HNRNPF

Summary

HNRNPF (heterogeneous nuclear ribonucleoprotein F, HGNC:5039) is a protein-coding gene on chromosome 10q11.21, encoding Heterogeneous nuclear ribonucleoprotein F (P52597). Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm.

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and regulate alternative splicing, polyadenylation, 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 which have guanosine-rich sequences. This protein is very similar to the family member hnRPH. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 3185 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• Druggable target: yes
• MANE Select transcript: NM_001098204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5039
Approved symbol	HNRNPF
Name	heterogeneous nuclear ribonucleoprotein F
Location	10q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169813
Ensembl biotype	protein_coding
OMIM	601037
Entrez	3185

Gene structure

Transcript identifiers

Ensembl transcripts: 70 — 69 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000337970, ENST00000356053, ENST00000357065, ENST00000443950, ENST00000477108, ENST00000498176, ENST00000544000, ENST00000682386, ENST00000854170, ENST00000854171, ENST00000854172, ENST00000854173, ENST00000854174, ENST00000854175, ENST00000854176, ENST00000854177, ENST00000854178, ENST00000854179, ENST00000854180, ENST00000854181, ENST00000854182, ENST00000854183, ENST00000854184, ENST00000854185, ENST00000854186, ENST00000854187, ENST00000854188, ENST00000854189, ENST00000854190, ENST00000854191, ENST00000854192, ENST00000854193, ENST00000854194, ENST00000854195, ENST00000854196, ENST00000854197, ENST00000923122, ENST00000923123, ENST00000923124, ENST00000923125, ENST00000923126, ENST00000923127, ENST00000923128, ENST00000923129, ENST00000923130, ENST00000923131, ENST00000923132, ENST00000923133, ENST00000923134, ENST00000923135, ENST00000923136, ENST00000923137, ENST00000923138, ENST00000923139, ENST00000923140, ENST00000923141, ENST00000923142, ENST00000923143, ENST00000958943, ENST00000958944, ENST00000958945, ENST00000958946, ENST00000958947, ENST00000958948, ENST00000958949, ENST00000958950, ENST00000958951, ENST00000958952, ENST00000958953, ENST00000958954

RefSeq mRNA: 6 — MANE Select: NM_001098204 NM_001098204, NM_001098205, NM_001098206, NM_001098207, NM_001098208, NM_004966

CCDS: CCDS7204

Canonical transcript exons

ENST00000682386 — 4 exons

Exon	Start	End
ENSE00001360956	43394630	43394688
ENSE00001360970	43396456	43396590
ENSE00003919183	43385618	43387936
ENSE00003920985	43409131	43409186

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 139.1638 / max 499.2166, expressed in 1828 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109178	57.5382	1824
109176	44.1392	1821
109175	13.9341	1770
109172	13.4543	1735
109177	4.8530	1254
109174	2.3469	979
109170	1.0622	634
109168	0.4961	233
109169	0.4726	255
109167	0.3981	230

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.39	gold quality
ganglionic eminence	UBERON:0004023	98.23	gold quality
rectum	UBERON:0001052	98.08	gold quality
gall bladder	UBERON:0002110	98.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.86	gold quality
monocyte	CL:0000576	97.85	gold quality
leukocyte	CL:0000738	97.71	gold quality
islet of Langerhans	UBERON:0000006	97.71	gold quality
right uterine tube	UBERON:0001302	97.70	gold quality
granulocyte	CL:0000094	97.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.65	gold quality
mononuclear cell	CL:0000842	97.65	gold quality
mucosa of transverse colon	UBERON:0004991	97.43	gold quality
left uterine tube	UBERON:0001303	97.42	gold quality
transverse colon	UBERON:0001157	97.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.32	gold quality
body of stomach	UBERON:0001161	97.31	gold quality
skin of abdomen	UBERON:0001416	97.20	gold quality
upper lobe of left lung	UBERON:0008952	97.12	gold quality
omental fat pad	UBERON:0010414	97.11	gold quality
stromal cell of endometrium	CL:0002255	97.10	gold quality
skin of leg	UBERON:0001511	97.10	gold quality
peritoneum	UBERON:0002358	97.10	gold quality
right lung	UBERON:0002167	97.00	gold quality
right ovary	UBERON:0002118	96.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.96	gold quality
lower esophagus	UBERON:0013473	96.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.93	gold quality
esophagus	UBERON:0001043	96.91	gold quality
esophagus mucosa	UBERON:0002469	96.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-122	yes	23.91
E-MTAB-10553	yes	7.09
E-MTAB-10137	no	635.24
E-GEOD-81383	no	621.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting HNRNPF, 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-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Literature-anchored findings (GeneRIF, showing 23)

