PTBP1

Summary

PTBP1 (polypyrimidine tract binding protein 1, HGNC:9583) is a protein-coding gene on chromosome 19p13.3, encoding Polypyrimidine tract-binding protein 1 (P26599). Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. It is a selective cancer dependency (DepMap: 50.7% of 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 four repeats of quasi-RNA recognition motif (RRM) domains that bind RNAs. This protein binds to the intronic polypyrimidine tracts that requires pre-mRNA splicing and acts via the protein degradation ubiquitin-proteasome pathway. It may also promote the binding of U2 snRNP to pre-mRNAs. This protein is localized in the nucleoplasm and it is also detected in the perinucleolar structure. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 5725 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 127 total — 10 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 50.7% of screened cell lines
• MANE Select transcript: NM_002819

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9583
Approved symbol	PTBP1
Name	polypyrimidine tract binding protein 1
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HNRPI, HNRNP-I, PTB2, PTB3, PTB-1, PTB4, pPTB
Ensembl gene	ENSG00000011304
Ensembl biotype	protein_coding
OMIM	600693
Entrez	5725

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 21 protein_coding, 8 retained_intron, 4 nonsense_mediated_decay

ENST00000349038, ENST00000350092, ENST00000356948, ENST00000394601, ENST00000585535, ENST00000585856, ENST00000585932, ENST00000585956, ENST00000586481, ENST00000586944, ENST00000587136, ENST00000587191, ENST00000589575, ENST00000589883, ENST00000590887, ENST00000592113, ENST00000592804, ENST00000621737, ENST00000627714, ENST00000635647, ENST00000676227, ENST00000677277, ENST00000677717, ENST00000679114, ENST00000893849, ENST00000893850, ENST00000893851, ENST00000893852, ENST00000893853, ENST00000893854, ENST00000893855, ENST00000893856, ENST00000893857

RefSeq mRNA: 4 — MANE Select: NM_002819 NM_001411140, NM_002819, NM_031990, NM_031991

CCDS: CCDS32859, CCDS42456, CCDS45892, CCDS92475

Canonical transcript exons

ENST00000356948 — 15 exons

Exon	Start	End
ENSE00000464365	806408	806556
ENSE00000892219	807869	807902
ENSE00001250599	805492	805569
ENSE00002798271	810694	812312
ENSE00002937627	797452	797505
ENSE00003474534	804532	804702
ENSE00003543217	799413	799443
ENSE00003566523	808360	808452
ENSE00003574135	804036	804208
ENSE00003596168	810543	810620
ENSE00003632946	804292	804438
ENSE00003671876	805013	805187
ENSE00003721172	803561	803636
ENSE00003735118	804829	804939
ENSE00003788382	808546	808762

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 191.6028 / max 1060.1560, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172750	126.2332	1823
172749	63.2190	1821
172752	1.0050	646
172756	0.7223	398
172754	0.4232	183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	98.80	gold quality
cervix squamous epithelium	UBERON:0006922	98.76	gold quality
nipple	UBERON:0002030	98.45	gold quality
pharyngeal mucosa	UBERON:0000355	98.40	gold quality
stromal cell of endometrium	CL:0002255	98.39	gold quality
penis	UBERON:0000989	98.36	gold quality
pancreatic ductal cell	CL:0002079	98.31	gold quality
islet of Langerhans	UBERON:0000006	98.16	gold quality
pylorus	UBERON:0001166	98.16	gold quality
caecum	UBERON:0001153	98.11	gold quality
ventricular zone	UBERON:0003053	98.07	gold quality
metanephros cortex	UBERON:0010533	98.07	gold quality
trachea	UBERON:0003126	98.04	gold quality
right uterine tube	UBERON:0001302	98.03	gold quality
embryo	UBERON:0000922	98.02	gold quality
vermiform appendix	UBERON:0001154	98.02	gold quality
ileal mucosa	UBERON:0000331	98.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.94	gold quality
endometrium epithelium	UBERON:0004811	97.92	gold quality
skin of leg	UBERON:0001511	97.89	gold quality
right lobe of thyroid gland	UBERON:0001119	97.88	gold quality
oviduct epithelium	UBERON:0004804	97.85	gold quality
skin of abdomen	UBERON:0001416	97.84	gold quality
renal medulla	UBERON:0000362	97.83	gold quality
left lobe of thyroid gland	UBERON:0001120	97.83	gold quality
lymph node	UBERON:0000029	97.82	gold quality
spleen	UBERON:0002106	97.79	gold quality
thyroid gland	UBERON:0002046	97.74	gold quality
fallopian tube	UBERON:0003889	97.74	gold quality
upper lobe of left lung	UBERON:0008952	97.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6819	no	278.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, HNRNPK, MYC, NR1H2, TXK

