HNRNPA2B1

Summary

HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1, HGNC:5033) is a protein-coding gene on chromosome 7p15.2, encoding Heterogeneous nuclear ribonucleoproteins A2/B1 (P22626). Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. It is a selective cancer dependency (DepMap: 31.1% of cell lines).

This gene belongs to the A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs. This gene has been described to generate two alternatively spliced transcript variants which encode different isoforms.

Source: NCBI Gene 3181 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 435 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 70
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 31.1% of screened cell lines
• MANE Select transcript: NM_002137

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5033
Approved symbol	HNRNPA2B1
Name	heterogeneous nuclear ribonucleoprotein A2/B1
Location	7p15.2
Locus type	gene with protein product
Status	Approved
Aliases	HNRNPA2, HNRNPB1
Ensembl gene	ENSG00000122566
Ensembl biotype	protein_coding
OMIM	600124
Entrez	3181

Gene structure

Transcript identifiers

Ensembl transcripts: 92 — 50 protein_coding, 35 nonsense_mediated_decay, 7 retained_intron

ENST00000354667, ENST00000356674, ENST00000360787, ENST00000463181, ENST00000476233, ENST00000490912, ENST00000495810, ENST00000608362, ENST00000618183, ENST00000676497, ENST00000676524, ENST00000676746, ENST00000676749, ENST00000676903, ENST00000676932, ENST00000677037, ENST00000677075, ENST00000677321, ENST00000677339, ENST00000677396, ENST00000677571, ENST00000677574, ENST00000677631, ENST00000677656, ENST00000677669, ENST00000677839, ENST00000677906, ENST00000678035, ENST00000678075, ENST00000678183, ENST00000678277, ENST00000678431, ENST00000678449, ENST00000678501, ENST00000678631, ENST00000678675, ENST00000678697, ENST00000678779, ENST00000678884, ENST00000678935, ENST00000678962, ENST00000678973, ENST00000678998, ENST00000679001, ENST00000679021, ENST00000679123, ENST00000679124, ENST00000679243, ENST00000679318, ENST00000715986, ENST00000868111, ENST00000868112, ENST00000868113, ENST00000868114, ENST00000868115, ENST00000868116, ENST00000868117, ENST00000868118, ENST00000868119, ENST00000868120, ENST00000868121, ENST00000868122, ENST00000868123, ENST00000868124, ENST00000868125, ENST00000868126, ENST00000923777, ENST00000923778, ENST00000923779, ENST00000923780, ENST00000923781, ENST00000923782, ENST00000923783, ENST00000923784, ENST00000923785, ENST00000923786, ENST00000923787, ENST00000923788, ENST00000923789, ENST00000923790, ENST00000923791, ENST00000923792, ENST00000923793, ENST00000923794, ENST00000923795, ENST00000951519, ENST00000951520, ENST00000951521, ENST00000951522, ENST00000951523, ENST00000951524, ENST00000951525

RefSeq mRNA: 2 — MANE Select: NM_002137 NM_002137, NM_031243

CCDS: CCDS43557, CCDS5397

Canonical transcript exons

ENST00000618183 — 11 exons

Exon	Start	End
ENSE00001390055	26197622	26197732
ENSE00001524804	26200572	26200746
ENSE00001550861	26189927	26192338
ENSE00003497454	26193251	26193373
ENSE00003508593	26195847	26195909
ENSE00003524988	26197315	26197461
ENSE00003536590	26196401	26196481
ENSE00003551946	26192495	26192577
ENSE00003675563	26196557	26196658
ENSE00003678449	26193575	26193694
ENSE00003688805	26196807	26197017

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 730.3475 / max 21362.0431, expressed in 1828 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83210	683.4916	1828
83211	39.3689	1807
83185	3.3068	1266
83184	1.2738	656
83183	1.1306	557
83186	0.5003	219
83213	0.3420	159
83212	0.3377	148
83182	0.2598	53
83209	0.2520	104

