HNRNPA1 gene consists of 13 exons and 12 introns. The gene maps to 12q13.13 and is 6399 bps long (NCBI Reference Sequence: NC_000012.12: 54280690-54287088). Highlighted in red is the protein coding sequence from exons 1-10. (Figure 2)

The HNRNPA1 gene is 6399 bases long and is on the plus strand. HNRNPA1 gene has 13 exons (Jean-Philippe et al., 2013).

HNRNPA1 produces two coding transcripts (Exon 1-11). The difference between these coding transcripts is the presence or absence of exon 8 (only longer mRNA contains exon 8). A third one was reported as a potential non-coding transcript (Mendell et al, 2004). This non-coding RNA transcript has exons 12 and 13, and it does not contain exon 8.

There are 75 pseudogenes of HNRNPA1 which are: HNRNPA1P1, HNRNPA1P10, HNRNPA1P11, HNRNPA1P12, HNRNPA1P13, HNRNPA1P14, HNRNPA1P15, HNRNPA1P16, HNRNPA1P17, HNRNPA1P18, HNRNPA1P19, HNRNPA1P2, HNRNPA1P20, HNRNPA1P21, HNRNPA1P22, HNRNPA1P23, HNRNPA1P24, HNRNPA1P25, HNRNPA1P26, HNRNPA1P27, HNRNPA1P28, HNRNPA1P29, HNRNPA1P3, HNRNPA1P30, HNRNPA1P31, HNRNPA1P32, HNRNPA1P33, HNRNPA1P35, HNRNPA1P36, HNRNPA1P37, HNRNPA1P38, HNRNPA1P39, HNRNPA1P4, HNRNPA1P40, HNRNPA1P42, HNRNPA1P43, HNRNPA1P44, HNRNPA1P45, HNRNPA1P46, HNRNPA1P47, HNRNPA1P48, HNRNPA1P49, HNRNPA1P5, HNRNPA1P50, HNRNPA1P51, HNRNPA1P52, HNRNPA1P53, HNRNPA1P54, HNRNPA1P55, HNRNPA1P56, HNRNPA1P58, HNRNPA1P59, HNRNPA1P6, HNRNPA1P60, HNRNPA1P61, HNRNPA1P62, HNRNPA1P63, HNRNPA1P64, HNRNPA1P65, HNRNPA1P66, HNRNPA1P67, HNRNPA1P68, HNRNPA1P69, HNRNPA1P7, HNRNPA1P70, HNRNPA1P71, HNRNPA1P72, HNRNPA1P74, HNRNPA1P75, HNRNPA1P76, HNRNPA1P77, HNRNPA1P8, HNRNPA1P9, LOC100421349 and LOC100421402(NCBI,2018).

HNRNPA1 gene encodes a 372 amino acid protein. The protein is a member of heterogeneous nuclear ribonucleoproteins (hnRNPs) and has an estimated molecular weight of 38-39 kDa (Jean-Philippe, Paz, & Caputi, 2013).

HNRNPA1 has two RNA recognition motifs; RRM1 and RRM2. These domains are known for binding to single-stranded RNAs (Dreyfuss, Swanson, & Piñol-Roma, 1988). HNRNPA1 also possesses a prion-like domain (PLD). This domain is reported in RNA binding proteins that have been associated with neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (Kim et al., 2013). In addition, glycine-rich region mediates subcellular localization and protein-protein interactions (Han, Tang, & Smith, 2010).

HNRNPA1 mRNA is expressed in all human tissues including brain, skin, lung, breast and kidney (The Human Protein Atlas, 2018).

HNRNPA1 protein is mainly nuclear; however, under certain conditions the protein is also present in the cytosol (Roy et al., 2014). In fact, HNRNPA1 may shuttle between nucleus and cytoplasm along with mRNAs (Jønson et al., 2007).