miRNA regulators (miRDB)

102 targeting PTBP1, 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-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 50.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Nucleocytoplasmic shuttling of polypyrimidine tract-binding protein is uncoupled from RNA export (PMID:11739782)
• PTB NES is a functionally important domain of this multifunctional protein that utilizes an unknown export receptor. (PMID:11781313)
• chemical shift mapping of RNA interactions with the polypyrimidine tract binding protein (PMID:11788707)
• translation of some IRES-containing mRNAs is regulated by proteolytic cleavage of PTB during apoptosis (PMID:12004072)
• resonance assignment and topology of the 2H, 13C, 15N labelled 29 kDa N-terminal fragment (PMID:12449425)
• PTB has been identified as a component of the putative complex involved in regulating the stability of CD154 mRNA at late times of T cell activation. (PMID:12517964)
• Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins and plays a role in spliceosome assembly (PMID:12581738)
• unr and nPTB act as RNA chaperones by changing the structure of the IRES into one that permits translation initiation (PMID:12667457)
• nucleo-cytoplasmic transport of PTB is regulated by the 3’,5’-cAMP-dependent protein kinase (PKA) (PMID:12851456)
• Strong upregulation of PTB expression in tumor cells of glial or primitive neuroectodermal origin suggests involvement of this protein in cellular transformation. (PMID:14769134)
• The interactions of PTB-1 and PCBP1 with their cognate binding sites on the Bag-1 IRES disrupt many of the RNA-RNA interactions, and this creates a largely unstructured region of approximately 40 nucleotides that could permit ribosome binding. (PMID:15169918)
• Data show that RNA recognition motifs (RRMs) 1 and 2 of polypyrimidine tract binding protein (PTB) contribute to RNA binding and that full-length PTB is monomeric, with an elongated structure consistent with a linear arrangement of RRMs. (PMID:15341728)
• investigated the role of PTB for hepatitis C virus (HCV) translation, replication and chronic HCV infection; PTB inhibits HCV IRES-mediated translation but data do not indicate a significant role of PTB for HCV replication and chronic HCV infection (PMID:15669107)
• upstream element in human papillomavirus type 16 interacted specifically with CstF-64, hnRNP C1/C2 & polypyrimidine tract binding protein, suggesting these factors were enhancing or regulating polyadenylation at the HPV-16 early polyadenylation signal (PMID:15767428)
• solution structures of the four RNA binding domains (RBDs) of PTB; found that PTB is both a sequence-specific RNA binding protein with a preference for CU tracts and an RNA remodeler with an ability to bring separated pyrimidine tracts into proximity (PMID:16179478)
• analysis of the splicing repressor domain in polypyrimidine tract-binding protein (PMID:16282332)
• The polypyrimidine tract binding protein is a monomer. (PMID:16314454)
• The structure of the two C-terminal RNA recognition motifs (RRM3 and RRM4) of PTB was studied. (PMID:16362043)
• Small-angle X-ray scattering to determine the low-resolution structure of the entire PTB was used. (PMID:16765895)
• Data showed that polypyrimidine tract binding protein PTB, a known IRES trans-acting factor or ITAF, is pivotal in regulating the apoptotic process by controlling IRES function. (PMID:16885029)
• Obtained results do give insights into PTB’s affinity for different RNA sequences. The low-energy conformations of the complexes provided information about the mechanism of binding. The analysis showed that binding is not RNA sequence-specific (PMID:17497933)
• Identification of PSF, p54(nrb), PTB, and U1A as proteins specifically bound to the COX-2 polyadenylation signal upstream sequence elements . (PMID:17507659)