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	99.83	gold quality
tendon of biceps brachii	UBERON:0008188	99.80	gold quality
ventricular zone	UBERON:0003053	99.79	gold quality
medial globus pallidus	UBERON:0002477	99.73	gold quality
ganglionic eminence	UBERON:0004023	99.69	gold quality
endometrium	UBERON:0001295	99.68	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.68	gold quality
embryo	UBERON:0000922	99.67	gold quality
globus pallidus	UBERON:0001875	99.65	gold quality
pylorus	UBERON:0001166	99.60	gold quality
renal medulla	UBERON:0000362	99.57	gold quality
cardia of stomach	UBERON:0001162	99.57	gold quality
right testis	UBERON:0004534	99.57	gold quality
cortical plate	UBERON:0005343	99.57	gold quality
germinal epithelium of ovary	UBERON:0001304	99.55	gold quality
thymus	UBERON:0002370	99.54	gold quality
left testis	UBERON:0004533	99.54	gold quality
caecum	UBERON:0001153	99.53	gold quality
left ovary	UBERON:0002119	99.52	gold quality
ovary	UBERON:0000992	99.51	gold quality
right ovary	UBERON:0002118	99.51	gold quality
cerebellar hemisphere	UBERON:0002245	99.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.51	gold quality
cerebellar cortex	UBERON:0002129	99.50	gold quality
vermiform appendix	UBERON:0001154	99.49	gold quality
trabecular bone tissue	UBERON:0002483	99.48	gold quality
lymph node	UBERON:0000029	99.47	gold quality
body of uterus	UBERON:0009853	99.47	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.45	gold quality
metanephros cortex	UBERON:0010533	99.45	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	2127.89
E-HCAD-4	yes	53.26
E-CURD-112	yes	47.13
E-HCAD-10	yes	43.37
E-CURD-122	yes	28.32
E-HCAD-1	yes	19.62
E-GEOD-125970	yes	18.39
E-MTAB-10042	yes	11.68
E-MTAB-10553	yes	8.92
E-CURD-88	yes	6.12
E-HCAD-25	yes	5.03
E-MTAB-11011	no	3866.44
E-MTAB-4850	no	2984.05
E-HCAD-29	no	2924.04
E-MTAB-9435	no	2104.36

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDK5R1	Repression

Upstream regulators (CollecTRI, top): BRCA1, DEAF1, HNRNPAB, MYC

miRNA regulators (miRDB)

