HNRNPM

Summary

HNRNPM (heterogeneous nuclear ribonucleoprotein M, HGNC:5046) is a protein-coding gene on chromosome 19p13.2, encoding Heterogeneous nuclear ribonucleoprotein M (P52272). Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. It is a common-essential gene (DepMap: required in 90.2% of cancer cell lines).

This gene belongs to the 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 three repeats of quasi-RRM domains that bind to RNAs. This protein also constitutes a monomer of the N-acetylglucosamine-specific receptor which is postulated to trigger selective recycling of immature GlcNAc-bearing thyroglobulin molecules. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4670 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 128 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 90.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_005968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5046
Approved symbol	HNRNPM
Name	heterogeneous nuclear ribonucleoprotein M
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	HTGR1, HNRNPM4, HNRPM4, CEAR
Ensembl gene	ENSG00000099783
Ensembl biotype	protein_coding
OMIM	160994
Entrez	4670

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000325495, ENST00000348943, ENST00000593293, ENST00000594907, ENST00000596295, ENST00000596984, ENST00000597081, ENST00000597270, ENST00000597813, ENST00000598367, ENST00000598603, ENST00000598999, ENST00000600092, ENST00000600806, ENST00000601645, ENST00000602219, ENST00000903831, ENST00000903832, ENST00000938808, ENST00000938809, ENST00000938810, ENST00000938811, ENST00000940928

RefSeq mRNA: 3 — MANE Select: NM_005968 NM_001297418, NM_005968, NM_031203

CCDS: CCDS12203, CCDS12204

Canonical transcript exons

ENST00000325495 — 16 exons

Exon	Start	End
ENSE00000909986	8473664	8473708
ENSE00001679072	8462529	8462581
ENSE00003153491	8444975	8445111
ENSE00003209123	8488691	8489114
ENSE00003516781	8468774	8468834
ENSE00003527918	8487024	8487075
ENSE00003528679	8463497	8463504
ENSE00003533419	8483158	8483211
ENSE00003592909	8455405	8455574
ENSE00003593869	8463593	8463686
ENSE00003622325	8485603	8486405
ENSE00003646509	8467535	8467584
ENSE00003649593	8471326	8471427
ENSE00003652040	8466235	8466388
ENSE00003681894	8465324	8465515
ENSE00003785170	8474167	8474244

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 146.8316 / max 2101.5948, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173671	145.2281	1826
173676	0.8059	520
173675	0.7976	437

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.61	gold quality
germinal epithelium of ovary	UBERON:0001304	99.49	gold quality
visceral pleura	UBERON:0002401	99.41	gold quality
parietal pleura	UBERON:0002400	99.35	gold quality
esophagus squamous epithelium	UBERON:0006920	99.32	gold quality
embryo	UBERON:0000922	99.19	gold quality
pleura	UBERON:0000977	99.18	gold quality
ventricular zone	UBERON:0003053	99.14	gold quality
ganglionic eminence	UBERON:0004023	99.13	gold quality
tendon of biceps brachii	UBERON:0008188	99.10	gold quality
colonic epithelium	UBERON:0000397	99.06	gold quality
epithelium of nasopharynx	UBERON:0001951	99.00	gold quality
gingival epithelium	UBERON:0001949	98.92	gold quality
tonsil	UBERON:0002372	98.78	gold quality
left ovary	UBERON:0002119	98.77	gold quality
amniotic fluid	UBERON:0000173	98.74	gold quality
sural nerve	UBERON:0015488	98.70	gold quality
right ovary	UBERON:0002118	98.68	gold quality
cerebellar hemisphere	UBERON:0002245	98.65	gold quality
ovary	UBERON:0000992	98.63	gold quality
body of uterus	UBERON:0009853	98.63	gold quality
ectocervix	UBERON:0012249	98.60	gold quality
endocervix	UBERON:0000458	98.59	gold quality
cerebellar cortex	UBERON:0002129	98.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.59	gold quality
right lobe of thyroid gland	UBERON:0001119	98.57	gold quality
gingiva	UBERON:0001828	98.56	gold quality
cortical plate	UBERON:0005343	98.56	gold quality
monocyte	CL:0000576	98.54	gold quality
left lobe of thyroid gland	UBERON:0001120	98.50	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	17.04
E-GEOD-93593	yes	7.62
E-MTAB-6819	no	614.06
E-MTAB-11011	no	449.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting HNRNPM, 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-3064-3P	100.00	70.09	1254
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-5586-5P	96.29	68.02	685