• The results are consistent with a repressive mechanism in which cooperative binding of PTB to the PPT competes with binding of U2AF, thereby specifically blocking splicing of the alpha-actinin SM exon. (PMID:17592047)
• Improved segmental isotope labeling methods for the NMR study of multidomain large proteins: application to RNP L. (PMID:17936301)
• Under polypyrimidine tract binding protein-mediated repression, assembly was arrested at an A-like complex that was unable to transition to spliceosomal complexes. (PMID:18193060)
• overexpression of polypyrimidine tract binding protein (PTB) induces HPV-16 late gene expression in cells transfected with subgenomic HPV-16 plasmids or with full-length HPV-16 genomes and in persistently HPV-16-infected cells. (PMID:18216120)
• results provide a striking illustration of the importance of mRNA codon content in determining levels of PTB protein expression, even within cells of the natural host species (PMID:18335065)
• PTB is not oncogenic and can either promote or antagonize a malignant trait dependent upon the specific intra-cellular environment (PMID:18499661)
• in response to cellular activation in T cells and B cells, a PTB-containing stability complex forms that contains binding sites for Rab8A and cyclin D(2) transcripts and increases their mRNA half-lifes (PMID:18714005)
• polypyrimidine tract binding protein inhibits HCMV replication by interfering with major immediate-early (MIE) gene splicing through competition with U2AF for binding to the polypyrimidine tract in MIE gene introns. (PMID:19144709)
• Since it can bind to short and long polypyrimidine tracts, structured or single-stranded, PTB takes on the role of a versatile adaptor protein that facilitates formation of mRNA-protein regulatory complexes. (PMID:19226116)
• This is the first study that enlightens the interaction of DENV NS4A protein with PTB, in addition to demonstrating the novel role of PTB in relation to mosquito-borne flavivirus life-cycle. (PMID:19450550)
• PTB1 overexpression in cardiomyocytes induced caspase activity and caspase-dependent DNA fragmentation during ischemia, which is otherwise caspase-independent in differentiated cardiomyocytes. (PMID:19590510)
• The combined results suggest that 3C-mediated cleavage of PTB might be involved in down-regulation of viral translation to give way to subsequent viral genome replication. (PMID:19889140)
• Data suggest a mechanism for PTB to modulate splice site competition to produce opposite functional consequences, which may be generally applicable to RNA-binding splicing factors to regulate alternative splicing in mammalian cells. (PMID:20064465)
• It appears that the polypyrimidine tract-binding protein might help in circularization of the coxsackievirus B3 RNA by bridging the ends necessary for efficient translation of the viral RNA. (PMID:20071487)
• The slow backbone dynamics of PTB1:34, induced by packing of (RNA recognition motifs) RRM3 and RRM4, could be essential for high-affinity binding to a flexible polypyrimidine tract RNA and also provide entropic compensation for its own formation. (PMID:20080103)
• a strong correlation between the expression of PTB-1, YB-1 and c-myc in multiple myeloma-derived cell lines (PMID:20190818)
• PTBP1 regulates the alternative splicing of dopamine D2 receptor. (PMID:21054383)
• Differentially modified PTB regulates CD40L expression at multiple steps by retaining CD40L mRNA in the nucleus, directly regulating mRNA stability at late times of activation, and forming a ribonuclear complex. (PMID:21242519)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptbp1a	ENSDARG00000019362
danio_rerio	ptbp1b	ENSDARG00000031907
mus_musculus	Ptbp1	ENSMUSG00000006498
rattus_norvegicus	Ptbp1	ENSRNOG00000010448
rattus_norvegicus	Ptbp1-ps3	ENSRNOG00000070516
drosophila_melanogaster	heph	FBGN0011224
caenorhabditis_elegans		WBGENE00004207