• Shows that hnRNPF regulates the 3’ end cleavage reaction. (PMID:11158309)
• high levels of hnRNP F are present in premalignant and malignant stages of colorectal cancer, reflecting a role for this protein early in colorectal tumorigenesis (PMID:16424007)
• The solution structure of the three quasi RNA recognition motifs of hnRNP F and identification of the residues that are important for the interaction with the Bcl-x RNA. (PMID:16885237)
• hnRNPH and F regulate DM20 splicing by recruiting U1snRNP and hnRNPH plays a primary role in DM20 splice site selection in vivo (PMID:19244236)
• heterogeneous ribonucleoprotein F is involved in the regulation of cell proliferation via the mammalian target of rapamycin/S6 kinase 2 pathway (PMID:20308064)
• Results suggest that hnRNP H and F are nuclear shuttling proteins whose posttranslational modifications may alter interaction with transportin 1, nuclear localization, and hence function. (PMID:20308327)
• The study shows solution structures of the three quasi-RNA-recognition motifs of heterogeneous nuclear ribonucleoprotein F in complex with G-tract RNA. (PMID:20526337)
• this result suggests that hnRNP F directs formation of the exon 4 minus variant of ENOX2. (PMID:21625959)
• These data point to a functional interaction between hnRNP F and SRSF1 as a mutant that eliminates SRSF1 binding to exon 11, or a SRSF1 knockdown, which prevents the stimulatory effect of hnRNP F over expression. (PMID:22132154)
• hnRNP F is a co-factor in a subset of tristetraprolin/BRF1/BRF2-mediated mRNA decay. (PMID:24978456)
• Results from a study on gene expression variability markers in early-stage human embryos shows that HNRNPF is a putative marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F, SIRTUIN-1, and FOXO3alpha than nondiabetic kidneys. (PMID:28424160)
• Simulation results demonstrate that the RNA binding domain qRRM2 of hnRNP F binds strongly with G-tract RNA, but any mutation of the G-tract leads to a drastic reduction of the binding free energy. (PMID:29050934)
• heterogeneous nuclear ribonucleoprotein F (hnRNPF) regulates G-quadruplex-associated alternative splicing across the transcriptome. (PMID:29269483)
• FOXP3 represses the ability of hnRNPF to bind to its target pre-mRNA and thus modulates RNA alternative splicing (PMID:29773655)
• hnRNP H/F are important for maintenance and differentiation of embryonic stem cells and that this at least in part reflects a switch in TCF3 alternative splicing that leads to repression of CDH1/E-cadherin. (PMID:30115631)
• Binding of the hnRNP F to the YAP 3’UTR was demonstrated by Cross-linked RNA Immunoprecipitation. hnRNP F and hnRNP U negatively regulate YAP expression. (PMID:30312683)
• this study is the first to identify hnRNP F/H and K as regulators of Mcl-1 alternative splicing. (PMID:30468106)
• The overexpression of hnRNP-F caused an increase in the stability of Snail1 mRNA. Our RNA chip analysis revealed that hnRNP-F could combine with Snail1 mRNA, and we further demonstrated that hnRNP-F could directly bind to the 3’ untranslated region (3’ UTR) of Snail1 mRNA to enhance its stability. (PMID:31221586)
• Study in thyroid cancer series enriched with poor prognosis cases and found hsa-miR139-5p downregulation as a bona fide poor-prognostic factor. Exogenous hsa-miR-139-5p expression repressed procancer features of thyroid cancer cells. Proteomic analysis revealed that the alternative splicing factor HNRNPF is a putative hsa-miR-139-5p. (PMID:31403184)
• Tyrosine phosphorylation regulates hnRNPA2 granule protein partitioning and reduces neurodegeneration. (PMID:33349959)
• The RNA-binding proteins hnRNP H and F regulate splicing of a MYC-dependent HRAS exon in prostate cancer cells. (PMID:37399401)
• Heterogeneous nuclear ribonucleoprotein F deficiency in mouse podocyte promotes podocytopathy mediated by methyltransferase-like 14 nuclear translocation resulting in Sirtuin 1 gene inhibition. (PMID:38195017)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hnrnpf	ENSMUSG00000042079
rattus_norvegicus	Hnrnpf	ENSRNOG00000014562
drosophila_melanogaster	fus	FBGN0023441
drosophila_melanogaster	glo	FBGN0259139
caenorhabditis_elegans		WBGENE00006367
caenorhabditis_elegans	rbm-12	WBGENE00013703
caenorhabditis_elegans		WBGENE00022253