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 25)

• mitochondrial ribosomal protein S12 3’-UTR interacts specifically with TRAP1 (tumor necrosis factor receptor-associated protein1), hnRNPM4 (heterogeneous nuclear ribonucleoprotein M4), Hsp70 and Hsp60 (heat shock proteins 70 and 60), and alpha-tubulin (PMID:18790094)
• PSF (polypyrimidine tract-binding protein-associated splicing factor) and p54(nrb), two highly related proteins involved in transcription and RNA processing, are identified as new binding partners of hnRNP M. (PMID:19874820)
• A central region in hnRNP-M is required for interaction with CDC5L/PLRG1. (PMID:20467437)
• Mechanistic control of carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) splice isoforms by the heterogeneous nuclear ribonuclear proteins hnRNP L, hnRNP A1, and hnRNP M. (PMID:21398516)
• The present data demonstrate that the upregulation of HnRNP M is involved in human colorectal epithelial carcinogenesis and may serve as a carcinoma biomarker for colorectal cancer. (PMID:24381081)
• our data suggest that TAF15 and TLS/FUS operate within similar but not identical hnRNP M-TET protein complexes to influence the transcriptional or post-transcriptional output of a particular cell type. (PMID:24474660)
• Our results provide a clue that hnRNP M is a potential therapeutic target for Spinal muscular atrophy (PMID:24533984)
• findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program. (PMID:24840202)
• Results suggest that glyceraldehyde-modified hnRNPM alters gene expression in nonalcoholic fatty liver disease. (PMID:25684943)
• The authors propose that cleavage of and subverting the function of hnRNPM by 3C protease is a general strategy utilized by picornaviruses to facilitate viral infection. (PMID:25926642)
• p54nrb and hnRNPM knockdown silences the FGF1 promoter-dependent accumulation of mRNA during myoblast differentiation. (PMID:26332123)
• Overexpression of hnRNPM promotes breast cancer aggressiveness by regulating the level of CD44s and indicates a poor prognosis. (PMID:28393427)
• Data suggest that both heterogeneous nuclear ribonucleoprotein type M (HNRPM) and solute carrier 1A5 (SLC1A5) have role in the pathogenesis of ovarian cancer. (PMID:28609484)
• the gain-of-function effect of a single mutation on MORC2 promotes metastasis of triple-negative breast cancer by regulating CD44 splicing mediated by hnRNPM (PMID:30093560)
• The role of hnRNPM in promoting IRES-containingmRNA translationfills a critical missing piece of the hypoxia-inducedgene activation. This hnRNPM-IRES-dependent function complementsthe mRNA translation pathway mediated through eIF4E2-HIF2alphatoimplement dynamic gene regulation and offers an alternative pathfor translation recovery from stress-mediated global translationalsuppression (PMID:30852162)
• Our study demonstrates that hnRNPM negatively regulated prostate cancer cell migration and invasion, and its expression can be transcriptionally inhibited by YY1 (PMID:31251827)
• The expression of splicing factor gene HNRNPM was associated with Cognitive Decline as measured by the Mini-Mental State Examinations. Age-associated dysregulation of the splicing factor expression in ageing humans may be predictive for change in in this population. (PMID:31292793)
• microR-505/heterogeneous nuclear ribonucleoprotein M inhibits hepatocellular carcinoma cell proliferation and induces cell apoptosis through the Wnt/beta-catenin signaling pathway. (PMID:32940078)
• HNRNPM controls circRNA biogenesis and splicing fidelity to sustain cancer cell fitness. (PMID:34075878)
• RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners. (PMID:34244793)
• CircURI1 interacts with hnRNPM to inhibit metastasis by modulating alternative splicing in gastric cancer. (PMID:34385309)
• Targeting HNRNPM Inhibits Cancer Stemness and Enhances Antitumor Immunity in Wnt-activated Hepatocellular Carcinoma. (PMID:35158098)
• Knockdown of HNRNPM inhibits the progression of glioma through inducing ferroptosis. (PMID:38016815)
• hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing. (PMID:38815579)
• PARP4 interacts with hnRNPM to regulate splicing during lung cancer progression. (PMID:39034402)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hnrnpm	ENSDARG00000061735
mus_musculus	Hnrnpm	ENSMUSG00000059208
rattus_norvegicus	Hnrnpm	ENSRNOG00000007921
drosophila_melanogaster	rump	FBGN0267790
caenorhabditis_elegans	sup-46	WBGENE00045383

