LRRC73

LRRC73

LRRC73
Identifiers
AliasesLRRC73, C6orf154, leucine rich repeat containing 73
External IDsMGI: 2684934; GeneCards: LRRC73
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

221424

224813

Ensembl

ENSG00000204052

ENSMUSG00000071073

UniProt

Q5JTD7

B2RWC4

RefSeq (mRNA)

NM_001271882
NM_001012974

NM_001111142

RefSeq (protein)

NP_001012992
NP_001258811

NP_001104612

Location (UCSC)Chr 6: 43.51 – 43.51 MbChr 17: 46.56 – 46.57 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 (-)

Gene

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].

Location of LRRC73 on the P-arm of Chromosome 6
Location of LRRC73 on the P-arm of Chromosome 6[8]

mRNA

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.

Alternate Isoforms
Isoform Variant Accession # Length (nt) Exons9 Protein Isoform Accession # Length (aa)
Variant 1 NM_001012974.4 1,782 1,2,3,4,5,6 1 NP_001012992.1 316
Variant 2 NM_001271882.2 1,090 1,2,3,4,5,6 2 NP_001258811.1 193

Protein

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].

Predicted tertiary structure of LRRC73 protein. Image adopted and modified from Alpha-Fold[13].

Composition

Predicted tertiary structure of LRRC73 from I-Tasser with the localized negative charge cluster highlighted with iCn3D[14][15].

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.

Motifs and modification sites

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.

Motifs for human protein LRRC73 isoform 1
NCBI-CDD Position Description E-value
444072 28..254 COG5238, RNA1, Ran GTPase-activating protein (RanGAP) involved in mRNA processing and transport [Translation, ribosomal structure and biogenesis]. 7.00E-20
238064 5..255 cd00116, LRR_RI, Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. 1.00E-16
443914 49..243 COG4886, LRR, Leucine-rich repeat (LRR) protein [Transcription]. 2.00E-06
275380 50..243 sd00033, LRR_RI, leucine-rich repeats, ribonuclease inhibitor (RI)-like subfamily. 1.00E-04
236849 158..223 PRK11109, PRK11109, fused PTS fructose transporter subunit IIA/HPr protein. 0.14
215382 188..227 PLN02712, PLN02712, arogenate dehydrogenase. 0.57
275378 139..243 sd00031, LRR_1, leucine-rich repeats. 0.86

Protein interactions

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

Human proteins

Source:[20]

  • 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)

Conceptual translation

Sources:[21][22][23]

Conceptual translation of Leucine rich repeat 73
Conceptual translation of orthologs
Conceptual translation of orthologs
Conceptual translation of Leucine rich repeat 73
Conceptual translation of orthologs
Conceptual translation of orthologs
Conceptual translation of orthologs
Key for Homo sapiens LRRC73 conceptual translation.

Tissue localization and expression

Localization

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.

Expression

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].

Homology

Orthologs

LRRC73 Orthologs and Related Properties
Genus and Species Common Name Taxonomic Group Date of Divergence from the Human Lineage (MYA) Accession Number Sequence Length (aa) Sequence Identity to Human Protein Sequence Similarity to Human Protein
Mammalia Homo sapiens Humans Primates 0 MYA NP_001012992.1 316 100% 100%
Mus musculus House Mouse Rodentia 87 MYA NP_001104612.1 316 98.73% 99.10%
Balaenoptera acutorostrata Minke whale Artiodactyla 94 MYA XP_007193842.1 316 99.68% 99.70%
Chrysochloris asiatica Cape golden mole Afrosoricida 99 MYA XP_006860555.1 316 97.15% 99.10%
Birds Oenanthe melanoleuca Eastern black-eared wheatear Passeriformes 319 MYA XP_056342448.1 313 85.88% 80.60%
Struthio camelus African ostrich Struthioniformes 319 MYA XP_009684978.2 303 80.06% 88.00%
Numenius arquata Eurasian curlew Charadriiformes 319 MYA XP_074025247.1 318 79.13% 88.20%
Pezoporus wallicus Ground Parrot Psittaciformes 319 MYA XP_057271434.1 303 79.11% 88.30%
Reptilia Emydura macquarii macquarii Murray River turtle Testudines 319 MYA XP_067420797.1 303 79.43% 87.00%
Gopherus flavomarginatus Mexican gopher tortoise Testudines 319 MYA XP_050807631.1 303 79.43% 86.80%
Carettochelys insculpta Pitted-shelled turtle Testudines 319 MYA XP_074845841.1 303 79.11% 87.70%
Pelodiscus sinensis Chinese soft-shelled turtle Testudines 319 MYA XP_075781124.1 308 78.50% 86.90%
Amphibia Eleutherodactylus coqui Common coquí Anura 352 MYA XP_066450569.1 304 69.94% 81.00%
Bufo bufo Common toad Anura 352 MYA XP_040283598.1 304 69.06% 80.00%
Pseudophryne corroboree Corroboree frog Anura 352 MYA XP_063774856.1 302 68.04% 81.30%
Pelobates fuscus Common spadefoot toad Anura 352 MYA XP_063300254.1 302 67.72% 75.43%
Fish Silurus meridionalis Chinese large-mouth catfish Siluriformes 429 MYA XP_046731911.1 326 72.78% 81.80%
Brienomyrus brachyistius Baby Whale Osteoglossiformes 429 MYA XP_048865752.1 328 69.44% 79.50%
Cartilaginous fish Hemitrygon akajei Red stingray Myliobatiformes 462 MYA XP_072912304.1 305 73.10% 84.20%
Callorhinchus milii Elephant shark Chondrichthyes 462 MYA XP_007896433.1 263 61.08% 69.30%

