HNRNPA1

Summary

HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1, HGNC:5031) is a protein-coding gene on chromosome 12q13.13, encoding Heterogeneous nuclear ribonucleoprotein A1 (P09651). Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection. It is a selective cancer dependency (DepMap: 20.1% of cell lines).

This gene encodes a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs), which are RNA-binding proteins that associate with pre-mRNAs in the nucleus and influence pre-mRNA processing, as well as other aspects of mRNA metabolism and transport. The protein encoded by this gene is one of the most abundant core proteins of hnRNP complexes and plays a key role in the regulation of alternative splicing. Mutations in this gene have been observed in individuals with amyotrophic lateral sclerosis 20. Multiple alternatively spliced transcript variants have been found. There are numerous pseudogenes of this gene distributed throughout the genome.

Source: NCBI Gene 3178 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 118 total — 4 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 113
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 20.1% of screened cell lines
• MANE Select transcript: NM_031157

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5031
Approved symbol	HNRNPA1
Name	heterogeneous nuclear ribonucleoprotein A1
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	hnRNP-A1, ALS20
Ensembl gene	ENSG00000135486
Ensembl biotype	protein_coding
OMIM	164017
Entrez	3178

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 59 protein_coding, 18 nonsense_mediated_decay, 10 protein_coding_CDS_not_defined, 6 retained_intron

ENST00000330752, ENST00000340913, ENST00000546500, ENST00000547276, ENST00000547566, ENST00000547708, ENST00000547870, ENST00000548688, ENST00000550482, ENST00000550994, ENST00000551665, ENST00000551679, ENST00000551702, ENST00000551803, ENST00000676472, ENST00000676528, ENST00000676572, ENST00000676661, ENST00000676707, ENST00000676725, ENST00000676794, ENST00000676842, ENST00000676853, ENST00000676855, ENST00000676886, ENST00000676925, ENST00000676951, ENST00000677061, ENST00000677072, ENST00000677191, ENST00000677210, ENST00000677220, ENST00000677224, ENST00000677249, ENST00000677279, ENST00000677291, ENST00000677375, ENST00000677385, ENST00000677488, ENST00000677518, ENST00000677539, ENST00000677636, ENST00000677645, ENST00000677666, ENST00000677778, ENST00000677832, ENST00000677840, ENST00000677847, ENST00000677945, ENST00000678077, ENST00000678093, ENST00000678103, ENST00000678199, ENST00000678212, ENST00000678279, ENST00000678347, ENST00000678365, ENST00000678412, ENST00000678418, ENST00000678424, ENST00000678448, ENST00000678456, ENST00000678513, ENST00000678581, ENST00000678597, ENST00000678611, ENST00000678687, ENST00000678690, ENST00000678873, ENST00000678876, ENST00000678900, ENST00000678919, ENST00000678934, ENST00000678947, ENST00000678970, ENST00000679026, ENST00000679063, ENST00000679079, ENST00000679101, ENST00000679228, ENST00000679251, ENST00000679273, ENST00000679319, ENST00000679344, ENST00000869553, ENST00000938109, ENST00000938110, ENST00000938111, ENST00000938112, ENST00000938113, ENST00000938114, ENST00000945499, ENST00000945500

RefSeq mRNA: 2 — MANE Select: NM_031157 NM_002136, NM_031157

CCDS: CCDS41793, CCDS44909

Canonical transcript exons

ENST00000340913 — 11 exons

Exon	Start	End
ENSE00000920032	54282573	54282665
ENSE00000920033	54282800	54282874
ENSE00001532273	54283812	54283967
ENSE00001690592	54283079	54283234
ENSE00002375624	54280726	54280822
ENSE00003335203	54284258	54284317
ENSE00003542256	54281386	54281502
ENSE00003578192	54282090	54282300
ENSE00003638233	54281795	54281941
ENSE00003790955	54282394	54282486
ENSE00003899085	54284549	54287087

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5687 / max 894.6417, expressed in 1803 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125890	36.0644	1801
125891	0.6361	257
125893	0.6219	309
125892	0.2463	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.97	gold quality
ventricular zone	UBERON:0003053	99.95	gold quality
embryo	UBERON:0000922	99.94	gold quality
cortical plate	UBERON:0005343	99.93	gold quality
germinal epithelium of ovary	UBERON:0001304	99.92	gold quality
parietal pleura	UBERON:0002400	99.92	gold quality
pleura	UBERON:0000977	99.91	gold quality
tibia	UBERON:0000979	99.90	gold quality
visceral pleura	UBERON:0002401	99.90	gold quality
caput epididymis	UBERON:0004358	99.87	gold quality
colonic epithelium	UBERON:0000397	99.86	gold quality
cartilage tissue	UBERON:0002418	99.86	gold quality
cranial nerve II	UBERON:0000941	99.85	gold quality
pigmented layer of retina	UBERON:0001782	99.85	gold quality
epithelium of mammary gland	UBERON:0003244	99.85	gold quality
mammary duct	UBERON:0001765	99.84	gold quality
parotid gland	UBERON:0001831	99.84	gold quality
corpus epididymis	UBERON:0004359	99.84	gold quality
esophagus squamous epithelium	UBERON:0006920	99.84	gold quality
trabecular bone tissue	UBERON:0002483	99.83	gold quality
inferior olivary complex	UBERON:0002127	99.82	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.82	gold quality
cauda epididymis	UBERON:0004360	99.82	gold quality
nephron tubule	UBERON:0001231	99.81	gold quality
skin of hip	UBERON:0001554	99.81	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.81	gold quality
epithelium of nasopharynx	UBERON:0001951	99.80	gold quality
endometrium	UBERON:0001295	99.79	gold quality
mammary gland	UBERON:0001911	99.79	gold quality
left ovary	UBERON:0002119	99.79	gold quality