141 targeting HNRNPA2B1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Increased protein levels of heterogeneous nuclear ribonucleoprotein A2/B1 in fetal Down syndrome brains. (PMID:11771750)
• hnRNP A1/A2 binding sites control 5’ splice site selection in the hnRNP A1 mRNA precursor (PMID:12060656)
• Increased expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP) in pancreatic tissue from smokers and pancreatic tumor cells. (PMID:12065097)
• Synovial overexpression of HNRNPA2 in rheumatoid arthritis (RA) patients in conjunction with the presence of autoreactive Th1-like cells indicates potential involvement of HNRNPA2 in the pathogenesis of RA. (PMID:12097415)
• These data suggest that the RBDII domain of hnRNP A2 targets hnRNP A2 to the periphery of the cell in a microtubule-dependent manner. (PMID:12243756)
• Involved in mRNA processing and mRNA nucleocytoplasmic export. Sequestered in intranuclear aggregates. Oculopharyngeal muscular dystrophy intranuclear inclusions are “poly(A) RNA traps”, interfering with RNA export and causing muscle cell death. (PMID:12945950)
• hnRNP A2 acts on GLUT1 mRNA to inhibit expression of GLUT1 in a brain cancer cell line. (PMID:15147968)
• In human small airway epithelial cells, hnRNP A2 as well as B1 were expressed primarily in the nucleus excluding the nucleolus (PMID:15375589)
• Our study suggests that hnRNP B1-associated post-transcriptional regulations are preserved in the inferior temporal cortex of Alzheimer’s disease. (PMID:15567486)
• hnRNP A2 can bind the telomeric DNA repeat and the RNA component of telomerase. (PMID:15659580)
• tumor overexpressed gene mediates the association of hnRNP A2-positive granules with microtubules during transport and/or localization (PMID:15703215)
• Collagen prolyl 4-hydroxylase-alpha (I)mRNA is stabilized by interation of RNA-binding proteins hnRNP-A2/B1 with a U(16) element within the 3’-UTR (PMID:16464861)
• These results are consistent with a model where hnRNP E1 recruited to A2RE RNA granules by binding to hnRNP A2 inhibits translation of A2RE RNA during granule transport. (PMID:16775011)
• Pronounced peripheral T cell reactivity to hnRNP-A2 observed in majority of SLE patients and distinct phenotype of patient-derived CD8+ T cell clones suggest role for these T cells in pathogenesis of SLE. (PMID:16859514)
• Plays a central role in taking HIV-1 genomic RNA to and from the microtubule-organizing center. (PMID:17004321)
• Increased hnRNP A2/B1 expression is associated with non-small cell lung cancer (PMID:17067748)
• Data show that nuclear export of heterogeneous nuclear ribonucleoprotein A2 was mediated by CXCR4 and requires Cyclophilin A. (PMID:17991743)
• present an investigation of DNA methylation and histone modification marks across the HNRPA2B1-CBX3 locus in primary peripheral blood mononuclear cells to characterise the chromatin structure that underlies UCOE activity (PMID:18032920)
• The binding of the splicing factors hnRNPA1/A2 and DAZAP1 is the primary determinant of T6 BRCA1 exon 18 exclusion. (PMID:18391021)
• Detection of plasma hnRNP B1 mRNA by transcription-reverse transcription concerted reaction improves overall prognosis in lung cancer patients. (PMID:18461365)
• Neither grade nor stage of non-small cell lung carcinomas was correlated with hnRNP B1 immunreactivity (PMID:19609729)
• Alternative splicing of an exon in the 5’ untranslated region of a gene termed TP53INP2 is a key event downstream of hnRNP A2 that is necessary for cells to invade the extracellular matrix. (PMID:19934309)
• human gliomas overexpress c-Myc, PTB, hnRNPA1 and hnRNPA2 in a manner that correlates with PKM2 expression (PMID:20010808)
• splicing repressors hnRNP A1 and A2, as well as the polypyrimidine-tract-binding protein PTB, contribute to control of pyruvate kinase isoform M1 and M2 expression (PMID:20133837)
• melanoma antigen expressed in G361, a representative melanoma cell line/ reacted with autoantibodies in patient sera (PMID:20181627)
• These data suggest involvement of hnRNP-A2 specific cellular autoimmune responses in rheumatoid arthritis pathogenesis (PMID:20232340)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Increased expression and cytoplasmic localization of hnRNP A2/B1 is associated with the development of hepatocellular carcinoma. (PMID:20604928)
• A conserved nonsense-mediated mRNA decay event within HNRNPA2B1 that appears to mediate autoregulation of HNRNPA2B1 expression levels, was identified upon UPF1 knockdown . (PMID:20946641)
• hnRNP A2/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. (PMID:20978319)
• hnRNP-A2/B1 affected tumor cell differentiation through interaction with oncogenes and tumor-suppressor genes, and it was overexpressed in human gastric cancer. (PMID:21175803)
• The expression and distribution of hnRNP A2/B1 can affect the differentiation of SK-N-SH cells, as well as its co-localization with related oncogenes and tumor suppressor genes (PMID:21321999)
• The impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue, was evaluated. (PMID:21547579)
• High HNRPA2B1 expression is associated with pancreatic cancer progression. (PMID:21642356)
• Data show that hnRNPA1/A2, HuR and DAZAP1 splicing factors and DHX36 RNA helicase bind to the ISE, with hnRNPA1 acting negatively and DAZAP1 positively on splicing selection. (PMID:21858080)
• In addition to the core protein, hnRNP A2 also associated with Japanese encephalitis virus nonstructural protein 5 and with the 5’-untranslated region of the negative-sense Japanese encephalitis virus RNA. (PMID:21865391)
• Patient serum IgA was reactve against human recombinant hnRNP-A2/B1 in Behcet (83.3%), systemic lupus erythematosus (13.3%), rheumatoid arthritis (26.7%), Takayasu’s arteritis (30%), and no IgA nephropathy patients, vs healthy controls (20%). (PMID:22205302)
• The positive expression rate of hnRNPA2/B1 in small cell lung cancer was significantly higher than that in the control specimens. (PMID:22325225)
• Heterogeneous nuclear ribonucleoprotein A2/B1, an human telomerase reverse transcriptase - associated protein, is a potential prognostic biomarker for hepatocellular carcinoma patients (PMID:22372738)
• hnRNP A2/B1 protein is a regulator of HPV-16 late gene expression (PMID:22484615)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hnrnpa2b1	ENSMUSG00000004980
rattus_norvegicus	Hnrnpa2b1	ENSRNOG00000011175