HNRNPA1 has a very broad range of reported functions including transcriptional regulation, alternative splicing, mRNA transport, translation and miRNA processing. Most surprisingly, HNRNPA1 can interact with certain promoters and induce transcriptional repression or activation of target genes. VDR (Vitamin D receptor) (H. Chen, Hewison, Hu, & Adams, 2003), FGG (γ-fibrinogen) (Xia, 2005) and TK1 (thymidine kinase) (Lau et al., 2000) promoters are transcriptionally repressed while APOE promoter is activated by HNRNPA1 (Campillos et al., 2003).
HNRNPA1 has an important role in mRNA splicing. The protein modulates alternative splicing of various genes including INSR (Insulin Receptor) (Talukdar et al., 2011), BRCA1 (Breast Cancer 1) (Goina, Skoko, & Pagani, 2008), PKM (Pyruvate Kinase M1/2) (David, Chen, Assanah, Canoll, & Manley, 2010) and its own HNRNPA1 mRNA (Hutchison, LeBel, Blanchette, & Chabot, 2002). mRNA splicing is modulated by HNRNPA1 by exon skipping and splice site repression (Jean-Philippe et al., 2013).
HNRNPA1 contributes to telomere regulation by promoting telomerase activity via binding to telomeric sequences, potentially as an auxiliary factor for the telomerase enzyme (Zhang, Manche, Xu, & Krainer, 2006).
HNRNPA1 has roles in mRNA transport between nucleus and cytoplasm. Although the exact mechanism is unknown, HNRNPA1 binds to poly(A) tailed mRNAs both in the nucleus and cytoplasm (Mili, Shu, Zhao, & Pinol-Roma, 2001), and possibly aid their transfer through nuclear pores (Piñol-Roma & Dreyfuss, 1992).
Another function attributed to HNRNPA1 is during translation. HNRNPA1 binds to internal ribosomal entry sites (IRES) that initiates 5 cap-independent translation of certain cellular and viral mRNAs (such as, MYC), CSDE1 (Upstream of NRAS), CCND1 (Cyclin D1), VEGFA (Vascular Endothelial Growth Factor), FGF2 (Fibroblast Growth Factor), APAF1, and XIAP mRNAs (Cammas et al. 2007). In addition, the HIV-1 IRES is stimulated by hnRNPA1 (Martènez-Salas, Piñeiro, & Fernández, 2012).
In addition to mRNA processing and transport , HNRNPA1 interacts directly and specifically with C-terminal region of NF-kB alpha inhibitory subunit via its RNA-binding domain (between residues 95 and 207) resulting in the activation of nuclear factor k B (Hay, Kemp, Dargemont, & Hay, 2001). The exact mechanism of HNRNPA1 and NF-kB interaction is not completely understood. However, in cells lacking HNRNPA1, activation of NF-kB is defected. When HNRNPA1 loss is rescued, an effective NF-kB response to signal induction is observed only upon ligand induction.
As for the microRNA processing, HNRNPA1 binds to the terminal loop of pri-miR-18a, and facilitates MIR18A production by creating favorable cleavage site for DROSHA (Guil & Cáceres, 2007). In contrast, HNRNPA1 negatively affects MIRNLET7A1 (let-7a) biogenesis. HNRNPA1 binds to terminal loop of pri-let-7a-1 and interferes with the binding of KHSRP (component of both Drosha and Dicer complexes, known to promote let-7a biogenesis); hence, inhibiting processing of pri-let-7a by Drosha (Michlewski & Cáceres, 2010).

HNRNPA1 gene has homologs across Amniota including P. troglodytes, M. mulatta, B. taurus, R. norvegicus, G. gallus, M. musculus and H. sapiens (NCBI HomoloGene, 2018). There is also a well-studied HNRNPA1 homolog in D. melanogaster called Hrp36 (Singh & Lakhotia, 2012). In total, there are 97 species including invertebrates that have genes orthologous to A1 (NCBI Ensembl, 2018).

Up to 106 substitution mutations were reported in the HNRNPA1 gene in 42,067 cancer patients. Reported mutations are generally missense mutations (70 of 106). There are also 4 nonsense mutations, 30 synonymous substitutions and 2 frameshift deletions (COSMIC database, 2018). One of the frameshift deletions found in cancer patients is discovered in the Sanger Institute Cancer Genome Project (study ID :COSU652) while the other is discovered in 619 incident colorectal cancer patients in the study conducted by Giannakis et al(2016).
Yu et al. (2018) also reported a recessive frameshift mutation in HNRNPA1 leading to deregulation of cardiac transcription network and multiple signaling pathways, including Bone Morphogenetic Protein, Notch and Fibroblast growth factor signaling.