Alternative titles; symbols
HGNC Approved Gene Symbol: LRIG2
Cytogenetic location: 1p13.2 Genomic coordinates (GRCh38): 1:113,073,198-113,132,260 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p13.2 | Urofacial syndrome 2 | 615112 | Autosomal recessive | 3 |
By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1998) cloned LRIG2, which they designated KIAA0806. The deduced protein contains 1,065 amino acids. RT-PCR ELISA detected highest expression in brain and intermediate expression in all other tissues examined except spleen, which showed little to no expression.
Holmlund et al. (2004) cloned LRIG2 from a human brain cDNA library. The deduced protein contains a signal peptide; 15 tandem leucine-rich repeats with cysteine-rich N- and C-flanking domains; 3 C2-type immunoglobulin-like domains; a transmembrane domain; and a cytoplasmic tail. LRIG2 shares 47% amino acid identity with LRIG1 (608868). Northern blot analysis detected a 4.6-kb LRIG2 transcript in heart and a 4.8-kb transcript in all other tissues analyzed. Quantitative RT-PCR detected highest expression in skin and lowest expression in bladder. Western blot analysis detected LRIG2 at an apparent molecular mass of 132 kD in stomach, prostate, lung, and fetal brain, as well as in transfected COS-7 cells. N-glycosidase treatment reduced the apparent molecular mass to 107 kD. Cell surface biotinylation and confocal fluorescence laser microscopy demonstrated expression of LRIG2 both at the cell surface and in the cytoplasm of transfected COS-7 cells.
Guo et al. (2004) cloned mouse Lrig2. The deduced mouse protein shares 87.1% amino acid identity with human LRIG2. Human and mouse LRIG2 share highest conservation with LRIG1 and LRIG3 (608870) in the extracellular, transmembrane, and membrane-proximal sequences. Quantitative PCR detected ubiquitous but variable expression of human LRIG2, with highest expression in uterus and lowest expression in bladder. Quantitative PCR of several mouse tissues showed ubiquitous expression, but the pattern of expression differed from that in human tissues.
Holmlund et al. (2004) determined that the LRIG2 gene contains 19 exons and spans at least 50 kb.
By FISH, Holmlund et al. (2004) mapped the LRIG2 gene to chromosome 1p13. Guo et al. (2004) mapped the mouse Lrig2 gene to a region of chromosome 3F2+2 that shows homology of synteny to human chromosome 1p13.
In affected sibs from a consanguineous Turkish family with urofacial syndrome mapping to chromosome 1p13.2 (UFS2; 615112), Stuart et al. (2013) performed exome sequencing and identified homozygosity for a 1-bp deletion in the LRIG2 gene (608869.0001); the mutation segregated with disease in the family and was not found in variome databases, 116 local exomes, or 94 Turkish controls. In a second consanguineous Turkish UFS family, 2 affected sisters were homozygous for a nonsense mutation in LRIG2 (R709X; 608869.0002). In addition, a girl with UFS from a nonconsanguineous Spanish family was found by exome and Sanger sequencing to be compound heterozygous for a deletion and an insertion mutation in LRIG2 (608869.0003-608869.0004).
In an 8-year-old Turkish girl with urofacial syndrome (UFS2; 615112), Stuart et al. (2013) identified homozygosity for a 1-bp deletion (c.1230delA) in exon 10 of the LRIG2 gene, causing a frameshift predicted to result in premature termination (Glu140AspfsTer6). The deletion was confirmed by Sanger sequencing, and was also found in homozygosity in her asymptomatic 5-year-old brother, who exhibited only the facial features of UFS and had a normal urinary tract by ultrasound and uroflowmetry. The mutation was present in heterozygosity in the unaffected first-cousin parents and was not found in variome databases, 116 local exomes, or 94 Turkish controls.
In 2 sisters from a consanguineous Turkish family with urofacial syndrome (UFS2; 615112), Stuart et al. (2013) identified homozygosity for a c.2125C-T transition in exon 15 of the LRIG2 gene, resulting in an arg709-to-ter (R709X) substitution. The mutation was present in heterozygosity in the unaffected parents and was not found in variome databases, 116 local exomes, or 94 Turkish controls.
In a 5-year-old Spanish girl with urofacial syndrome (UFS2; 615112), Stuart et al. (2013) identified compound heterozygosity for a 1-bp deletion (c.2088delC) in exon 15 of the LRIG2 gene, causing a frameshift predicted to result in premature termination (Ser697HisfsTer11), and a 371-bp insertion (c.1980_1981ins371) in exon 14, resulting in a transcript that skips exon 14 and is not subject to nonsense-mediated decay, as determined by sequencing of lymphocyte cDNA. Her unaffected parents were each heterozygous for one of the mutations.
For discussion of the 371-bp insertion in exon 14 of the LRIG2 gene (c.1980_1981ins371) that was found in compound heterozygous state in a patient with urofacial syndrome (UFS2; 615112) by Stuart et al. (2013), see 608869.0003.
Guo, D., Holmlund, C., Henriksson, R., Hedman, H. The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in Ascidiacea. Genomics 84: 157-165, 2004. [PubMed: 15203213] [Full Text: https://doi.org/10.1016/j.ygeno.2004.01.013]
Holmlund, C., Nilsson, J., Guo, D., Starefeldt, A., Golovleva, I., Henriksson, R., Hedman, H. Characterization and tissue-specific expression of human LRIG2. Gene 332: 35-43, 2004. [PubMed: 15145052] [Full Text: https://doi.org/10.1016/j.gene.2004.02.002]
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 5: 277-286, 1998. [PubMed: 9872452] [Full Text: https://doi.org/10.1093/dnares/5.5.277]
Stuart, H. M., Roberts, N. A., Burgu, B., Daly, S. B., Urquhart, J. E., Bhaskar, S., Dickerson, J. E., Mermerkaya, M., Silay, M. S., Lewis, M. A., Olondriz, M. B. O., Gener, B., and 18 others. LRIG2 mutations cause urofacial syndrome. Am. J. Hum. Genet. 92: 259-264, 2013. [PubMed: 23313374] [Full Text: https://doi.org/10.1016/j.ajhg.2012.12.002]