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoproteins A2/B1 — P22626 (reviewed: P22626)

All UniProt accessions (11): A0A024RA28, A0A087WUI2, A0A7I2V323, A0A7I2V3P1, A0A7I2V3P7, A0A7I2V4I6, A0A7I2V4N0, A0A7I2V4N1, A0A7I2V4S4, A0A7I2YQN4, P22626

UniProt curated annotations — full annotation on UniProt →

Function. Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs. Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm. Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion. Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear ‘reader’ of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts. Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs. Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. Also plays a role in the activation of the innate immune response. Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6. In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production. (Microbial infection) Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the microtubule organizing center (MTOC), and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) sequence motifs present on HIV-1 genomic RNA, and promotes its transport.

Subunit / interactions. Homodimer; dimerization is required for nucleocytoplasmic translocation. Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with IGF2BP1. Interacts with C9orf72. Interacts with DGCR8. Interacts with TARDBP. Interacts with CKAP5. Interacts with TBK1. Interacts with STING1. Interacts with SRC. Interacts with PPIA/CYPA. Interacts (via C-terminus) with FAM76B; the interaction results in retention of HNRNPA2B1 in the nucleus and inhibition of the NF-kappa-B-mediated inflammatory pathway. Interacts with NF-kappa-B inhibitors NFKBIA and NFKBIE; the interaction may be mediated by the RRM2 domain of HNRNPA2B1, and HNRNPA2B1 may interact simultaneously with FAM76B and either NFKBIA or NFKBIE to form a complex. Interacts with CEP112.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm. Cytoplasmic granule. Secreted. Extracellular exosome Nucleus.

Post-translational modifications. Sumoylated in exosomes, promoting miRNAs-binding. Asymmetric dimethylation at Arg-266 constitutes the major methylation site. According to a report, methylation affects subcellular location and promotes nuclear localization. According to another report, methylation at Arg-266 does not influence nucleocytoplasmic shuttling.

Disease relevance. Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (IBMPFD2) [MIM:615422] An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry. Oculopharyngeal muscular dystrophy 2 (OPMD2) [MIM:620460] An autosomal dominant, early-onset myopathy characterized by progressive muscle weakness, ptosis, ophthalmoplegia, dysphagia, and variable degrees of respiratory insufficiency. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by frameshift variants that cluster in the low complexity disordered region. They abolish the native stop codon, and extend the reading frame resulting in a common C-terminal sequence. All variants escape degradation by the RNA quality control system, and mutant proteins accumulate in the cytoplasm due to impaired nucleocytoplasmic trafficking.

Domain organisation. The disordered region, when incubated at high concentration, is able to polymerize into labile, amyloid-like fibers and form cross-beta polymerization structures, probably driving the formation of hydrogels. In contrast to irreversible, pathogenic amyloids, the fibers polymerized from low complexity (LC) regions disassemble upon dilution. A number of evidence suggests that formation of cross-beta structures by LC regions mediate the formation of RNA granules, liquid-like droplets, and hydrogels.

Isoforms (2)

UniProt ID	Names	Canonical?
P22626-1	B1, hnRNP B1	yes
P22626-2	A2, hnRNP A2

RefSeq proteins (2): NP_002128, NP_112533 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR021662	HnRNPA1/A2_C	Domain
IPR034486	hnRNPA2B1_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF11627

UniProt features (114 total): modified residue 36, mutagenesis site 26, strand 17, cross-link 10, helix 9, turn 5, domain 2, region of interest 2, compositionally biased region 2, chain 1, short sequence motif 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
6WPQ	X-RAY DIFFRACTION	1.1
7WM3	X-RAY DIFFRACTION	1.62
5HO4	X-RAY DIFFRACTION	1.85
5WWG	X-RAY DIFFRACTION	2.03
5WWF	X-RAY DIFFRACTION	2.15
5WWE	X-RAY DIFFRACTION	2.4
5EN1	X-RAY DIFFRACTION	2.58
8HNI	X-RAY DIFFRACTION	2.64
6WQK	ELECTRON MICROSCOPY	3.1
8DUW	ELECTRON MICROSCOPY	3.2
8DU2	ELECTRON MICROSCOPY	3.3
8EC7	ELECTRON MICROSCOPY	3.9
1X4B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22626-F1	71.39	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (46): 29, 38, 5, 85, 104, 140, 149, 159, 168, 173, 176, 189, 201, 203, 203, 203, 212, 213, 213, 213 …