Paralogs (8): HNRNPH3 (ENSG00000096746), ESRP2 (ENSG00000103067), ESRP1 (ENSG00000104413), HNRNPH2 (ENSG00000126945), GRSF1 (ENSG00000132463), HNRNPH1 (ENSG00000169045), RBM12B (ENSG00000183808), RBM12 (ENSG00000244462)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoprotein F — P52597 (reviewed: P52597)

Alternative names: Nucleolin-like protein mcs94-1

All UniProt accessions (2): P52597, A0A1B0GW42

UniProt curated annotations — full annotation on UniProt →

Function. Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state.

Subunit / interactions. Identified in the spliceosome C complex. Interacts with AGO1, AGO2, TBP and TXNL4/DIM1.

Subcellular location. Nucleus. Nucleoplasm.

Tissue specificity. Expressed ubiquitously.

Post-translational modifications. Sumoylated.

Domain organisation. The N-terminal RRM domains are responsible for recognizing the G-tract of BCL-X RNA.

RefSeq proteins (6): NP_001091674, NP_001091675, NP_001091676, NP_001091677, NP_001091678, NP_004957 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR012996	Znf_CHHC	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050666	ESRP	Family

Pfam: PF00076, PF08080

UniProt features (85 total): strand 21, site 12, modified residue 12, mutagenesis site 12, helix 8, cross-link 6, turn 4, domain 3, region of interest 3, chain 2, initiator methionine 1, sequence variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3TFY	X-RAY DIFFRACTION	2.75
2HGL	SOLUTION NMR
2HGM	SOLUTION NMR
2HGN	SOLUTION NMR
2KFY	SOLUTION NMR
2KG0	SOLUTION NMR
2KG1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52597-F1	65.36	0.01

Functional residue map

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

Catalytic / active sites (12): 20 (interaction with rna); 52 (interaction with rna); 75 (interaction with rna); 116 (interaction with rna); 120 (interaction with rna); 150 (interaction with rna); 173 (interaction with rna); 294 (interaction with rna); 298 (interaction with rna); 326 (interaction with rna); 349 (interaction with rna); 16 (interaction with rna)

Post-translational modifications (18): 1, 2, 104, 107, 161, 187, 193, 195, 200, 215, 224, 265, 72, 87, 167, 185, 200, 224

Mutagenesis-validated functional residues (12):

Position	Phenotype
20	loss of rna-binding.
84	loss of rna-binding.
116	decreases affinity for rna oligonucleotide 100-fold.
120	little disruption of binding rna. decreases affinity for rna oligonucleotide 100-fold. abrogates rna-binding; when assoc
150	no effect on affinity for rna oligonucleotide.
156	drastically effects folding of rrm2.
173	minimal effect on affinity for rna oligonucleotide.
178	little disruption of binding rna.
179	decreases affinity for rna oligonucleotide 100-fold.
180	decreases affinity for rna oligonucleotide 10-fold. abrogates rna-binding; when associated with a-120.
182	decreases affinity for rna oligonucleotide 100-fold.
184	minimal effect on affinity for rna oligonucleotide.