Single-cell (SCXA)

Detected in 46 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	4443.61
E-HCAD-1	yes	2943.72
E-HCAD-13	yes	2823.11
E-MTAB-10042	yes	2717.80
E-MTAB-9221	yes	2162.10
E-GEOD-125970	yes	1968.58
E-CURD-122	yes	1856.91
E-MTAB-5061	yes	855.23
E-MTAB-8142	yes	101.08
E-HCAD-11	yes	55.34
E-CURD-88	yes	47.54
E-MTAB-10553	yes	47.51
E-CURD-112	yes	42.35
E-GEOD-134144	yes	33.39
E-CURD-46	yes	28.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TRA2B	Unknown

Upstream regulators (CollecTRI, top): AR, MYC

miRNA regulators (miRDB)

38 targeting HNRNPA1, 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-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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-496	98.66	69.80	931
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-649	97.96	67.21	704

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins (PMID:11779509)
• acts as a potent regulator of G alpha(s) isoform expression (PMID:11825891)
• hnRNP A1 nucleocytoplasmic shuttling activity is required for normal myelopoiesis and BCR/ABL leukemogenesis. (PMID:11884611)
• interference with the binding of the human T cell leukemia virus type 1 rex regulatory protein to its response element (PMID:11893730)
• hnRNP A1/A2 binding sites control 5’ splice site selection in the hnRNP A1 mRNA precursor (PMID:12060656)
• High-affinity hnRNP A1 binding sites and duplex-forming inverted repeats have similar effects on 5’ splice site selection in support of a common looping out and repression mechanism. (PMID:12212851)
• A Janus splicing regulatory element modulates HIV-1 tat and rev mRNA production by coordination of hnRNP A1 cooperative binding (PMID:12419255)
• hnRNP A1 repressed c-src splicing in vitro. The activity of these exonic splicing regulators, SF2/ASF and hnRNP A1, is linked to the splicing of an exon primarily controlled by intronic factors. (PMID:12612063)
• role in c-H-ras alternative splicing regulation (PMID:12665590)
• Specific interaction of HNRPA1 with the -219T allelic form modulates Apolipoprotein E promoter activity. (PMID:12799433)
• 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)
• The expression of A1/A2 proteins is elevated in a variety of human cancers, whereas A1/A2 expression is lower or absent in normal tissues. (PMID:14633690)
• heterogeneous nuclear ribonucleoprotein A1 function has a role as constitutive KCS element components of the interferon-inducible RNA-dependent protein kinase promoter (PMID:14645369)
• hnRNP A1 binding to the exonic splicing silencer element inhibits splicing of the upstream intron by directly masking the SC35 binding site (PMID:14703516)
• hnRNP A1 and ASF/SF2 and SC35 have antagonistic roles in splicing of beta-tropomyosin exon 6B (PMID:15208309)
• used UP1’s novel DNA binding to investigate how RNA recognition motifs bind nucleic acid bases through their highly conserved RNP consensus sequences (PMID:15342234)
• HNRNPA1 is a novel internal ribosome entry site trans-acting factor that modulates alternative initiation of translation of the fibroblast growth factor 2 mRNA (PMID:15525641)
• the basal expression of gamma-fibrinogen is regulated by a constitutive transcriptional repressor protein, hnRNP A1, and the decreased binding activity of hnRNP A1 leads to the overexpression of gamma chain in HepG2 cells that overexpress the Bbeta chain (PMID:15671034)
• These observations provide an insight into a new cellular control of HTLV-1 replication and suggest that hnRNP A1 is likely part of the regulatory mechanisms of the life cycle of this human retrovirus in T cells. (PMID:15703079)
• nhRNP A1 may contribute to maintenance of telomere repeats in cancer cells with enhanced cell proliferation, or hnRNP A1 quantitative alteration could facilitate colon epithelial cell transformation through transcriptional and translational perturbation (PMID:15703818)
• This suggests an important role for the cross-reactive immune response between HTLV-1 and hnRNP A1 in the pathogenesis of immune-mediated neurological diseases via molecular mimicry. (PMID:16600502)
• We propose that hnRNP A1 stimulates telomere elongation through unwinding of a G-quadruplex or G-G hairpin structure formed at each translocation step. (PMID:16603717)
• SC35, SRp40, and heterogeneous nuclear ribonucleoprotein A1 interact competitively at the HIV-1 Tat exon 2 splicing site (PMID:16990281)
• The loss of hnRNP A1 expression might activate the ARA54-enhanced cell growth and contribute to the prostate cancer progression. (PMID:17110431)
• These results indicate that the host proteins hnRNP A1 and septin 6 play important roles in the replication of HCV through RNA-protein and protein-protein interactions. (PMID:17229681)
• cytoplasmic hnRNP A1 is a negative regulator of XIAP internal ribosome entry site (IRES)-dependent translation, indicating a novel function for the cytoplasmic form of this protein. (PMID:17287399)
• This study demonstrates that binding of hnRNPA1 to Alu elements on either side of exon 7 in the transcribed pre-mRNA is involved in alternative splicing of amyloid precursor protein exons 7 and 8. (PMID:17353911)
• hnRNP A1 binds specifically to the primary RNA sequence pri-miR-18a before Drosha processing. (PMID:17558416)
• SMN2 exon 7 splicing is repressed by an hnRNPA1-dependent exonic splicing silencer. (PMID:17884807)
• cytoplasmic redistribution of hnRNP A1 after rhinovirus infection leads to enhanced rhinovirus internal ribosome entry site-mediated translation (PMID:17898077)
• We show here that hnRNP A1 is also up-regulated during differentiation of human papillomavirus type 16 virus-infected epithelial cells in monolayer and organotypic raft culture. (PMID:17950949)
• The binding of the splicing factors hnRNPA1/A2 and DAZAP1 is the primary determinant of T6 BRCA1 exon 18 exclusion. (PMID:18391021)
• hnRNP A1 has a role in mediating rapamycin-induced alterations of cyclin D1 and c-myc IRES activity in an Akt-dependent manner and provide the first direct link between Akt and the regulation of IRES activity (PMID:18562319)
• The heterogeneous nuclear ribonucleoprotein A1 enhances the destabilization of Inhibitor of Apoptosis Proteins messenger RNA during UV irradiation. (PMID:18846111)
• These data suggest that vesiculovirus promotes hnRNPA1 relocalization in a Rae1-dependent manner for apoptotic signaling. (PMID:19004954)
• hnRNP A1/Up1 completely abrogates the cooperative quadruplex-to-ssDNA transition that characterizes the KRAS quadruplex and facilitates the association between the quadruplex and its complementary polypyrimidine strand. (PMID:19282454)
• Cytoplasmic relocalization of hnRNP A1 controls not only the IRES-dependent but also non-IRES-dependent translation initiations of RNA viruses. (PMID:19339352)
• We confirmed impairment in phosphorylation of hnRNP-A1 and binding of hnRNP-A1 to the IL10 locus in peripheral blood mononuclear cells from patients with Crohn’s disease who bear the 3020insC mutation and have lower production of IL-10. (PMID:19349988)
• expression levels and subcellular distribution of hnRNP A1 are regulated in a p38 MAPK-dependent manner (PMID:19430204)
• when two distant high-affinity sites are present on the same RNA, they facilitate cooperative spreading of hnRNP A1 between the two sites. (PMID:19667073)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hnrnpa1b	ENSDARG00000036675
mus_musculus	Hnrnpa1	ENSMUSG00000046434
rattus_norvegicus	Hnrnpa1	ENSRNOG00000036839