Mutagenesis-validated functional residues (26):

Position	Phenotype
207	does not affect hydrogel-binding.
209	does not affect hydrogel-binding.
219	does not affect hydrogel-binding.
227	does not affect hydrogel-binding.
228	about 10-fold increase in interferon beta production.
234	does not affect hydrogel-binding.
240	does not affect hydrogel-binding.
244	does not affect hydrogel-binding.
247	slightly affects hydrogel-binding.
256	does not affect hydrogel-binding.
262	slightly affects hydrogel-binding.
269	does not affect hydrogel-binding.
276	impairs hydrogel-binding.
283	slightly affects hydrogel-binding.
287	does not affect hydrogel-binding.
290	impairs hydrogel-binding.
295	impairs hydrogel-binding.
300	slightly affects hydrogel-binding.
303	impairs hydrogel-binding.
306	slightly affects hydrogel-binding.
313	slightly affects hydrogel-binding.
321	impairs hydrogel-binding.
331	impairs hydrogel-binding.
336	slightly affects hydrogel-binding.
347	does not affect hydrogel-binding.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-72172	mRNA Splicing
R-HSA-8953854	Metabolism of RNA
R-HSA-9020591	Interleukin-12 signaling

MSigDB gene sets: 496 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, MORF_ESPL1, MORF_SMC1L1, TGCGCANK_UNKNOWN, E2F4DP1_01, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MORF_UBE2I, MORF_RRM1, MORF_HDAC1, MORF_RAD21, MORF_CDK2, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION

GO Biological Process (11): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), mRNA export from nucleus (GO:0006406), primary miRNA processing (GO:0031053), DNA geometric change (GO:0032392), RNA transport (GO:0050658), mRNA transport (GO:0051028), positive regulation of telomere maintenance via telomere lengthening (GO:1904358), miRNA transport (GO:1990428), RNA splicing (GO:0008380), regulation of macromolecule metabolic process (GO:0060255)

GO Molecular Function (11): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), miRNA binding (GO:0035198), identical protein binding (GO:0042802), single-stranded telomeric DNA binding (GO:0043047), DNA polymerase binding (GO:0070182), G-rich strand telomeric DNA binding (GO:0098505), molecular condensate scaffold activity (GO:0140693), N6-methyladenosine-containing RNA reader activity (GO:1990247), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (12): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), Cajal body (GO:0015030), membrane (GO:0016020), nuclear matrix (GO:0016363), extracellular exosome (GO:0070062), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
Interleukin-12 signaling	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Immune System	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Processing of Capped Intron-Containing Pre-mRNA	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
RNA processing	2
RNA transport	2
binding	2
nuclear lumen	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
miRNA processing	1
DNA conformation change	1
nucleic acid transport	1
establishment of RNA localization	1
telomere maintenance via telomere lengthening	1
positive regulation of telomere maintenance	1
regulation of telomere maintenance via telomere lengthening	1
regulation of metabolic process	1
macromolecule metabolic process	1
nucleic acid binding	1
mRNA binding	1
regulatory RNA binding	1
protein binding	1
telomeric repeat DNA binding	1
sequence-specific single stranded DNA binding	1
enzyme binding	1
single-stranded telomeric DNA binding	1
protein-macromolecule adaptor activity	1
RNA binding	1
protein-RNA adaptor activity	1
chromosomal region	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
extracellular vesicle	1
Prp19 complex	1
spliceosomal complex	1

Protein interactions and networks

STRING

4491 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPA2B1	HNRNPC	P07910	993
HNRNPA2B1	DGCR8	Q8WYQ5	992
HNRNPA2B1	HNRNPL	P14866	981
HNRNPA2B1	TARDBP	Q13148	980
HNRNPA2B1	PTBP1	P26599	944
HNRNPA2B1	FUS	P35637	943
HNRNPA2B1	SLC25A15	Q9Y619	942
HNRNPA2B1	ILF3	Q12906	940
HNRNPA2B1	YTHDC1	Q96MU7	924
HNRNPA2B1	YTHDF1	Q9BYJ9	922
HNRNPA2B1	HNRNPA1	P09651	918
HNRNPA2B1	IGF2BP1	Q9NZI8	894
HNRNPA2B1	HNRNPF	P52597	893
HNRNPA2B1	FMR1	Q06787	886
HNRNPA2B1	HNRNPM	P52272	871