Paralogs (1): MYEF2 (ENSG00000104177)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoprotein M — P52272 (reviewed: P52272)

All UniProt accessions (10): P52272, M0QY96, M0QYL3, M0QYQ7, M0QZM1, M0R019, M0R0N3, M0R0Y6, M0R2I7, M0R2T0

UniProt curated annotations — full annotation on UniProt →

Function. Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines.

Subunit / interactions. Identified in the spliceosome C complex. Interacts with PPIA/CYPA.

Subcellular location. Nucleus. Nucleolus.

Post-translational modifications. Sumoylated.

Isoforms (3)

UniProt ID	Names	Canonical?
P52272-1	1, M4	yes
P52272-2	2, M1-M2
P52272-3	3, M3

RefSeq proteins (3): NP_001284347, NP_005959, NP_112480 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR024666	HnRNP_M_PY-NLS	Domain
IPR034990	hnRNPM_RRM3	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050374	RRT5_SRSF_SR	Family

Pfam: PF00076, PF11532

UniProt features (101 total): repeat 27, modified residue 24, cross-link 22, strand 8, sequence conflict 5, helix 4, domain 3, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2OT8	X-RAY DIFFRACTION	3.1
2DGV	SOLUTION NMR
2DH9	SOLUTION NMR
2DO0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52272-F1	56.10	0.06

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): 2, 29, 86, 134, 204, 277, 365, 377, 397, 432, 452, 468, 481, 496, 528, 575, 588, 618, 633, 637 …

Function

Pathways and Gene Ontology

Reactome pathways

5 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-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 225 (showing top): MORF_DNMT1, MORF_SMC1L1, TTTGTAG_MIR520D, GCM_NPM1, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, REACTOME_SIGNALING_BY_FGFR, MORF_UBE2I, MORF_RRM1, MORF_HDAC1, MORF_UBE2N, MORF_RAD21, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (4): alternative mRNA splicing, via spliceosome (GO:0000380), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), protein domain specific binding (GO:0019904), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nucleolus (GO:0005730), membrane (GO:0016020), nuclear matrix (GO:0016363), paraspeckles (GO:0042382), synapse (GO:0045202), extracellular exosome (GO:0070062), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by FGFR2	1
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	3
cellular anatomical structure	3
RNA processing	2
binding	2
mRNA splicing, via spliceosome	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
protein binding	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
cell junction	1
extracellular vesicle	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
protein-containing complex	1

Protein interactions and networks

STRING

3186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPM	HNRNPH1	P31943	919
HNRNPM	HNRNPH2	P55795	919
HNRNPM	HNRNPC	P07910	912
HNRNPM	HNRNPDL	O14979	905
HNRNPM	HNRNPU	Q00839	893
HNRNPM	ILF2	Q12905	887
HNRNPM	PTBP1	P26599	876
HNRNPM	HNRNPA2B1	P22626	871
HNRNPM	MATR3	P43243	871
HNRNPM	ILF3	Q12906	869
HNRNPM	DHX9	Q08211	863
HNRNPM	DDX17	Q92841	860
HNRNPM	HNRNPL	P14866	848
HNRNPM	SFPQ	P23246	823
HNRNPM	HNRNPK	P61978	802