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]

Evolutionary divergence

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 comparison to the highly conserved cytochrome c and rapidly evolving fibrinogen alpha chain.

The evolutionary rate of LRRC73, fibrinogen alpha chain, and cytochrome C.

Evolution

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].

Figure 3: Unrooted phylogenetic tree displaying LRRC73 ancestry
Unrooted phylogenetic tree displaying LRRC73 ancestry.

Clinical significance

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.

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000204052 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000071073 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "LRRC73 leucine rich repeat containing 73 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-03.
  6. ^ "Homo sapiens leucine rich repeat containing 73 (LRRC73), transcript variant 1, mRNA". 2025-05-01.
  7. ^ "LRRC73 leucine rich repeat containing 73 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-13.
  8. ^ GeneCards Human Gene Database. "LRRC73 Gene - GeneCards | LRC73 Protein | LRC73 Antibody". www.genecards.org. Archived from the original on 2025-08-18. Retrieved 2025-12-13.
  9. ^ "AceView: Gene:C6orf154, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2025-12-13.
  10. ^ "LRRC73 leucine rich repeat containing 73 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-13.
  11. ^ "leucine-rich repeat-containing protein 73 isoform 2 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-13.
  12. ^ "LRRC73 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2025-12-13.
  13. ^ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Retrieved 2025-12-13.
  14. ^ "I-TASSER results". aideepmed.com. Retrieved 2025-12-14.
  15. ^ "iCn3D: Web-based 3D Structure Viewer". www.ncbi.nlm.nih.gov. Retrieved 2025-12-14.
  16. ^ "Expasy - Compute pI/Mw tool". web.expasy.org. Retrieved 2025-12-13.
  17. ^ EMBL-EBI, Bioinformatics Institute. "Job Dispatcher homepage | EMBL-EBI". www.ebi.ac.uk. Retrieved 2025-12-13.
  18. ^ "Error". www.genome.jp. Retrieved 2025-12-14.
  19. ^ "LRRC73 leucine rich repeat containing 73 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-14.
  20. ^ "LRRC73 protein (human) - STRING interaction network". string-db.org. Retrieved 2025-12-13.
  21. ^ "Dotlet JS". dotlet.vital-it.ch. Retrieved 2025-12-14.
  22. ^ "DictyOGlyc 1.1 - DTU Health Tech - Bioinformatic Services". services.healthtech.dtu.dk. Retrieved 2025-12-14.
  23. ^ "NetPhos 3.1 - DTU Health Tech - Bioinformatic Services". services.healthtech.dtu.dk. Retrieved 2025-12-14.
  24. ^ "LRRC73 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2025-12-13.
  25. ^ "LRRC73 leucine rich repeat containing 73 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-14.
  26. ^ "PaxDb: Protein Abundance Database". pax-db.org. Retrieved 2025-12-14.
  27. ^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2025-12-14.
  28. ^ EMBL-EBI, Institute EB. "Job Dispatcher homepage | EMBL-EBI". www.ebi.ac.uk. Retrieved 2025-12-14.
  29. ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2025-12-14.
  30. ^ "LRRC73 leucine rich repeat containing 73 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-14.
  31. ^ "Alliance of Genome Resources". www.alliancegenome.org. Retrieved 2025-12-14.
  32. ^ Zhiqi H, Tingyi W, Dongdong C, Lan S, Guangheng Z, Qian Q, et al. (2025-01-01). "Leucine-Rich Repeat Protein Family Regulates Stress Tolerance and Development in Plants". Rice Science. 32 (1): 32–43. Bibcode:2025RisSc..32...32Z. doi:10.1016/j.rsci.2024.12.003. ISSN 1672-6308.
  33. ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2025-12-14.
  34. ^ "E2G". e2g.stanford.edu. Retrieved 2025-12-14.

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