Paralogs (5): HNRNPL (ENSG00000104824), PTBP2 (ENSG00000117569), PTBP3 (ENSG00000119314), HNRNPLL (ENSG00000143889), RBM20 (ENSG00000203867)

Protein

Protein identifiers

Polypyrimidine tract-binding protein 1 — P26599 (reviewed: P26599)

Alternative names: 57 kDa RNA-binding protein PPTB-1, Heterogeneous nuclear ribonucleoprotein I

All UniProt accessions (14): P26599, A0A087WTS6, A0A087WU68, A0A087WUW5, A0A0D9SF20, A0A0U1RRM4, A0A6Q8PEX4, A0A7I2V4H6, A0A7I2V621, A6NLN1, K7EK45, K7EKJ7, K7ELW5, K7ES59

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10. Binds to polypyrimidine-rich controlling element (PCE) of CFTR and promotes exon skipping of CFTR exon 9, thereby antagonizing TIA1 and its role in exon inclusion of CFTR exon 9. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to a polypyrimidine tract flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. In case of infection by picornaviruses, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation.

Subunit / interactions. Monomer. Part of a ternary complex containing KHSRP, PTBP1, PTBP2 and HNRPH1. Interacts with RAVER1 and SFPQ. Interacts with IVNS1ABP (via BACK domain); the interaction is direct.

Subcellular location. Nucleus.

Isoforms (3)

UniProt ID	Names	Canonical?
P26599-3	1	yes
P26599-1	2
P26599-2	3, PTB2

RefSeq proteins (4): NP_001398069, NP_002810, NP_114367, NP_114368 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR006536	HnRNP-L/PTB	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR021790	PTBP1-like_RRM2	Domain
IPR035000	PTBP1_RRM1	Domain
IPR035001	PTBP1_RRM3	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR055204	HNRNPL_RRM	Domain

Pfam: PF11835, PF13893, PF22976

UniProt features (62 total): strand 29, helix 13, modified residue 6, turn 5, domain 4, cross-link 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3ZZY	X-RAY DIFFRACTION	1.4
3ZZZ	X-RAY DIFFRACTION	1.55
9LGQ	X-RAY DIFFRACTION	1.82
8BWF	X-RAY DIFFRACTION	2.9
1QM9	SOLUTION NMR
1SJQ	SOLUTION NMR
1SJR	SOLUTION NMR
2AD9	SOLUTION NMR
2ADB	SOLUTION NMR
2ADC	SOLUTION NMR
2EVZ	SOLUTION NMR
2N3O	SOLUTION NMR
8BGF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26599-F1	72.18	0.19

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 (8): 459, 65, 218, 1, 16, 127, 138, 141

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: 278 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_SNRP70, REACTOME_SIGNALING_BY_FGFR, MORF_UBE2I, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, MORF_HDAC1, GOBP_NEUROGENESIS, RIZKI_TUMOR_INVASIVENESS_3D_DN, GNF2_MCM5, PRAMOONJAGO_SOX4_TARGETS_DN, YY1_Q6, MODULE_503

GO Biological Process (15): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), RNA splicing (GO:0008380), neurogenesis (GO:0022008), negative regulation of RNA splicing (GO:0033119), regulation of RNA splicing (GO:0043484), regulation of cell differentiation (GO:0045595), negative regulation of neuron differentiation (GO:0045665), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of mRNA splicing, via spliceosome (GO:0048025), negative regulation of muscle cell differentiation (GO:0051148), positive regulation of calcineurin-NFAT signaling cascade (GO:0070886), IRES-dependent viral translational initiation (GO:0075522), gene expression (GO:0010467), negative regulation of mRNA metabolic process (GO:1903312)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), poly-pyrimidine tract binding (GO:0008187), pre-mRNA binding (GO:0036002), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), membrane (GO:0016020), extracellular exosome (GO:0070062)

