1997) used cDNA selection and cDNA library screening to clone the full-length human ARVCF cDNA. ARVCF encodes a 962-amino acid protein that contains 2 motifs involved in protein-protein interactions: a coiled-coil domain near the N terminus and 10 tandem armadillo repeats in the central region. Comparison of the ARVCF sequence with protein databases showed that the structure of ARVCF is most closely related to the catenin family. Members of this family play important roles in the formation of adherens junction complexes. These data suggest that ARVCF is involved in protein-protein interactions at adherens junctions. Unlike other catenin family members, ARVCF contains a nuclear localization signal (NLS), suggesting that ARVCF functions as a nuclear protein. Northern blotting showed that ARVCF is ubiquitously expressed as a 4.0- to 4.3-kb transcript in fetal and adult tissues, and Southern blotting revealed that ARVCF is conserved in vertebrates and Drosophila.
Sirotkin et al. (1997) mapped the ARVCF gene to chromosome 22 by fluorescence in situ hybridization and to chromosome 22q11 using physical mapping methods. ARVCF is located within the region of 22q11 that is hemizygous in all VCFS/DGS patients who have interstitial deletions. Based on the physical location and potential functions of ARVCF, Sirotkin et al. (1997) suggested that hemizygosity of ARVCF plays a role in the etiology of some of the phenotypes associated with VCFS.
By FISH and analysis of a somatic cell hybrid mapping panel, Bonne et al. (1998) confirmed the mapping of the ARVCF gene to chromosome 22q11.
For discussion of a possible association between variation in the ARVCF gene and anorexia nervosa, see 606788.
Duplications of human chromosome 22q11.2 (608363) are associated with elevated rates of mental retardation, autism, and many other behavioral phenotypes. Suzuki et al. (2009) determined the developmental impact of overexpression of a 190-kb segment of human 22q11.2, which includes the genes TXNRD2 (606448), COMT (116790), and ARVCF, on behaviors in bacterial artificial chromosome (BAC) transgenic mice. BAC transgenic mice and wildtype mice were tested for their cognitive capacities, affect- and stress-related behaviors, and motor activity at 1 and 2 months of age. BAC transgenic mice approached a rewarded goal faster (i.e., incentive learning), but were impaired in delayed rewarded alternation during development. In contrast, BAC transgenic and wildtype mice were indistinguishable in rewarded alternation without delays, spontaneous alternation, prepulse inhibition, social interaction, anxiety-, stress-, and fear-related behaviors, and motor activity. Compared with wildtype mice, BAC transgenic mice had a 2-fold higher level of COMT activity in the prefrontal cortex, striatum, and hippocampus. Suzuki et al. (2009) suggested that overexpression of this 22q11.2 segment may enhance incentive learning and impair the prolonged maintenance of working memory, but has no apparent affect on working memory per se, affect- and stress-related behaviors, or motor capacity. High copy numbers of this 22q11.2 segment may contribute to a highly selective set of phenotypes in learning and cognition during development.
Bonne, S., van Hengel, J., van Roy, F. Chromosomal mapping of human armadillo genes belonging to the p120(ctn)/plakophilin subfamily. Genomics 51: 452-454, 1998. [PubMed: 9721216] [Full Text: https://doi.org/10.1006/geno.1998.5398]
Sirotkin, H., O'Donnell, H., DasGupta, R., Halford, S., St. Jore, B., Puech, A., Parimoo, S., Morrow, B., Skoultchi, A., Weissman, S. M., Scambler, P., Kucherlapati, R. Identification of a new human catenin gene family member (ARVCF) from the region deleted in velo-cardio-facial syndrome. Genomics 41: 75-83, 1997. [PubMed: 9126485] [Full Text: https://doi.org/10.1006/geno.1997.4627]
Suzuki, G., Harper, K. M., Hiramoto, T., Funke, B., Lee, M., Kang, G., Buell, M., Geyer, M. A., Kucherlapati, R., Morrow, B., Mannisto, P. T., Agatsuma, S., Hiroi, N. Over-expression of a human chromosome 22q11.2 segment including TXNRD2, COMT and ARVCF developmentally affects incentive learning and working memory in mice. Hum. Molec. Genet. 18: 3914-3925, 2009. [PubMed: 19617637] [Full Text: https://doi.org/10.1093/hmg/ddp334]