PCBP1

Summary

PCBP1 (poly(rC) binding protein 1, HGNC:8647) is a protein-coding gene on chromosome 2p13.3, encoding Poly(rC)-binding protein 1 (Q15365). Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. It is a common-essential gene (DepMap: required in 97.8% of cancer cell lines).

This intronless gene is thought to have been generated by retrotransposition of a fully processed PCBP-2 mRNA. This gene and PCBP-2 have paralogues (PCBP3 and PCBP4) which are thought to have arisen as a result of duplication events of entire genes. The protein encoded by this gene appears to be multifunctional. It along with PCBP-2 and hnRNPK corresponds to the major cellular poly(rC)-binding protein. It contains three K-homologous (KH) domains which may be involved in RNA binding. This encoded protein together with PCBP-2 also functions as translational coactivators of poliovirus RNA via a sequence-specific interaction with stem-loop IV of the IRES and promote poliovirus RNA replication by binding to its 5’-terminal cloverleaf structure. It has also been implicated in translational control of the 15-lipoxygenase mRNA, human Papillomavirus type 16 L2 mRNA, and hepatitis A virus RNA. The encoded protein is also suggested to play a part in formation of a sequence-specific alpha-globin mRNP complex which is associated with alpha-globin mRNA stability.

Source: NCBI Gene 5093 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 16 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• Cancer dependency (DepMap): dependent in 97.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006196

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8647
Approved symbol	PCBP1
Name	poly(rC) binding protein 1
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HNRPE1, hnRNP-E1, HNRPX, hnRNP-X
Ensembl gene	ENSG00000169564
Ensembl biotype	protein_coding
OMIM	601209
Entrez	5093

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000303577

RefSeq mRNA: 1 — MANE Select: NM_006196 NM_006196

CCDS: CCDS1898

Canonical transcript exons

ENST00000303577 — 1 exons

Exon	Start	End
ENSE00001129885	70087477	70089203

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 275.8696 / max 3109.9879, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20828	243.1674	1828
20827	14.9043	1809
20829	14.1359	1788
20826	3.6619	961

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.39	gold quality
gastrocnemius	UBERON:0001388	99.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.21	gold quality
muscle of leg	UBERON:0001383	99.19	gold quality
endometrium epithelium	UBERON:0004811	99.15	gold quality
granulocyte	CL:0000094	99.13	gold quality
right adrenal gland	UBERON:0001233	99.13	gold quality
popliteal artery	UBERON:0002250	99.12	gold quality
tibial artery	UBERON:0007610	99.12	gold quality
monocyte	CL:0000576	99.09	gold quality
leukocyte	CL:0000738	99.09	gold quality
right adrenal gland cortex	UBERON:0035827	99.09	gold quality
mononuclear cell	CL:0000842	99.07	gold quality
left adrenal gland	UBERON:0001234	99.06	gold quality
ganglionic eminence	UBERON:0004023	99.06	gold quality
aorta	UBERON:0000947	99.02	gold quality
right coronary artery	UBERON:0001625	98.99	gold quality
descending thoracic aorta	UBERON:0002345	98.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.98	gold quality
left adrenal gland cortex	UBERON:0035825	98.98	gold quality
tibialis anterior	UBERON:0001385	98.97	gold quality
right lung	UBERON:0002167	98.97	gold quality
left uterine tube	UBERON:0001303	98.96	gold quality
left coronary artery	UBERON:0001626	98.95	gold quality
omental fat pad	UBERON:0010414	98.94	gold quality
peritoneum	UBERON:0002358	98.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.93	gold quality
thoracic aorta	UBERON:0001515	98.92	gold quality
body of uterus	UBERON:0009853	98.92	gold quality
ectocervix	UBERON:0012249	98.92	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	1507.09
E-GEOD-100618	no	629.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFCP2, ZBTB17

miRNA regulators (miRDB)

65 targeting PCBP1, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-466	99.67	70.85	2863