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), 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 ribonucleoprotein A1 — P09651 (reviewed: P09651)

Alternative names: Helix-destabilizing protein, Single-strand RNA-binding protein, hnRNP core protein A1

All UniProt accessions (57): P09651, A0A024RB53, A0A7I2V2F1, A0A7I2V2L6, A0A7I2V2M7, A0A7I2V2Q7, A0A7I2V2R4, A0A7I2V2W8, A0A7I2V2X1, A0A7I2V2Z4, A0A7I2V334, A0A7I2V360, A0A7I2V3C7, A0A7I2V3F4, A0A7I2V3J5, A0A7I2V3K5, A0A7I2V3R8, A0A7I2V3S1, A0A7I2V3U8, A0A7I2V3U9, A0A7I2V3W0, A0A7I2V3W4, A0A7I2V434, A0A7I2V453, A0A7I2V459, A0A7I2V497, A0A7I2V4E2, A0A7I2V4F8, A0A7I2V4M0, A0A7I2V4P7, A0A7I2V4R7, A0A7I2V520, A0A7I2V595, A0A7I2V5H0, A0A7I2V5L7, A0A7I2V5N7, A0A7I2V5P1, A0A7I2V5T1, A0A7I2V5U9, A0A7I2V5W8, A0A7I2V661, A0A7I2V666, A0A7I2YQ85, A0A7I2YQJ2, A0A7I2YQR6, A0A7I2YQU4, A0A7I2YQV3, A0A7I2YQV6, A0A7I2YQW0, A0A7I2YQX9, A0A7I2YQY2, F8VTQ5, F8VYN5, F8VZ49, F8W646, F8W6I7, H0YH80

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection. 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. Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1. May bind to specific miRNA hairpins. (Microbial infection) May play a role in HCV RNA replication. (Microbial infection) Cleavage by Enterovirus 71 protease 3C results in increased translation of apoptosis protease activating factor APAF1, leading to apoptosis.

Subunit / interactions. Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with SEPT6. Interacts with C9orf72. Interacts with KHDRBS1. Interacts with UBQLN2. Interacts with PPIA/CYPA. Interacts (via the RGG-box) with the HOXB-AS3 peptide; the interaction inhibits binding of HNRNPA1 to the intronic sequences flanking exon 9 of the PKM gene, preventing inclusion of exon 9 and promoting inclusion of exon 10 which suppresses formation of the PKM M2 isoform and promotes production of the M1 isoform. (Microbial infection) Interacts with HCV NS5B and with the 5’-UTR and 3’-UTR of HCV RNA. (Microbial infection) May interact with SARS-CoV Nucleoprotein.

Subcellular location. Nucleus. Cytoplasm Cytoplasm Nucleus.

Post-translational modifications. Arg-194, Arg-206 and Arg-225 are dimethylated, probably to asymmetric dimethylarginine. Sumoylated.