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
regulation of mRNA splicing, via spliceosome	2
RNA processing	2
mRNA metabolic process	2
cell differentiation	2
RNA splicing	2
negative regulation of cell differentiation	2
RNA binding	2
binding	2
nuclear lumen	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
nervous system development	1
negative regulation of gene expression	1
regulation of RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
regulation of developmental process	1
regulation of cellular process	1
neuron differentiation	1
regulation of neuron differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
mRNA splicing, via spliceosome	1
negative regulation of RNA splicing	1
negative regulation of mRNA processing	1
muscle cell differentiation	1
regulation of muscle cell differentiation	1
calcineurin-NFAT signaling cascade	1
regulation of calcineurin-NFAT signaling cascade	1
positive regulation of calcineurin-mediated signaling	1
viral process	1
viral translation	1
macromolecule biosynthetic process	1
negative regulation of RNA metabolic process	1
regulation of mRNA metabolic process	1
nucleic acid binding	1
single-stranded RNA binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTBP1	HNRNPC	P07910	982
PTBP1	HNRNPK	P61978	974
PTBP1	HNRNPA2B1	P22626	944
PTBP1	HNRNPA1	P09651	936
PTBP1	HNRNPDL	O14979	929
PTBP1	HNRNPH1	P31943	895
PTBP1	SRSF1	Q07955	892
PTBP1	MORF4L1	Q9UBU8	882
PTBP1	NUCLEOLIN	P19338	877
PTBP1	PKM	P14618	877
PTBP1	HNRNPM	P52272	876
PTBP1	CELF1	Q92879	862
PTBP1	RAVER1	Q8IY67	861
PTBP1	TARDBP	Q13148	853
PTBP1	HNRNPL	P14866	842

IntAct

222 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
PTBP1	SNRPA	psi-mi:“MI:0915”(physical association)	0.800
SNRPA	PTBP1	psi-mi:“MI:0915”(physical association)	0.800
PTBP1	CFTR	psi-mi:“MI:0407”(direct interaction)	0.750
MED19	MED19	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
PTBP1	SFPQ	psi-mi:“MI:0915”(physical association)	0.700
SFPQ	PTBP1	psi-mi:“MI:0915”(physical association)	0.700
RBM10	PTBP1	psi-mi:“MI:0915”(physical association)	0.670
PTBP1	RBM10	psi-mi:“MI:0915”(physical association)	0.670
PTBP1	hnrnpab.L	psi-mi:“MI:0915”(physical association)	0.640
hnrnpab.L	PTBP1	psi-mi:“MI:0407”(direct interaction)	0.640
hnrnpab.L	PTBP1	psi-mi:“MI:0914”(association)	0.640
hnrnpab.L	PTBP1	psi-mi:“MI:0216”(palmitoylation reaction)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640

BioGRID (625): PTBP1 (Reconstituted Complex), PTBP1 (Reconstituted Complex), SFPQ (Affinity Capture-Western), PTBP1 (Two-hybrid), SNRPA (Two-hybrid), PTBP1 (Affinity Capture-RNA), PTBP1 (Affinity Capture-RNA), PTBP1 (Affinity Capture-RNA), PTBP1 (Protein-peptide), PTBP1 (Affinity Capture-MS), PTBP1 (Affinity Capture-MS), PTBP1 (Affinity Capture-MS), PTBP1 (Affinity Capture-MS), PTBP1 (Affinity Capture-MS), PTBP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IEW8, A4QNI8, B5DF91, O01671, O09032, O17310, O61374, O64380, O95758, O97018, P16914, P19339, P26378, P26599, P42731, P70372, P86049, Q12926, Q14576, Q15717, Q1JQ73, Q24668, Q28FX0, Q28GD4, Q29099, Q5R9H4, Q5R9Z6, Q5U259, Q5YD48, Q60899, Q60900, Q61701, Q6DEY7, Q6GLB5, Q6GR16, Q6YZW2, Q7SZT7, Q8CH84, Q8GZ26, Q8LFS6

