LRRC73

Leucine Rich Repeating Containing 73 (LRRC73) is a protein-coding gene, which, in Homo sapiens, is encoded by the LRRC73 gene.^[5].

Aliases: C6orf154, Chromosome 6 Open Reading Frame 154

Bioinformation: Accession number: NM_001012974.4 (mRNA), NP_001012992 (Protein); Genomic location: NC_000006.12: 43506968-43510346 (-)

In the human genome, LRRC73 is located on chromosome 6, specifically at 6p21.1, on the negative-sense strand. The LRRC73 sequence spans 1,782 base pairs, consisting of 6 exons^[6]. The LRRC73 gene has one protein-coding sequence^[7].

LRRC73 mRNA encodes three protein isoforms^[9]. Two of which are encoded from complete transcripts, while the remaining isoform is truncated and only carboxyl (COOH) terminus complete.

LRRC73 protein consists of 2 isoforms. Isoform one stands as the longer isoform composed of 316 amino acids. Isoform two stands as the smaller isoform and is lacking part of the 5’ coding region and has a shorter N-terminus with 193 amino acids^[10][11]. LRRC73 is a leucine-rich repeat-containing protein mostly involved in mediating protein-protein interactions^[12].

LRRC73 Isoform 1 has a theoretical molecular weight of 33 KDa and theoretical isoelectric point of 4.73^[16]. Amino acid composition analysis indicates the human LRRC73 protein to have lower-than-normal levels of phenylalanine, lysine, tyrosine, and higher-than-normal levels of leucine^[17]. LRRC73 exhibited a highly hydrophobic core (LVIFM 28%-32%), a localized negative charge cluster from residues 245 to 274 which consists of 11 acidic residues within a 30-residue window, along with an absence of transmembrane regions.

Motifscan predicted seven LRRC73 protein motifs through NCBI-CDD. Most of these motifs correspond to leucine-rich repeat (LRR) families^[18]. The most significant matches, based on E-values, include the RAN GTPase-activating protein, as well as, LRR_RI and generic LRR motifs from residues spanning from 5-255.

No transmembrane helices, catalytic signatures, linear motifs, or phosphorylation were found. The remaining three motifs for LRRC73 consist of E-values above significant thresholds and were therefore not further interpreted.

LRRC73 is situated in a genomic locus alongslide yip1 domain family member 3 (YIPF3) upstream and tight junction associated protein 1 (TJAP1) downstream^[19].

• ANKRD13D (Ankyrin repeat domain-containing protein 13D)
• TEPSIN (AP-4 complex accessory subunit Tepsin)
• VSIG10 (V-set and immunoglobulin domain containing 10)
• DOCK3 (Dedicator of cytokinesis protein 3)
• TBC1D5 (TBC1 domain family member 5)
• NPRL2 (GATOR complex protein NPRL2)
• POLR3H (DNA-directed RNA polymerase III subunit RPC8)
• OR10A4 (Olfactory receptor 10A4)
• VPS26B (Vacuolar protein sorting-associated protein 26B)
• VPS35 (Vacuolar protein sorting-associated protein 35)

LRRC73 is predicted to be located intracellularly, the protein is sublocalized to the cytosol and nuclear bodies^[24]. Expression patterns include ciliary rootlets of glandular cells within the fallopian tube, respiratory epithelia, and the nuclei of cells in seminiferous ducts.

LRRC73 showed little to no expression across most human tissues in the body. The highest expression levels have been observed in the adrenal gland, brain, and testis. RNA sequencing of total RNA from 20 human tissues showed mean expression of approximately 0.401 RPKM in the adrenal gland and 0.662 RPKM in the brain. HPA RNA-seq normal tissues showed mean expression levels of 12.679 ± 5.142 RPKM in the testis^[25].

Protein abundance data from PaxDB indicated low protein expression of LRRC73 in testis, with an abundance of approximately 0.33 parts per million (ppm), ranking 10199 out of 15744^[26].

Twenty orthologs of the LRRC73 protein were identified across various taxa, including mammals (97%-99%), birds (79%-85%), reptiles and amphibians (67%-79%), fish (69%-72%), and cartilaginous fish (61%-73%). Sequence identity data were derived using of NCBI’s BLAST, EMBOSS NEEDLE, and Timetree^{[27],[28],[29]}.

LRRC73 is seen to have no paralogs^[30][31]

The comparative LRRC73 evolutionary scatter plot illustrates the relationship between corrected percent divergence (m) and estimated date of divergence (million years ago) between the LRRC73 protein, fibrinogen alpha, and cytochrome c. Evolutionary rate comparisons place LRRC73 at an intermediate pace in comparsion to the highly conserved cytochrome c and rapidly evolving fibrinogen alpha chain.

LRRC73 belongs to the leucine rich repeat containing (LRR) family, whose members share the conserved LRR domains^[32]. Orthologs of LRRC73 have been identified in vertebrate species and not in any invertebrates, with the first appearance found approximately between 400 and 500 million years ago in cartilaginous fishes^[33].

Genome-wide association studies (GWAS) have identified 95% credible sets that prioritize LRRC73 as a likely gene associated with placenta praevia^[34]. According to GeneCards, LRRC73 has also been reported to show an association with human cytomegalovirus (HCMV) infection, however, the clinical significance of this association has not been established.