IntAct

393 interactions, top by confidence:

A	B	Type	Score
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
RBM45	HNRNPA1	psi-mi:“MI:0914”(association)	0.740
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HNRNPA2B1	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.670
HNRNPD	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
JMJD6	TP53	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
HNRNPL	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.630
HNRNPL	HNRNPA2B1	psi-mi:“MI:0914”(association)	0.630
HNRNPA2B1	HNRNPL	psi-mi:“MI:0407”(direct interaction)	0.630
HNRNPL	HNRNPA2B1	psi-mi:“MI:0914”(association)	0.620
HNRNPL	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.620
	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.560
	HNRNPA2B1	psi-mi:“MI:0914”(association)	0.560
ILF3	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.560
L1TD1	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA2B1	HNRNPA3	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA2B1	HNRNPK	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA2B1	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA2B1	HNRNPM	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1112): HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-RNA), HNRNPA2B1 (Affinity Capture-RNA), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Protein-peptide), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Reconstituted Complex), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), HNRNPA2B1 (Two-hybrid)

ESM2 similar proteins: A0A0D1C8Z4, A5A6H4, A7VJC2, O88569, P04256, P07909, P09651, P09867, P17130, P19198, P21522, P22626, P35637, P48810, P49312, P51968, P51989, P51990, P51991, P51992, P56959, Q01844, Q08473, Q13151, Q22037, Q28009, Q28521, Q2HJ60, Q32P51, Q43472, Q5PQ53, Q5RBU8, Q61545, Q640A2, Q641Z8, Q6DC93, Q6URK4, Q7ZX83, Q8BG05, Q8EA81

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A0A2R8Y4L2, A5A6H4, A5A6M3, A7VJC2, D4AE41, O22703, O75526, O88569, O89086, O93235, P04256, P09651, P09867, P10979, P17130, P19682, P19683, P19684, P22626, P28644, P38159, P39697, P41891, P49310, P49311, P49312, P49313, P49314, P51968, P51989, P51990, P51991, P51992, P60824, P60825, P60826, P84586, P98179

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HNRNPA2B1	“down-regulates quantity by repression”	CDK5R1	“transcriptional regulation”
MYC	“up-regulates quantity by expression”	HNRNPA2B1	“transcriptional regulation”
FUS	“down-regulates quantity by repression”	HNRNPA2B1	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 207 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	13	10.6×	7e-08
Autophagy	9	9.5×	6e-05
mRNA Polyadenylation	15	9.3×	3e-08
Processing of Capped Intron-Containing Pre-mRNA	16	9.3×	1e-08
PKR-mediated signaling	7	7.0×	6e-03
mRNA Splicing - Major Pathway	17	6.6×	2e-07
Dengue Virus-Host Interactions	17	5.5×	2e-06
Neddylation	13	4.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
random inactivation of X chromosome	5	26.4×	2e-04
mitophagy	12	21.6×	2e-10
autophagosome assembly	12	15.2×	9e-09
intrinsic apoptotic signaling pathway	7	14.2×	2e-04
autophagosome maturation	7	13.9×	2e-04
mRNA stabilization	6	12.4×	1e-03
positive regulation of protein ubiquitination	7	8.4×	2e-03
macroautophagy	6	8.2×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — HCC.

Clinical variants and AI predictions

ClinVar

435 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	104
Likely benign	263
Benign	28

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2574642	NM_002137.4(HNRNPA2B1):c.992del (p.Gly331fs)	Pathogenic
2574643	NM_002137.4(HNRNPA2B1):c.981del (p.Gly328fs)	Pathogenic
2574644	NM_002137.4(HNRNPA2B1):c.968del (p.Asn323fs)	Pathogenic
65454	NM_002137.4(HNRNPA2B1):c.869A>T (p.Asp290Val)	Pathogenic
1178344	NM_002137.4(HNRNPA2B1):c.965G>A (p.Gly322Glu)	Likely pathogenic
1501742	NM_002137.4(HNRNPA2B1):c.893C>T (p.Pro298Leu)	Likely pathogenic

SpliceAI

2001 predictions. Top by Δscore:

Variant	Effect	Δscore
7:26177940:TAG:T	acceptor_loss	1.0000
7:26177941:A:AG	acceptor_gain	1.0000
7:26177941:A:AT	acceptor_loss	1.0000
7:26177941:AG:A	acceptor_gain	1.0000
7:26177942:G:A	acceptor_loss	1.0000
7:26177942:G:GT	acceptor_gain	1.0000
7:26177942:GG:G	acceptor_gain	1.0000
7:26177942:GGA:G	acceptor_gain	1.0000
7:26177942:GGAGA:G	acceptor_gain	1.0000
7:26178118:ATGAG:A	donor_gain	1.0000
7:26178119:TGAGG:T	donor_loss	1.0000
7:26178120:GAG:G	donor_gain	1.0000
7:26178121:AGG:A	donor_loss	1.0000
7:26178123:G:GG	donor_gain	1.0000
7:26178123:GTA:G	donor_loss	1.0000
7:26178124:T:G	donor_loss	1.0000
7:26183695:CTACA:C	acceptor_loss	1.0000
7:26183696:TACA:T	acceptor_loss	1.0000
7:26183697:ACAG:A	acceptor_loss	1.0000
7:26183698:CAGAG:C	acceptor_loss	1.0000
7:26183699:A:AG	acceptor_gain	1.0000
7:26183699:A:C	acceptor_loss	1.0000
7:26183700:G:GC	acceptor_loss	1.0000
7:26183700:G:GG	acceptor_gain	1.0000
7:26183700:GA:G	acceptor_gain	1.0000
7:26183700:GAGAC:G	acceptor_gain	1.0000
7:26183780:TGGAG:T	donor_loss	1.0000
7:26183782:G:GT	donor_gain	1.0000
7:26183783:AGGT:A	donor_loss	1.0000
7:26183784:GGTA:G	donor_loss	1.0000

AlphaMissense

1743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:26196610:G:T	A187D	1.000
7:26196612:C:A	K186N	1.000
7:26196612:C:G	K186N	1.000
7:26196614:T:C	K186E	1.000
7:26196614:T:G	K186Q	1.000
7:26196626:C:G	A182P	1.000
7:26196640:A:T	I177N	1.000
7:26196647:G:C	H175D	1.000
7:26196818:T:A	D167V	1.000
7:26196818:T:C	D167G	1.000
7:26196818:T:G	D167A	1.000
7:26196819:C:A	D167Y	1.000
7:26196819:C:G	D167H	1.000
7:26196821:A:T	V166E	1.000
7:26196827:T:A	D164V	1.000
7:26196827:T:C	D164G	1.000
7:26196828:C:G	D164H	1.000
7:26196838:A:C	F160L	1.000
7:26196838:A:T	F160L	1.000
7:26196839:A:G	F160S	1.000
7:26196840:A:G	F160L	1.000
7:26196840:A:T	F160I	1.000
7:26196845:A:T	V158D	1.000
7:26196847:A:C	F157L	1.000
7:26196847:A:T	F157L	1.000
7:26196848:A:C	F157C	1.000
7:26196848:A:G	F157S	1.000
7:26196849:A:C	F157V	1.000
7:26196849:A:G	F157L	1.000
7:26196849:A:T	F157I	1.000

dbSNP variants (sampled 300 via entrez): RS1000010780 (7:26198388 C>A), RS1000217498 (7:26194767 A>G), RS1000259971 (7:26200774 C>A,G), RS1000436059 (7:26196000 A>C,G), RS1000593306 (7:26191835 A>G), RS1000825955 (7:26195488 T>A), RS1000830022 (7:26199048 T>C), RS1000882442 (7:26199148 T>G), RS1000987846 (7:26194747 A>C), RS1001060475 (7:26191237 TTAAG>T), RS1001174655 (7:26195349 A>G), RS1001244284 (7:26202145 A>T), RS1001333635 (7:26194852 T>C), RS1001763663 (7:26193017 A>G), RS1001828263 (7:26193457 C>G,T)