Disease relevance. Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (IBMPFD3) [MIM:615424] 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. Amyotrophic lateral sclerosis 20 (ALS20) [MIM:615426] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. The disease is caused by variants affecting the gene represented in this entry. Myopathy, distal, 3 (MPD3) [MIM:610099] An autosomal dominant skeletal muscle disorder characterized by adult onset of slowly progressive distal muscular weakness and atrophy affecting the upper and lower limbs, leading to difficulties using the hands and walking difficulties. Proximal muscle involvement may occur later in the disease, but patients typically remain ambulatory. Muscle biopsy shows myopathic changes with rimmed vacuoles. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. Is twenty times more abundant than isoform A1-B.

Isoforms (3)

UniProt ID	Names	Canonical?
P09651-1	A1-B	yes
P09651-2	A1-A
P09651-3	2

RefSeq proteins (2): NP_002127, NP_112420* (*=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
IPR034516	hnRNPA1/3_RRM2	Domain
IPR034845	hnRNPA1_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF11627

UniProt features (98 total): modified residue 33, strand 14, helix 8, cross-link 7, region of interest 6, sequence variant 6, mutagenesis site 6, turn 5, compositionally biased region 3, sequence conflict 3, chain 2, domain 2, splice variant 2, initiator methionine 1

Structure

Experimental structures (PDB)

73 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5ZGL	X-RAY DIFFRACTION	0.95
6J60	ELECTRON CRYSTALLOGRAPHY	0.96
1L3K	X-RAY DIFFRACTION	1.1
6BXX	X-RAY DIFFRACTION	1.1
9F4G	X-RAY DIFFRACTION	1.4
9F4H	X-RAY DIFFRACTION	1.4
9F4J	X-RAY DIFFRACTION	1.4
9F4L	X-RAY DIFFRACTION	1.4
9F4N	X-RAY DIFFRACTION	1.4
9F4O	X-RAY DIFFRACTION	1.4
9F4P	X-RAY DIFFRACTION	1.4
9F4Q	X-RAY DIFFRACTION	1.4
9F4S	X-RAY DIFFRACTION	1.4
9F4U	X-RAY DIFFRACTION	1.4
9F4V	X-RAY DIFFRACTION	1.4
9F4Y	X-RAY DIFFRACTION	1.4
9F5F	X-RAY DIFFRACTION	1.4
5ZGD	X-RAY DIFFRACTION	1.4
9F4T	X-RAY DIFFRACTION	1.42
9F7H	X-RAY DIFFRACTION	1.43
9F5C	X-RAY DIFFRACTION	1.45
9F5E	X-RAY DIFFRACTION	1.45
9F1S	X-RAY DIFFRACTION	1.5
9F4D	X-RAY DIFFRACTION	1.5
9F50	X-RAY DIFFRACTION	1.5
9F51	X-RAY DIFFRACTION	1.5
9F52	X-RAY DIFFRACTION	1.5
8RZV	X-RAY DIFFRACTION	1.51
9GPJ	X-RAY DIFFRACTION	1.53
9F55	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09651-F1	70.09	0.45

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 (40): 1, 2, 2, 3, 4, 6, 22, 192, 194, 194, 194, 199, 206, 206, 206, 218, 218, 225, 225, 225 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
218	abolishes interaction with hoxb-as3 peptide; when associated with a-225 and a-232.
225	abolishes interaction with hoxb-as3 peptide; when associated with a-218 and a-232.
232	abolishes interaction with hoxb-as3 peptide; when associated with a-218 and a-225.
326	no nuclear import nor export.
327	no nuclear import nor export.
334–335	normal nuclear import and export.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-6803529	FGFR2 alternative splicing
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9692914	SARS-CoV-1-host interactions
R-HSA-9735869	SARS-CoV-1 modulates host translation machinery
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-190236	Signaling by FGFR
R-HSA-5654738	Signaling by FGFR2
R-HSA-5663205	Infectious disease
R-HSA-72172	mRNA Splicing
R-HSA-8953854	Metabolism of RNA
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 589 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, E2F_Q4_01, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, TGCGCANK_UNKNOWN, SWEET_KRAS_ONCOGENIC_SIGNATURE, GCM_NPM1, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, REACTOME_SIGNALING_BY_FGFR, MORF_UBE2I, AAGCCAT_MIR135A_MIR135B, HSIAO_HOUSEKEEPING_GENES, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING

GO Biological Process (14): alternative mRNA splicing, via spliceosome (GO:0000380), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splicing, via spliceosome (GO:0000398), RNA export from nucleus (GO:0006405), negative regulation of telomere maintenance via telomerase (GO:0032211), positive regulation of telomere maintenance via telomerase (GO:0032212), cellular response to glucose starvation (GO:0042149), regulation of RNA splicing (GO:0043484), mRNA transport (GO:0051028), nuclear export (GO:0051168), import into nucleus (GO:0051170), cellular response to sodium arsenite (GO:1903936), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (13): DNA binding (GO:0003677), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), single-stranded RNA binding (GO:0003727), mRNA 3’-UTR binding (GO:0003730), protein domain specific binding (GO:0019904), miRNA binding (GO:0035198), pre-mRNA binding (GO:0036002), identical protein binding (GO:0042802), telomeric repeat-containing RNA binding (GO:0061752), G-rich strand telomeric DNA binding (GO:0098505), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), synapse (GO:0045202), extracellular exosome (GO:0070062), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Signaling by FGFR2	1
mRNA Splicing	1
Metabolism of RNA	1
SARS-CoV-1 Infection	1
SARS-CoV-1-host interactions	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by FGFR	1
Disease	1
Processing of Capped Intron-Containing Pre-mRNA	1
Signal Transduction	1
SARS-CoV Infections	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA binding	3
RNA transport	2
telomere maintenance via telomerase	2
regulation of telomere maintenance via telomerase	2
nucleocytoplasmic transport	2
intercellular transport	2
RNA processing	2
nucleic acid binding	2
protein binding	2
binding	2
mRNA splicing, via spliceosome	1
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
nuclear export	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
cellular response to starvation	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
cellular response to arsenic-containing substance	1
cellular response to salt	1
response to sodium arsenite	1
mRNA metabolic process	1
DNA binding	1
mRNA binding	1
regulatory RNA binding	1
single-stranded telomeric DNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
cytoplasm	1
cell junction	1