IntAct

367 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
ERLIN2	ERLIN1	psi-mi:“MI:0914”(association)	0.740
HNRNPM	HNRNPF	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HNRNPM	LMO2	psi-mi:“MI:0915”(physical association)	0.670
HNRNPH1	HNRNPM	psi-mi:“MI:0915”(physical association)	0.670
TNPO1	HNRNPM	psi-mi:“MI:0407”(direct interaction)	0.620
HNRNPM		psi-mi:“MI:0915”(physical association)	0.560
HNRNPM	GMCL2	psi-mi:“MI:0915”(physical association)	0.560
TEKT4	HNRNPM	psi-mi:“MI:0915”(physical association)	0.560
AKAP9	HNRNPM	psi-mi:“MI:0915”(physical association)	0.560
	HNRNPM	psi-mi:“MI:0915”(physical association)	0.560
HNRNPM	TEKT4	psi-mi:“MI:0915”(physical association)	0.560
HNRNPM	AKAP9	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA2B1	HNRNPM	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (939): HNRNPM (Affinity Capture-MS), HNRNPM (Two-hybrid), HNRNPM (Two-hybrid), AKAP9 (Two-hybrid), GMCL1P1 (Two-hybrid), TEKT4 (Two-hybrid), HNRNPM (Affinity Capture-RNA), HNRNPM (Affinity Capture-RNA), HNRNPM (Affinity Capture-RNA), HNRNPM (Affinity Capture-RNA), HNRNPM (Biochemical Activity), HNRNPM (Affinity Capture-MS), HNRNPM (Affinity Capture-MS), HNRNPM (Affinity Capture-MS), HNRNPM (Biochemical Activity)

ESM2 similar proteins: A0A2R8Y4L2, A5A6H4, A7VJC2, O01671, O17310, O19049, O61374, O88569, O97018, P04256, P09651, P09867, P17130, P19339, P21522, P22626, P31942, P49312, P51968, P51989, P51990, P51991, P51992, P52272, P61978, P61979, P61980, Q08473, Q13148, Q24668, Q28521, Q28F51, Q2HJ60, Q32P51, Q3T0D0, Q4R4M6, Q5R5H8, Q5R5W2, Q5RBU8, Q5ZIQ3

Diamond homologs: A6NDY0, O14327, O43040, O59670, P25555, P33240, P38922, P40561, P51990, P52272, Q10355, Q13151, Q14103, Q24207, Q28165, Q28IQ9, Q44554, Q44556, Q44560, Q54ZS8, Q57014, Q5RDA3, Q60668, Q640A2, Q6FVV7, Q6NVP7, Q6TY21, Q7ZXB8, Q86U42, Q8BIQ5, Q8C7E9, Q8CCS6, Q8HXM1, Q9D0E1, Q9DDY9, Q9FFZ6, Q9FJN9, Q9FXA2, Q9H0L4, Q9JJ54

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDC5L	“up-regulates activity”	HNRNPM	binding
PLRG1	“up-regulates activity”	HNRNPM	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 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
TBC/RABGAPs	6	13.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA stabilization	6	14.1×	2e-03
autophagosome maturation	5	11.2×	1e-02
mRNA splicing, via spliceosome	9	5.3×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2585 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8445108:AGGG:A	donor_gain	1.0000
19:8445109:GGG:G	donor_gain	1.0000
19:8445109:GGGG:G	donor_gain	1.0000
19:8445110:GG:G	donor_gain	1.0000
19:8445110:GGG:G	donor_gain	1.0000
19:8445111:GG:G	donor_gain	1.0000
19:8445111:GGT:G	donor_loss	1.0000
19:8445112:G:GG	donor_gain	1.0000
19:8445113:TGAG:T	donor_loss	1.0000
19:8445114:GAGTA:G	donor_loss	1.0000
19:8455396:C:A	acceptor_gain	1.0000
19:8455403:A:AG	acceptor_gain	1.0000
19:8455404:G:GA	acceptor_gain	1.0000
19:8455404:GTGAA:G	acceptor_gain	1.0000
19:8462482:T:A	acceptor_gain	1.0000
19:8462496:T:A	acceptor_gain	1.0000
19:8462502:A:AG	acceptor_gain	1.0000
19:8462503:T:G	acceptor_gain	1.0000
19:8463463:T:A	acceptor_gain	1.0000
19:8463582:T:TA	acceptor_gain	1.0000
19:8463589:ATAGT:A	acceptor_gain	1.0000
19:8463590:T:G	acceptor_gain	1.0000
19:8463590:TAG:T	acceptor_loss	1.0000
19:8463591:A:AG	acceptor_gain	1.0000
19:8463591:AGT:A	acceptor_gain	1.0000
19:8463591:AGTGT:A	acceptor_loss	1.0000
19:8463592:G:GG	acceptor_gain	1.0000
19:8463592:GT:G	acceptor_gain	1.0000
19:8463592:GTG:G	acceptor_gain	1.0000
19:8463592:GTGT:G	acceptor_gain	1.0000