Diamond homologs: E9PT37, O95758, P0DW16, P17225, P26599, Q00438, Q14966, Q29099, Q3UQS8, Q5T481, Q61464, Q66H20, Q8BHD7, Q8WN55, Q91Z31, Q9FGL9, Q9UKA9, Q9ULV3, Q9Z118, A1A6K6, O59784, O74452, P34761, P45429, Q07655, Q8VXZ9, P40567, P43243, P43244, Q15233, Q5FVM4, Q5RFL9, Q6ICX4, Q8K310, Q99K48, Q9MAC5, A2Y0J7, B8AM21, O22922, O74968

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PTBP1	up-regulates	Alternative_Splicing_Regulation
MYC	“up-regulates quantity by expression”	PTBP1	“transcriptional regulation”
RAVER1	“up-regulates activity”	PTBP1	binding
PRKACA	“down-regulates activity”	PTBP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
Processing of Capped Intron-Containing Pre-mRNA	12	8.9×	7e-06
mRNA Splicing - Major Pathway	13	6.4×	4e-05
mRNA Polyadenylation	8	6.3×	4e-03
Dengue Virus-Host Interactions	11	4.5×	4e-03
Viral Infection Pathways	14	3.9×	3e-03
Infectious disease	17	3.8×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA stabilization	7	19.0×	2e-05
autophagosome maturation	6	15.6×	4e-04
positive regulation of transcription elongation by RNA polymerase II	6	13.4×	7e-04
intrinsic apoptotic signaling pathway	5	13.3×	2e-03
mitophagy	5	11.8×	4e-03
circadian rhythm	6	10.8×	1e-03
negative regulation of translation	7	10.2×	7e-04
positive regulation of translation	6	10.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	0
Uncertain significance	64
Likely benign	14
Benign	8

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1210056	NM_002819.5(PTBP1):c.1A>G (p.Met1Val)	Pathogenic
1706510	GRCh37/hg19 19p13.3(chr19:260911-2256387)x3	Pathogenic
4446973	NM_002819.5(PTBP1):c.41G>A (p.Arg14Gln)	Pathogenic
4528347	NM_002819.5(PTBP1):c.1A>C (p.Met1Leu)	Pathogenic
4528348	NM_002819.5(PTBP1):c.2T>G (p.Met1Arg)	Pathogenic
4528349	NM_002819.5(PTBP1):c.2T>A (p.Met1Lys)	Pathogenic
4528350	NM_002819.5(PTBP1):c.3G>C (p.Met1Ile)	Pathogenic
4528352	NM_002819.5(PTBP1):c.137A>C (p.Lys46Thr)	Pathogenic
4528353	NM_002819.5(PTBP1):c.144A>T (p.Lys48Asn)	Pathogenic
828191	NM_002819.5(PTBP1):c.2T>C (p.Met1Thr)	Pathogenic

SpliceAI

2644 predictions. Top by Δscore:

Variant	Effect	Δscore
19:797504:GG:G	donor_gain	1.0000
19:797504:GGGTG:G	donor_loss	1.0000
19:797505:GG:G	donor_gain	1.0000
19:797505:GGTG:G	donor_loss	1.0000
19:799441:AAGGT:A	donor_loss	1.0000
19:799442:AGGTA:A	donor_loss	1.0000
19:799445:T:A	donor_loss	1.0000
19:804032:TCA:T	acceptor_loss	1.0000
19:804033:CA:C	acceptor_loss	1.0000
19:804034:A:AG	acceptor_gain	1.0000
19:804034:AGC:A	acceptor_loss	1.0000
19:804035:G:A	acceptor_loss	1.0000
19:804035:G:GA	acceptor_gain	1.0000
19:804035:GCAA:G	acceptor_gain	1.0000
19:804037:AAACG:A	acceptor_gain	1.0000
19:804140:G:GT	donor_gain	1.0000
19:804140:G:T	donor_gain	1.0000
19:804206:CAGG:C	donor_loss	1.0000
19:804207:AGG:A	donor_loss	1.0000
19:804208:GG:G	donor_loss	1.0000
19:804209:G:C	donor_loss	1.0000
19:804210:T:G	donor_loss	1.0000
19:804289:CAG:C	acceptor_loss	1.0000
19:804290:A:AG	acceptor_gain	1.0000
19:804291:G:GG	acceptor_gain	1.0000
19:804436:GCG:G	donor_gain	1.0000
19:804439:G:GG	donor_gain	1.0000
19:804439:G:T	donor_loss	1.0000
19:804440:T:A	donor_loss	1.0000
19:804527:CACA:C	acceptor_loss	1.0000