Protein interactions and networks

STRING

4590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPA1	TNPO1	Q92973	995
HNRNPA1	HNRNPC	P07910	989
HNRNPA1	TARDBP	Q13148	978
HNRNPA1	HNRNPH1	P31943	959
HNRNPA1	PTBP1	P26599	936
HNRNPA1	SRSF1	Q07955	935
HNRNPA1	HNRNPA2B1	P22626	918
HNRNPA1	SRSF5	Q13243	896
HNRNPA1	SMN1	Q16637	889
HNRNPA1	DROSHA	Q9NRR4	889
HNRNPA1	HNRNPU	Q00839	877
HNRNPA1	MATR3	P43243	862
HNRNPA1	FUS	P35637	856
HNRNPA1	HNRNPL	P14866	852
HNRNPA1	HNRNPK	P61978	850

IntAct

379 interactions, top by confidence:

A	B	Type	Score
HNRNPA1	KHDRBS1	psi-mi:“MI:0915”(physical association)	0.870
HNRNPA1	KHDRBS1	psi-mi:“MI:0403”(colocalization)	0.870
HNRNPC	KPNA3	psi-mi:“MI:0914”(association)	0.850
EGFR	HSP90AA1	psi-mi:“MI:0914”(association)	0.820
HNRNPC	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.790
HNRNPC	HNRNPA1	psi-mi:“MI:0914”(association)	0.790
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
RBM45	HNRNPA1	psi-mi:“MI:0914”(association)	0.740
RBM45	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.740
RBM45	HNRNPA1	psi-mi:“MI:0403”(colocalization)	0.740
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HNRNPA2B1	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.670
FUS	HNRNPA1	psi-mi:“MI:0914”(association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
EIF4A3	HNRNPA1	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
HNRNPA1	DDX21	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA1	HNRNPA3	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA1	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.540
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
UBQLN2	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.520
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (1647): HNRNPA1 (Reconstituted Complex), HNRNPA1 (Protein-peptide), HNRNPA1 (Affinity Capture-Western), HNRNPA1 (Affinity Capture-MS), HNRNPA1 (Protein-peptide), HNRNPA1 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), FEN1 (Two-hybrid), HNRNPA1 (Reconstituted Complex), HNRNPA1 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A0LLY1, A0A2R8Y4L2, A5A6H4, O89086, O93235, P04256, P09651, P09867, P10979, P17130, P21522, P27484, P49310, P49311, P49312, P51968, P51989, P51991, P51992, P60824, P60825, P60826, P98179, Q03250, Q03251, Q03878, Q05966, Q13151, Q14011, Q28521, Q28IQ9, Q2HJ60, Q32P51, Q38896, Q41188, Q43472, Q5RF83, Q61B10, Q6URK4, Q8BG05

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

13 interactions.

A	Effect	B	Mechanism
AKT	down-regulates	HNRNPA1	phosphorylation
AKT1	down-regulates	HNRNPA1	phosphorylation
HNRNPA1	“up-regulates quantity by expression”	TRA2B	“transcriptional regulation”
D-glucitol	“down-regulates activity”	HNRNPA1	relocalization
Osmotic_stress	“down-regulates activity”	HNRNPA1	relocalization
TARDBP	up-regulates	HNRNPA1	“post transcriptional regulation”
HNRNPA1	up-regulates	Alternative_Splicing_Regulation
MYC	“up-regulates quantity by expression”	HNRNPA1	“transcriptional regulation”
RPS6KB2	“up-regulates activity”	HNRNPA1	phosphorylation
PRKCA	down-regulates	HNRNPA1	phosphorylation
TNPO1	“up-regulates activity”	HNRNPA1	relocalization
UBQLN2	“up-regulates quantity by stabilization”	HNRNPA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 203 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
Oncogenic MAPK signaling	6	11.1×	2e-03
Recycling pathway of L1	6	10.0×	2e-03
Aggrephagy	5	9.3×	9e-03
mRNA 3’-end processing	6	8.8×	4e-03
mRNA Polyadenylation	12	7.9×	2e-05
Signaling by BRAF and RAF1 fusions	6	7.6×	7e-03
Cargo recognition for clathrin-mediated endocytosis	9	7.0×	1e-03
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	9	6.6×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
random inactivation of X chromosome	5	28.5×	3e-04
amyloid fibril formation	5	18.4×	1e-03
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	14.3×	3e-03
positive regulation of DNA repair	6	13.1×	1e-03
mitophagy	6	11.6×	2e-03
mRNA stabilization	5	11.2×	5e-03
intrinsic apoptotic signaling pathway	5	10.9×	5e-03
autophagosome maturation	5	10.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	17
Uncertain significance	49
Likely benign	35
Benign	8