AlphaMissense

4865 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8455507:A:C	R72S	1.000
19:8455507:A:T	R72S	1.000
19:8455509:C:A	A73D	1.000
19:8455512:T:C	F74S	1.000
19:8455515:T:A	I75N	1.000
19:8455515:T:C	I75T	1.000
19:8455515:T:G	I75S	1.000
19:8455520:A:G	N77D	1.000
19:8455521:A:T	N77I	1.000
19:8455522:C:A	N77K	1.000
19:8455522:C:G	N77K	1.000
19:8455524:T:A	I78K	1.000
19:8455524:T:G	I78R	1.000
19:8455527:C:G	P79R	1.000
19:8455529:T:C	F80L	1.000
19:8455530:T:G	F80C	1.000
19:8455531:T:A	F80L	1.000
19:8455531:T:G	F80L	1.000
19:8455541:T:A	W84R	1.000
19:8455541:T:C	W84R	1.000
19:8455542:G:C	W84S	1.000
19:8455542:G:T	W84L	1.000
19:8455543:G:C	W84C	1.000
19:8455543:G:T	W84C	1.000
19:8455546:G:C	Q85H	1.000
19:8455546:G:T	Q85H	1.000
19:8455551:T:A	L87H	1.000
19:8455551:T:C	L87P	1.000
19:8455551:T:G	L87R	1.000
19:8455553:A:C	K88Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000002876 (19:8457897 G>C), RS1000055547 (19:8461354 A>G), RS1000096369 (19:8468900 C>T), RS1000133679 (19:8448852 A>G), RS1000139615 (19:8467254 G>A), RS1000234098 (19:8445192 G>A,C), RS1000276429 (19:8454947 A>G), RS1000282817 (19:8480908 G>C), RS1000286777 (19:8466749 C>G,T), RS1000448136 (19:8449468 CT>C), RS1000465979 (19:8456545 G>A,T), RS1000639890 (19:8466579 G>A), RS1000659570 (19:8462980 A>G), RS1000732665 (19:8450558 T>C,G), RS1000748433 (19:8456901 C>G,T)

Disease associations

OMIM: gene MIM:160994 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005194_131	Coronary artery disease	5.000000e-07
GCST90000025_675	Appendicular lean mass	1.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291610 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.07	Kd	8568	nM	CHEMBL3752910
5.07	ED50	8568	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 14 total; 1 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148536: Binding affinity to human HNRNPM incubated for 45 mins by Kinobead based pull down assay	kd	8.5683	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects splicing, decreases expression, decreases methylation, increases expression	5
Rotenone	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
beauvericin	affects cotreatment, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
beta-lapachone	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
azoxystrobin	decreases expression	1
chloropicrin	increases expression	1
enniatins	affects cotreatment, increases expression	1
deguelin	decreases expression	1
pterostilbene	increases expression	1
K 7174	decreases expression	1
fenpyroximate	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
pyrimidifen	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	affects expression	1
bisphenol B	increases expression	1
thifluzamide	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5260017	Binding	Competitive inhibition of hnRNP M to in human A549 cells at 50 uM by immunoblotting analysis	New insight into the bioactivity of substituted benzimidazole derivatives: Repurposing from anti-HIV activity to cell migration inhibition targeting hnRNP M. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea