Chromosome 9 open reading frame 43

C9orf43 has three known complete isoforms and four partial isoforms.^[11] Isoform X1 with accession number NP_001265558.1 is the isoform discussed in this entry and contains 461 amino acids and 16 exons.^[9] Isoform X1 has a predicted molecular weight of 52.2kD and a predicted isoelectric point of 8.037.^[19][20] Isoform X1 protein abundance is predicted to be normal with normal expression.^[21]

Composition analysis of C9orf43 showed an above average frequency of Glutamine while all other amino acids were in the normal range for human proteins.^[23] DUF4647, a domain of unknown function, is present from amino acid 1-454.^[24] Globular domains are predicted from amino acid 193-361 and 375-461.^[25] C9orf43 secondary structure is predicted to be 36% alpha helical and 3% beta sheet with 73% disordered.^[26] Secondary structure predictions are conserved in orthologous proteins.

C9orf43 has no known paralogs but has orthologs ranging from mammalian orders to reptile Crocodylus porosus.^[22][27] No orthologs have been found in invertebrate or plant species. C9orf43 divergence is moderate based on the molecular clock hypothesis.^[22] C9orf43 is seen to diverge more quickly than cytochrome c but slower than fast evolving fibrinopeptides. A table of orthologous proteins constructed using BLAST contains a small subset of orthologs to exhibit the diversity of C9orf43.^[27]

Genus and species[27]	Common name	Taxonomy	Accession number[27]	Date of Divergence[22]	Percent identity[27]
Aotus Nancymaae	Ma's night monkey	Primates	XP_009186498.1	42.6	79%
Pteropus alecto	Black flying fox	Chordata	XP_015448812.1	94	62%
Bos taurus	Cow	Cerartiodactyla	XP_01532817.9	94	57%
Erinaceus europaeus	European Hedgehog	Soricomorpha	XP_007526825.1	94	54%
Phascolarctos cinereus	Koala	Diprotodontia	XP_020821154.1	159	44%
Ursus maritimus	Polar Bear	Carnivora	XP_008706212.1	94	43%
Monodelphis domestica	Gray short-tailed opossum	Didelphimorphia	XP_007475046.1	160	41%
Sarcophilus harisii	Tasmanian Devil	Dasyuromorphia	XP_003757404.3	160	32%
Crocodylus porosis	Saltwater Crocodyle	Reptilia	XP_019396109.1	312	30%

SUMOylation, O-linked glycosylation, N-acetylgluocose addition, and phosphorylation are predicted post translational modifications of C9orf43.^[28]

C9orf43 is predicted to be intracellular with a nuclear localization signal that is conserved across orthologs.^[25] The protein does not contain signal peptides or mitochondrial targeting signals indicating the protein is not predicted to be secreted or targeted to the mitochondria.^[29]

Predicted C9orf43 interaction with OR7D2 and OR4X2 olfactory receptors is likely as olfactory associated zinc finger protein is predicted to bind to the C9orf43 upstream promoter.^[30] Predicted interaction of C9orf43 with CATSPER3, a sperm associated voltage gated calcium channel, is also likely as C9orf43 is highly expressed in sperm.^[31]

C9orf43 has no known disease associations, however the polyglutamine repeat region is similar to genetic precursors in trinucleotide repeat disorders.^[32] An increase in the length of the polyglutamine repeat region is seen in diseases such as Huntington's disease and Spinocerebellar ataxia.