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
135594	NM_031157.4(HNRNPA1):c.973T>C (p.Phe325Leu)	Pathogenic
135595	NM_031157.4(HNRNPA1):c.973T>G (p.Phe325Val)	Pathogenic
135600	NM_031157.4(HNRNPA1):c.997T>C (p.Phe333Leu)	Pathogenic
2575312	NM_031157.4(HNRNPA1):c.1064-63_*4+37del	Pathogenic
135592	NM_031157.4(HNRNPA1):c.943T>C (p.Phe315Leu)	Likely pathogenic
135593	NM_031157.4(HNRNPA1):c.949A>G (p.Asn317Asp)	Likely pathogenic
135596	NM_031157.4(HNRNPA1):c.979C>T (p.Pro327Ser)	Likely pathogenic
135597	NM_031157.4(HNRNPA1):c.982A>C (p.Met328Leu)	Likely pathogenic
135598	NM_031157.4(HNRNPA1):c.987G>T (p.Lys329Asn)	Likely pathogenic
135599	NM_031157.4(HNRNPA1):c.995A>G (p.Asn332Ser)	Likely pathogenic
135601	NM_031157.4(HNRNPA1):c.1006A>G (p.Arg336Gly)	Likely pathogenic
135602	NM_031157.4(HNRNPA1):c.1009A>G (p.Ser337Gly)	Likely pathogenic
135603	NM_031157.4(HNRNPA1):c.1040A>G (p.Tyr347Cys)	Likely pathogenic
135604	NM_031157.4(HNRNPA1):c.1042T>C (p.Phe348Leu)	Likely pathogenic
135605	NM_031157.4(HNRNPA1):c.1052C>T (p.Pro351Leu)	Likely pathogenic
135607	NM_031157.4(HNRNPA1):c.1057A>G (p.Asn353Asp)	Likely pathogenic
135608	NM_031157.4(HNRNPA1):c.1058A>G (p.Asn353Ser)	Likely pathogenic
2683801	NM_031157.4(HNRNPA1):c.1113_*2delinsTAA (p.Arg371_Ter373delinsSerXaa)	Likely pathogenic
637023	NM_031157.4(HNRNPA1):c.1018C>G (p.Pro340Ala)	Likely pathogenic
65451	NM_031157.4(HNRNPA1):c.941A>T (p.Asp314Val)	Likely pathogenic
65452	NM_031157.4(HNRNPA1):c.940G>A (p.Asp314Asn)	Likely pathogenic

SpliceAI

1043 predictions. Top by Δscore:

Variant	Effect	Δscore
12:54281383:TA:T	acceptor_loss	1.0000
12:54281384:A:AG	acceptor_gain	1.0000
12:54281384:AGTC:A	acceptor_loss	1.0000
12:54281385:G:GT	acceptor_gain	1.0000
12:54281385:GT:G	acceptor_gain	1.0000
12:54281385:GTCT:G	acceptor_gain	1.0000
12:54281385:GTCTC:G	acceptor_gain	1.0000
12:54281498:GTGTG:G	donor_gain	1.0000
12:54281499:TGTGG:T	donor_loss	1.0000
12:54281500:GTG:G	donor_gain	1.0000
12:54281502:GGTA:G	donor_loss	1.0000
12:54281503:GTAAG:G	donor_loss	1.0000
12:54281504:TAAGA:T	donor_loss	1.0000
12:54281789:TCTCA:T	acceptor_loss	1.0000
12:54281790:CTCAG:C	acceptor_loss	1.0000
12:54281937:GAGAA:G	donor_gain	1.0000
12:54281939:G:GT	donor_gain	1.0000
12:54281939:GAA:G	donor_gain	1.0000
12:54281939:GAAG:G	donor_loss	1.0000
12:54281942:G:GG	donor_gain	1.0000
12:54281942:G:T	donor_loss	1.0000
12:54281943:T:A	donor_loss	1.0000
12:54281944:GA:G	donor_gain	1.0000
12:54281946:G:GG	donor_gain	1.0000
12:54282085:A:AG	acceptor_gain	1.0000
12:54282085:ATTAG:A	acceptor_gain	1.0000
12:54282087:TA:T	acceptor_loss	1.0000
12:54282087:TAGG:T	acceptor_gain	1.0000
12:54282088:A:AG	acceptor_gain	1.0000
12:54282088:AG:A	acceptor_gain	1.0000

AlphaMissense

2451 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:54281411:G:T	R14M	1.000
12:54281412:G:C	R14S	1.000
12:54281412:G:T	R14S	1.000
12:54281413:A:C	K15Q	1.000
12:54281413:A:G	K15E	1.000
12:54281414:A:C	K15T	1.000
12:54281414:A:T	K15M	1.000
12:54281415:G:C	K15N	1.000
12:54281415:G:T	K15N	1.000
12:54281417:T:A	L16H	1.000
12:54281417:T:C	L16P	1.000
12:54281419:T:A	F17I	1.000
12:54281419:T:C	F17L	1.000
12:54281419:T:G	F17V	1.000
12:54281420:T:C	F17S	1.000
12:54281420:T:G	F17C	1.000
12:54281421:C:A	F17L	1.000
12:54281421:C:G	F17L	1.000
12:54281423:T:A	I18N	1.000
12:54281423:T:G	I18S	1.000
12:54281425:G:A	G19R	1.000
12:54281425:G:C	G19R	1.000
12:54281426:G:A	G19E	1.000
12:54281426:G:T	G19V	1.000
12:54281428:G:A	G20R	1.000
12:54281428:G:C	G20R	1.000
12:54281428:G:T	G20W	1.000
12:54281429:G:A	G20E	1.000
12:54281429:G:T	G20V	1.000
12:54281432:T:C	L21S	1.000