Function

Pathways and Gene Ontology

Reactome pathways

6 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-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

MSigDB gene sets: 227 (showing top): AGGAAGC_MIR5163P, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_SIGNALING_BY_FGFR, MATTIOLI_MGUS_VS_PCL, MAZ_Q6, HSIAO_HOUSEKEEPING_GENES, GGGTGGRR_PAX4_03, EFC_Q6, PUJANA_CHEK2_PCC_NETWORK, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GNF2_XRCC5, GNF2_FBL, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING

GO Biological Process (5): mRNA splicing, via spliceosome (GO:0000398), RNA processing (GO:0006396), regulation of RNA splicing (GO:0043484), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): RNA binding (GO:0003723), single-stranded RNA binding (GO:0003727), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), synapse (GO:0045202), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by FGFR2	1
mRNA Splicing	1
Metabolism of RNA	1
Interleukin-12 signaling	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
cell junction	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
protein-containing complex	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

2084 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPF	HNRNPA2B1	P22626	893
HNRNPF	KHSRP	Q92945	871
HNRNPF	HNRNPDL	O14979	821
HNRNPF	FUBP3	Q96I24	818
HNRNPF	HNRNPA1	P09651	810
HNRNPF	HNRNPC	P07910	806
HNRNPF	HNRNPM	P52272	790
HNRNPF	HNRNPU	Q00839	789
HNRNPF	HNRNPK	P61978	763
HNRNPF	NUCLEOLIN	P19338	756
HNRNPF	HNRNPH1	P31943	749
HNRNPF	FUBP1	Q96AE4	745
HNRNPF	SRSF1	Q07955	742
HNRNPF	SRSF2	Q01130	736
HNRNPF	SRSF3	P23152	729

IntAct

431 interactions, top by confidence:

A	B	Type	Score
HNRNPUL1	HNRNPF	psi-mi:“MI:0915”(physical association)	0.740
HNRNPF	HNRNPUL1	psi-mi:“MI:0915”(physical association)	0.740
HNRNPM	HNRNPF	psi-mi:“MI:0915”(physical association)	0.720
C1orf94	HNRNPF	psi-mi:“MI:0915”(physical association)	0.720
HNRNPF	DZIP3	psi-mi:“MI:0915”(physical association)	0.720
HNRNPF	C1orf94	psi-mi:“MI:0915”(physical association)	0.720
RBFOX2	HNRNPF	psi-mi:“MI:0915”(physical association)	0.670
HNRNPF	RBFOX2	psi-mi:“MI:0915”(physical association)	0.670
HNRNPH1	HNRNPF	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
HNRNPF		psi-mi:“MI:0915”(physical association)	0.560
TLE5	HNRNPF	psi-mi:“MI:0915”(physical association)	0.560
TFG	HNRNPF	psi-mi:“MI:0915”(physical association)	0.560
HSFY1	HNRNPF	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	EIF4ENIF1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	IKZF3	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	TFG	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	HSFY1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (755): HNRNPF (Affinity Capture-MS), HNRNPF (Two-hybrid), HNRNPM (Two-hybrid), DZIP3 (Two-hybrid), TFG (Two-hybrid), HNRNPUL1 (Two-hybrid), IKZF3 (Two-hybrid), RBFOX2 (Two-hybrid), EIF4ENIF1 (Two-hybrid), CCDC33 (Two-hybrid), C1orf94 (Two-hybrid), HSFY1 (Two-hybrid), HNRNPF (Affinity Capture-MS), HNRNPF (Affinity Capture-MS), HNRNPF (Affinity Capture-MS)

ESM2 similar proteins: B2GV05, F1LQ48, O88506, O95747, P09012, P14866, P52597, P52756, P55795, P70333, Q06AA4, Q13148, Q15139, Q1RMU5, Q2KIR1, Q3U0V1, Q3US41, Q58A45, Q5E9J1, Q5R495, Q5R5W2, Q5RD26, Q5ZLN5, Q60HC3, Q62101, Q640Q5, Q66KH9, Q6AY09, Q6DGV1, Q6NXG1, Q6P9R2, Q794E4, Q8C0V0, Q8C854, Q8R081, Q8UVD9, Q8VC70, Q8WVV9, Q91WJ8, Q91YE7

Diamond homologs: A1L1G1, A8WPC5, B2RYD2, B2RYJ8, O35737, P31943, P52597, P55795, P70333, Q12849, Q22708, Q3SZF3, Q3US41, Q5E9J1, Q5RD26, Q5ZLR4, Q60HC3, Q6AY09, Q6DEZ7, Q6NXG1, Q794E4, Q7ZVR8, Q7ZY29, Q8C5Q4, Q8K0G8, Q8R3C6, Q8VHV7, Q9BJZ5, Q9H6T0, Q9Z2X1, P31942, Q9Y4C8, Q15020, Q5REG1, Q9JLI8, Q5RBM8, Q8R4X3, Q8SQ27, Q9NTZ6, Q66JV4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZFP91	“down-regulates quantity”	HNRNPF	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
Neddylation	11	6.2×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA stabilization	6	18.8×	3e-04
intrinsic apoptotic signaling pathway	6	18.4×	3e-04
cellular response to UV	5	12.6×	5e-03
G1/S transition of mitotic cell cycle	7	12.0×	5e-04
protein ubiquitination	12	4.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