Disease associations

OMIM: gene MIM:600124 | disease phenotypes: MIM:615422, MIM:620460, MIM:609500

GenCC curated gene-disease

Disease	Classification	Inheritance
inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2	Strong	Autosomal dominant
oculopharyngeal muscular dystrophy	Strong	Autosomal dominant
oculopharyngeal muscular dystrophy 2	Strong	Autosomal dominant
amyotrophic lateral sclerosis	Moderate	Autosomal dominant
inclusion body myopathy with Paget disease of bone and frontotemporal dementia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2	Moderate	AD

Mondo (7): inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (MONDO:0014178), frontotemporal dementia (MONDO:0017276), oculopharyngeal muscular dystrophy 2 (MONDO:0958195), myopathy, autophagic vacuolar, infantile-onset (MONDO:0012286), amyotrophic lateral sclerosis (MONDO:0004976), inclusion body myopathy with Paget disease of bone and frontotemporal dementia (MONDO:0000507), oculopharyngeal muscular dystrophy (MONDO:0008116)

Orphanet (1): Frontotemporal dementia (Orphanet:282)

HPO phenotypes

70 total (30 of 70 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000602	Ophthalmoplegia
HP:0000708	Atypical behavior
HP:0000925	Abnormality of the vertebral column
HP:0001249	Intellectual disability
HP:0001270	Motor delay
HP:0001293	Cranial nerve compression
HP:0001324	Muscle weakness
HP:0001397	Hepatic steatosis
HP:0001618	Dysphonia
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0002015	Dysphagia
HP:0002093	Respiratory insufficiency
HP:0002145	Frontotemporal dementia
HP:0002300	Mutism
HP:0002380	Fasciculations
HP:0002381	Aphasia
HP:0002442	Dyscalculia
HP:0002450	Abnormal motor neuron morphology
HP:0002460	Distal muscle weakness
HP:0002463	Language impairment
HP:0002493	Upper motor neuron dysfunction
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0002659	Increased susceptibility to fractures
HP:0002683	Abnormal calvaria morphology
HP:0002756	Pathologic fracture

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005956_35	Waist-to-hip ratio adjusted for BMI	8.000000e-14
GCST005958_8	Waist-to-hip ratio adjusted for BMI (age >50)	5.000000e-07
GCST005962_19	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	8.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D057180	Frontotemporal Dementia	C10.228.140.380.266.299; C10.574.950.300.299; C18.452.845.800.300.299; F03.615.400.380.299
D039141	Muscular Dystrophy, Oculopharyngeal	C05.651.534.500.450; C10.668.491.175.500.450; C16.320.577.450

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3124741 (SINGLE PROTEIN), CHEMBL3137265 (SELECTIVITY GROUP)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.94	Kd	11.52	nM	CHEMBL5653589
7.94	ED50	11.52	nM	CHEMBL5653589
7.08	Kd	82.25	nM	CHEMBL3752910
7.08	ED50	82.25	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148525: Binding affinity to human HNRNPA2B1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0115	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148525: Binding affinity to human HNRNPA2B1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0823	uM

CTD chemical–gene interactions

102 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects expression	4
bisphenol A	affects expression, decreases expression	3
sodium arsenite	affects reaction, increases expression, decreases expression	3
Copper	increases expression, decreases expression, affects binding	3
Quercetin	increases expression, increases phosphorylation, decreases expression	3
Nanotubes, Carbon	affects expression, increases expression	3
methylmercuric chloride	increases expression	2
Decitabine	decreases expression, affects expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	affects expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization, increases expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
afimoxifene	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
triphenyltin	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118560	Binding	Binding affinity to HNRNPA2B1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2YZ	Abcam HEK293T HNRNPA2B1 KO	Transformed cell line	Female
CVCL_C9EQ	HAP1 HNRNPA2B1 (-)	Cancer cell line	Male
CVCL_D6C6	HyCyte MDA-MB-231 KO-hHNRNPA2B1	Cancer cell line	Female
CVCL_E1N0	HyCyte THP-1 KO-hHNRNPA2B1	Cancer cell line	Male
CVCL_E4QB	KOLF2.1J HNRNPA2B1 8.1kbdel DEL/WT	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

441 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00376051	PHASE4	COMPLETED	Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT06093126	PHASE4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
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