dbSNP variants (sampled 300 via entrez): RS1000225571 (12:54285566 G>A), RS1001029851 (12:54279835 G>A,T), RS1001362053 (12:54280072 C>A,G), RS1001833003 (12:54280231 A>G), RS1001870140 (12:54283505 T>C), RS1001896286 (12:54283018 C>G,T), RS1002566968 (12:54287376 G>A), RS1002789576 (12:54280726 A>C,G), RS1003215452 (12:54280780 C>A,G,T), RS1003572208 (12:54286075 G>A), RS1003603418 (12:54286556 C>A,G,T), RS1003827001 (12:54279831 C>T), RS1004199206 (12:54279681 C>A), RS1004303054 (12:54285666 A>G), RS1004653677 (12:54285991 C>A)

Disease associations

OMIM: gene MIM:164017 | disease phenotypes: MIM:615424, MIM:615426, MIM:610099, MIM:160500, MIM:167320

GenCC curated gene-disease

Disease	Classification	Inheritance
inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3	Strong	Autosomal dominant
amyotrophic lateral sclerosis type 20	Strong	Autosomal dominant
inclusion body myopathy with Paget disease of bone and frontotemporal dementia	Supportive	Autosomal dominant
amyotrophic lateral sclerosis	Supportive	Autosomal dominant

Mondo (8): inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (MONDO:0014179), amyotrophic lateral sclerosis type 20 (MONDO:0014181), relapsing-remitting multiple sclerosis (MONDO:0005314), chronic progressive multiple sclerosis (MONDO:0005284), Finnish upper limb-onset distal myopathy (MONDO:0012410), distal myopathy (MONDO:0018949), inclusion body myopathy with Paget disease of bone and frontotemporal dementia (MONDO:0000507), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (4): Amyotrophic lateral sclerosis (Orphanet:803), HNRNPA1-related adult-onset distal myopathy (Orphanet:399086), Distal myopathy (Orphanet:599), Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (Orphanet:52430)

HPO phenotypes

113 total (30 of 113 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000217	Xerostomia
HP:0000518	Cataract
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000925	Abnormality of the vertebral column
HP:0001171	Split hand
HP:0001249	Intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001288	Gait disturbance
HP:0001293	Cranial nerve compression
HP:0001308	Tongue fasciculations
HP:0001347	Hyperreflexia
HP:0001397	Hepatic steatosis
HP:0001618	Dysphonia
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001760	Abnormal foot morphology
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002145	Frontotemporal dementia
HP:0002180	Neurodegeneration
HP:0002300	Mutism
HP:0002307	Drooling
HP:0002312	Clumsiness
HP:0002313	Spastic paraparesis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005962_20	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-13
GCST010143_26	Meat-related diet	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008111	diet 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
D020528	Multiple Sclerosis, Chronic Progressive	C10.114.375.500.200; C10.314.350.500.200; C20.111.258.250.500.200; C23.550.291.500.625
D020529	Multiple Sclerosis, Relapsing-Remitting	C10.114.375.500.600; C10.314.350.500.600; C20.111.258.250.500.600

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1955709 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one	IC50	72800 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.08	Kd	82.7	nM	CAMPTOTHECIN

PubChem BioAssay actives

3 with measured affinity, of 10 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
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	648268: Binding affinity to recombinant GST-tagged human hnRNP A1 expressed in Escherichia coli using QCM biosensor by Scatchard plot analysis	kd	0.0827	uM
Quercetin	1802891: Surface Plasmon Resonance (SPR) Assay from Article 10.1074/jbc.M114.553248: “Chemical proteomics identifies heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as the molecular target of quercetin in its anti-cancer effects in PC-3 cells.”	kd	1.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases expression, affects binding, increases reaction	3
Tobacco Smoke Pollution	affects expression, decreases methylation, increases methylation	3
bisphenol A	decreases expression, increases methylation	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases reaction, increases expression, decreases expression, decreases reaction, affects localization	2
Arsenic Trioxide	increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases expression, affects reaction	2
Caffeine	decreases expression, decreases phosphorylation	2
Doxorubicin	affects expression, increases expression	2
Fluorouracil	decreases expression, affects reaction	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
beryllium sulfate	increases expression	1
nickel sulfate	increases expression	1
coumarin	affects phosphorylation	1
cadmium sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1960737	Binding	Binding affinity to human hnRNP A1 expressed in HeLa cells after 16 hrs by avidin-agarose bead pull down assay	Camptothecin (CPT) directly binds to human heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and inhibits the hnRNP A1/topoisomerase I interaction. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2YX	Abcam HEK293T HNRNPA1 KO	Transformed cell line	Female
CVCL_E4W1	KOLF2.1J HNRNPA1 5.1kbdel DEL/WT	Induced pluripotent stem cell	Male
CVCL_E7L1	KOLF2.1J HNRNPA1 D262N SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7L2	KOLF2.1J HNRNPA1 D262N SNV/WT	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

579 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)
NCT00078338	PHASE4	COMPLETED	Rebif® Versus Copaxone® in the Treatment of Relapsing Remitting Multiple Sclerosis
NCT00101959	PHASE4	WITHDRAWN	Implementation Study of Treatment Optimization Recommendations on Relapsing-Remitting Multiple Sclerosis (RR MS) Subjects
NCT00168766	PHASE4	COMPLETED	Avonex (Interferon-beta-1a) and Avonex Plus Methylprednisolone for the Treatment of Relapsing-remitting MS
NCT00202995	PHASE4	TERMINATED	Randomized Study Designed to Look at Disease Progression Using 2 Currently FDA Approved Drugs for the Treatment of RRMS
NCT00203021	PHASE4	COMPLETED	Glatiramer Acetate (Copaxone®) Study to Follow Participants From the First Original Study for Safety and Effectiveness
NCT00203047	PHASE4	TERMINATED	Assessment Study of Steroid Effect in Relapsing Multiple Sclerosis Subjects Treated With Glatiramer Acetate
NCT00315367	PHASE4	COMPLETED	A fMRI(Functional Magnetic Resonance Imaging) Research Study to Learn More About Multiple Sclerosis and Individuals Potentially Experiencing Memory Difficulties
NCT00317941	PHASE4	COMPLETED	Safety Study in Relapsing-remitting Multiple Sclerosis (RRMS) Patients Receiving Betaferon or Rebif
NCT00367484	PHASE4	COMPLETED	Study To Evaluate The Immunogenicity And Safety Of r-hIFN Beta-1a (Rebif®) Using Clone 484-39 In Multiple Sclerosis
NCT00492466	PHASE4	COMPLETED	Investigating if Interferon-Beta Can be Used in Patients With MS After They Have Developed Neutralizing Antibodies
NCT00493116	PHASE4	COMPLETED	Is IFN-beta Treatment in MS Useful After a Washout Period in Patients With Neutralizing Antibodies to Interferon Beta
NCT00534261	PHASE4	COMPLETED	Does Quality of Life Improve in Multiple Sclerosis Patients Treated With Interferon Beta-1a?
NCT00574041	PHASE4	TERMINATED	How Side Effects of Avonex Are Affected by Gradually Increasing to Full Dose vs Starting at Full Dose
NCT00771043	PHASE4	WITHDRAWN	A Proof-of-Concept Study to Correlate Retinal Nerve Fiber Layer Changes in Patients With Multiple Sclerosis Treated With Natalizumab or Interferon Beta 1-a
NCT00871780	PHASE4	COMPLETED	A Prospective, Open-label, Non-randomized, Clinical Trial to Determine if Natalizumab (Tysabri®) Improves Ambulatory Measures in Relapsing-remitting Multiple Sclerosis (RRMS) Patients
NCT01144052	PHASE4	COMPLETED	Natalizumab De-escalation With Interferon Beta-1b
NCT01225289	PHASE4	COMPLETED	Impact of Vitamin A Supplementation on Immune System in Multiple Sclerosis Patients
NCT01310166	PHASE4	COMPLETED	Biomarker Study After Initiation of Treatment With Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis
NCT01317004	PHASE4	COMPLETED	Patients With Relapse Remitting Multiple Sclerosis (RRMS): Candidates for MS Therapy Change
NCT01407211	PHASE4	UNKNOWN	Impact of Vitamin A on Gene Expression, in Multiple Sclerosis Patient
NCT01417273	PHASE4	UNKNOWN	Impact of Vitamin A on Multiple Sclerosis (MS)
NCT01436643	PHASE4	TERMINATED	Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression
NCT01498887	PHASE4	COMPLETED	Efficacy of Fingolimod in de Novo Patients Versus Fingolimod in Patients Previously Treated With a First Line Disease Modifying Therapy
NCT01534182	PHASE4	COMPLETED	Evaluation of Patient Reported Outcomes in RRMS Patients Candidates for MS Therapy Change and Transitioned to Fingolimod 0.5 mg (EPOC)
NCT01623596	PHASE4	COMPLETED	Evaluation of Patient Retention of Fingolimod vs. Currently Approved Disease Modifying Therapy in Patients With Relapsing Remitting Multiple Sclerosis.
NCT01701856	PHASE4	TERMINATED	Natalizumab De-escalation to Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis
NCT01705457	PHASE4	UNKNOWN	Impact of Vitamin A on RAR Gene Expression in Multiple Sclerosis
NCT01709812	PHASE4	WITHDRAWN	Effect of an Individualized Patient Support Program on Treatment Satisfaction in Fingolimod-treated Patients With RRMS
NCT01755871	PHASE4	TERMINATED	Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis
NCT01842191	PHASE4	COMPLETED	Efficacy of Fish Oil in Multiple Sclerosis
NCT01930708	PHASE4	COMPLETED	A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes
NCT02090348	PHASE4	WITHDRAWN	Study to Evaluate Fatigue in Participants With Relapsing Remitting Multiple Sclerosis When Treated With Dimethyl Fumarate
NCT02090413	PHASE4	COMPLETED	Phase 4 Study of Effect of Aspirin on Flushing in Dimethyl Fumarate-Treated Participants With Relapsing-Remitting Multiple Sclerosis
NCT02125604	PHASE4	COMPLETED	Gastrointestinal Tolerability Study Of Dimethyl Fumarate In Participants With Relapsing-Remitting Multiple Sclerosis In Germany