AlphaMissense

3658 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:804098:G:A	V60M	1.000
19:804099:T:A	V60E	1.000
19:804104:C:G	H62D	1.000
19:804106:C:A	H62Q	1.000
19:804106:C:G	H62Q	1.000
19:804111:G:C	R64P	1.000
19:804155:G:A	G79R	1.000
19:804155:G:C	G79R	1.000
19:804155:G:T	G79W	1.000
19:804156:G:A	G79E	1.000
19:804164:T:C	F82L	1.000
19:804166:T:A	F82L	1.000
19:804166:T:G	F82L	1.000
19:804167:G:A	G83R	1.000
19:804167:G:C	G83R	1.000
19:804167:G:T	G83W	1.000
19:804168:G:A	G83E	1.000
19:804168:G:T	G83V	1.000
19:804174:T:A	V85D	1.000
19:804183:T:C	L88P	1.000
19:804186:T:A	L89Q	1.000
19:804186:T:C	L89P	1.000
19:804192:T:C	L91P	1.000
19:804207:A:C	Q96P	1.000
19:804208:G:C	Q96H	1.000
19:804208:G:T	Q96H	1.000
19:804292:G:C	A97P	1.000
19:804293:C:A	A97D	1.000
19:804295:T:C	F98L	1.000
19:804296:T:C	F98S	1.000

dbSNP variants (sampled 300 via entrez): RS1000114324 (19:809123 C>G,T), RS1000134725 (19:801055 C>T), RS1000207392 (19:797705 C>G,T), RS1000299135 (19:797187 T>C), RS1000399502 (19:807171 C>T), RS1000471646 (19:805794 G>A,C), RS1000509551 (19:801956 C>T), RS1000555434 (19:798812 C>G,T), RS1000734143 (19:809799 T>A,G), RS1000808315 (19:805054 G>A), RS1000898641 (19:801258 G>C), RS1000965163 (19:798199 G>T), RS1001272863 (19:797435 T>C), RS1001427875 (19:798470 G>A), RS1001457021 (19:806238 T>C,G)

Disease associations

OMIM: gene MIM:600693 | disease phenotypes: MIM:621495

GenCC curated gene-disease

Mondo (1): STAD syndrome (MONDO:0980973)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004604_37	Hematocrit	2.000000e-18
GCST004615_118	Hemoglobin concentration	5.000000e-14
GCST009724_73	Vertical cup-disc ratio (multi-trait analysis)	1.000000e-13
GCST010002_145	Refractive error	1.000000e-11
GCST90002383_91	Hematocrit	3.000000e-25
GCST90002383_92	Hematocrit	5.000000e-16
GCST90002384_439	Hemoglobin	4.000000e-24
GCST90002384_440	Hemoglobin	2.000000e-13
GCST90002389_254	Lymphocyte percentage of white cells	5.000000e-10
GCST90002403_340	Red blood cell count	7.000000e-23
GCST90011898_63	Alanine aminotransferase levels	3.000000e-08
GCST90013663_60	Alanine aminotransferase levels	2.000000e-10
GCST90013664_90	Aspartate aminotransferase levels	4.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293230 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,611 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL964	DISULFIRAM	4	38,611