498 predictions. Top by Δscore:

Variant	Effect	Δscore
10:43387932:TGTGG:T	acceptor_gain	1.0000
10:43387933:GTGG:G	acceptor_gain	1.0000
10:43387934:TGG:T	acceptor_gain	1.0000
10:43387935:GG:G	acceptor_gain	1.0000
10:43387935:GGC:G	acceptor_loss	1.0000
10:43387937:C:CC	acceptor_gain	1.0000
10:43394624:GCTTA:G	donor_loss	1.0000
10:43394625:CTTAC:C	donor_loss	1.0000
10:43394626:TTACC:T	donor_loss	1.0000
10:43394627:TA:T	donor_loss	1.0000
10:43394628:A:AT	donor_loss	1.0000
10:43394629:CCTT:C	donor_loss	1.0000
10:43396449:GACTT:G	donor_loss	1.0000
10:43396450:ACTT:A	donor_loss	1.0000
10:43396451:CTTAC:C	donor_loss	1.0000
10:43396453:T:TG	donor_loss	1.0000
10:43396454:A:AC	donor_gain	1.0000
10:43396454:A:C	donor_loss	1.0000
10:43396455:C:A	donor_loss	1.0000
10:43396455:C:CC	donor_gain	1.0000
10:43396455:CCA:C	donor_gain	1.0000
10:43394623:AGCTT:A	donor_loss	0.9900
10:43394685:TGTC:T	acceptor_gain	0.9900
10:43394689:C:CC	acceptor_gain	0.9900
10:43394130:TG:T	donor_gain	0.9800
10:43394686:GTCC:G	acceptor_loss	0.9800
10:43394687:TCCTA:T	acceptor_loss	0.9800
10:43394688:CCTA:C	acceptor_loss	0.9800
10:43394689:C:CA	acceptor_loss	0.9800
10:43395868:AAG:A	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000104704 (10:43406951 G>A), RS1000173525 (10:43396501 G>A), RS1000176332 (10:43404952 G>C), RS1000274732 (10:43401218 A>ACCAT), RS1000335546 (10:43408117 C>T), RS1000356805 (10:43388136 T>C), RS1000512487 (10:43397435 C>T), RS1000606036 (10:43397621 C>G,T), RS1000628379 (10:43410176 C>T), RS1000788108 (10:43403555 T>C,G), RS1000817262 (10:43388044 G>A,C), RS1001081158 (10:43396968 G>A,C,T), RS1001162828 (10:43395586 G>A,T), RS1001298833 (10:43395824 C>T), RS1001329517 (10:43406669 G>A)

Disease associations

OMIM: gene MIM:601037 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009312_4	Antisaccade task score	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007969	cognitive inhibition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523238 (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
6.46	Kd	349.4	nM	CHEMBL5653589
6.46	ED50	349.4	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 11 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148530: Binding affinity to human HNRNPF incubated for 45 mins by Kinobead based pull down assay	kd	0.3494	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	3
Valproic Acid	decreases expression, decreases methylation	3
cobaltous chloride	decreases expression	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
Caffeine	affects phosphorylation, decreases expression	2
Doxorubicin	affects expression, increases expression	2
Metribolone	affects binding, increases reaction, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
quinomethionate	affects expression	1
deoxynivalenol	increases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases reaction, decreases expression	1
sulforaphane	affects binding	1
butylidenephthalide	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
nivalenol	increases expression	1
epigallocatechin gallate	decreases expression	1
phenethyl isothiocyanate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
acyline	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
LDN 193189	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Decitabine	increases expression	1
Arsenic	decreases expression, increases abundance	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
CHEMBL4341427	Binding	Binding affinity to HNRNPF in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis relative to untreated control	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Clinical trials (associated diseases)

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