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

ChEMBL bioactivities

123 potent at pChembl≥5 of 310 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.45	Potency	35.5	nM	CHEMBL1363984
6.95	Potency	112.2	nM	CHEMBL1594943
6.75	Potency	177.8	nM	CHEMBL1452461
6.55	Potency	281.8	nM	CHEMBL3391713
6.55	Potency	281.8	nM	CHEMBL1413518
6.35	Potency	446.7	nM	CHEMBL1439171
6.25	Potency	562.3	nM	CHEMBL1486095
6.20	Potency	631	nM	CHEMBL1442022
6.10	Potency	794.3	nM	CHEMBL1305276
6.10	Potency	794.3	nM	CHEMBL1428112
6.05	Potency	891.3	nM	CHEMBL455284
6.00	Potency	1000	nM	CHEMBL1347831
5.90	Potency	1259	nM	CHEMBL1582535
5.80	Potency	1585	nM	CHEMBL1582535
5.75	Potency	1778	nM	CHEMBL1562876
5.70	Potency	1995	nM	CHEMBL3199467
5.70	Potency	1995	nM	CHEMBL1433302
5.70	Potency	1995	nM	CHEMBL3191023
5.65	Potency	2239	nM	CHEMBL1466050
5.60	Potency	2512	nM	CHEMBL1453489
5.60	Potency	2512	nM	CHEMBL3193835
5.60	Potency	2512	nM	CHEMBL1320641
5.55	Potency	2818	nM	CHEMBL2095095
5.51	Kd	3122	nM	CHEMBL3752910
5.51	ED50	3122	nM	CHEMBL3752910
5.50	Potency	3162	nM	CHEMBL3190557
5.50	Potency	3162	nM	CHEMBL3190181
5.50	Potency	3162	nM	CHEMBL1456425
5.50	Potency	3162	nM	CHEMBL3194167
5.50	Potency	3162	nM	CHEMBL3198912
5.50	Potency	3162	nM	CHEMBL1489856
5.50	Potency	3162	nM	CHEMBL1483754
5.45	Potency	3548	nM	CHEMBL3196451
5.40	Potency	3981	nM	CHEMBL3198912
5.40	Potency	3981	nM	CHEMBL1320641
5.40	Potency	3981	nM	CHEMBL1596871
5.40	Potency	3981	nM	CHEMBL1520067
5.40	Potency	3981	nM	DISULFIRAM
5.40	Potency	3981	nM	CHEMBL1407693
5.40	Potency	3981	nM	CHEMBL1545760
5.40	Potency	3981	nM	CHEMBL1312676
5.40	Potency	3981	nM	CHEMBL1353865
5.40	Potency	3981	nM	CHEMBL3195746
5.35	Potency	4467	nM	CHEMBL1498509
5.35	Potency	4467	nM	CHEMBL1412578
5.35	Potency	4467	nM	CHEMBL1524804
5.35	Potency	4467	nM	CHEMBL1312676
5.35	Potency	4467	nM	CHEMBL1353865
5.35	Potency	4467	nM	CHEMBL1506271
5.35	Potency	4467	nM	CHEMBL1451774

PubChem BioAssay actives

1 with measured affinity, of 10 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	2149141: Binding affinity to human PTBP1 incubated for 45 mins by Kinobead based pull down assay	kd	3.1217	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression	4
bisphenol A	decreases expression	3
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Arsenic	increases abundance, increases expression, increases methylation	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, decreases expression, affects localization	1
cobaltous chloride	decreases expression	1
cadmium acetate	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
AM 251	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Bortezomib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Vehicle Emissions	increases abundance, decreases expression	1
Cisplatin	decreases expression	1
Copper	affects binding, decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 7 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614037	Functional	PUBCHEM_BIOASSAY: High Content Assay for Compounds that inhibit the Assembly of the Perinucleolar Compartment: Confirmation of PNC Inhibition. (Class of assay: confirmatory) [Related pubchem assays: 2431 (Summary assay), 2417 (Primary scree	PubChem BioAssay data set
CHEMBL5652183	Binding	Binding affinity to human PTBP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2CK	Abcam HeLa PTBP1 KO	Cancer cell line	Female
CVCL_E0M3	Ubigene HeLa PTBP1 KO	Cancer cell line	Female
CVCL_TH41	HAP1 PTBP1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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