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The binding of HuR, CP1, and CP2 to AR mRNA suggests a role for each of these proteins in the post-transcriptional regulation of AR expression in cancer cells. (PMID:12011088)
• PCBP1, a highly homologous isoform of PCBP2, binds to poliovirus stem-loop I with an affinity similar to that of PCBP2 (PMID:12414943)
• The 3’-untranslated region of p21WAF1 mRNA is a composite cis-acting sequence bound by RNA-binding proteins from breast cancer cells, including this one. (PMID:12431987)
• HADHB trifunctional enzyme, human renin, and poly(C)-binding protein are novel renin mRNA-binding proteins that target a cis-element in the 3’-UTR of renin mRNA and regulate renin production (PMID:12933794)
• deletion of NLS I from alphaCP1 blocks its nuclear accumulation, whereas NLS I and NLS II must both be inactivated to block nuclear accumulation of alphaCP2 (PMID:14612387)
• 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)
• Kaposi’s sarcoma-associated herpesvirus ORF57 binds to PCBP1 as a functional partner for posttranscriptional regulation and is involved in the regulation of the expression of both cellular and viral genes through IRESs. (PMID:15246275)
• hnRNPE1 is a positive effector of collagen synthesis acting at the post-transcriptional level by interaction with the 3’-untranslated regions (3’-UTRs) of COL1A1, 1A2 mRNAs. (PMID:15514164)
• PCBPs act as a transcription factor and positively regulate mu opioid receptor gene expression in NMB cells (PMID:15933215)
• Thus, we did not find evidence for uniquely interacting partner proteins using this approach, but did identify four new lamin A/C interactive partners (PMID:16248985)
• These results are consistent with a model where hnRNP E1 recruited to A2RE RNA granules by binding to hnRNP A2 inhibits translation of A2RE RNA during granule transport. (PMID:16775011)
• To define the mechanism of STAT3C suppression of transcript. and/or translational activity of NF-kappaB we found that a alphaCP-1 interacted with STAT3C. alphaCP-1 is a K-homol. domain-containing RNA-binding prot with specific for C-rich pyrimidine tracts (PMID:17383969)
• Signal-dependent and coordinated regulation of transcription, splicing, and translation resides in a single coregulator, PCBP1. (PMID:17389360)
• Specific binding of heterogenous nuclear ribonucleoprotein E1 (hnRNP E1) and U1 small nuclear ribonucleoprotein (snRNP) in the pre-spliceosomal complex was associated with silencing of pseudoexon splicing. (PMID:17622584)
• PCBP1 can function as a cytosolic iron chaperone in the delivery of iron to ferritin (PMID:18511687)
• The detailed transcripts and translatants targeted by PCBP1 at a global level. (PMID:18656558)
• reveal a pivotal role for alphaCP1 and alphaCP2 in a p53-independent pathway of p21(WAF) control and cell cycle progression (PMID:19211566)
• We characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells (PMID:20361869)
• PCBP1 plays a major role in the dynamic expression of AR in both male and female androgen-responsive cells. (PMID:20519371)
• Loss of PRL-3 is associated with cancer. (PMID:20609352)
• Overall, the results presented here suggest that cellular PCBP2 and PCBP1 antagonize vesiculovirus growth by affecting viral gene expression and highlight the importance of these two cellular proteins in restricting virus infections. (PMID:21752917)
• hnRNP-E1 as a physiologically relevant, sensitive, cellular sensor of folate deficiency. (PMID:21930702)
• Study on the PCBP1 KH domain recognition of C-rich nucleotides. X-ray diffraction data of PCBP1 were collected to 1.77 Angstrom resolution and the diffraction was consistent with space group P2(1), with unit-cell parameters a = 38.59, b = 111.88, c = 43.42 A, alpha = gamma = 90.0, beta = 93.37 degrees. The unit-cell volume is consistent with the presence of four protein-DNA complexes in the asymmetric unit. (PMID:22102042)
• Our findings unravel a critical role of PCBP1 in regulating MAVS for both fine-tuning the antiviral immunity and preventing inflammation (PMID:22105485)
• Poly(rC)-binding protein 1 indirectly regulated MAP2K2, FOS, FST, TP53 and WNT7B through H2AFX. (PMID:22622828)
• In HCC patients, the expression of THAP11 mRNA significantly correlated with PCBP1 mRNA expression. Our results suggest a novel role of THAP11 in CD44 alternative splicing and hepatoma invasion (PMID:22673507)
• Down-regulation of poly(rC)-binding protein 1 correlates with the malignant transformation of hydatidiform moles. (PMID:22801034)
• High hnRNP-E1 expression is associated with uraemic patients on hemodialysis. (PMID:23439585)
• Stabilization of human eNOS mRNA by hnRNP E1-containing RNP complexes serves as a key protective mechanism against the posttranscriptional inhibitory effects of antisense RNA and microRNA. (PMID:23478261)
• a role for PCBP1 in posttranscriptional control pathways that can alter the coding potential and/or levels of expression of subsets of mRNAs in thetranscriptome. (PMID:23629627)
• PCBP1 and -2 form a complex for iron delivery to ferritin, and all PCBPs may share iron chaperone activity. (PMID:23640898)
• PCBP1 regulates p63 expression via mRNA stability. (PMID:23940783)
• PCBP1 is a positive regulator involved in regulation of EV71 replication in the host specialized membrane-associated replication complex. (PMID:24489926)
• SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1 (PMID:24819169)
• PCBP1 and PCBP2 may serve as iron chaperones to multiple classes of cytosolic nonheme iron enzymes and may have a particular role in restoring metal cofactors that are spontaneously lost in iron deficient cells. (PMID:24843120)
• reduced expression of hnRNP-E1 might be involved with the cervical cancer pathogenesis, with folate playing a role in the natural history of HPV infection (PMID:24848140)
• PCBP1 is a central player in the molecular mechanism causing EMT in GBC-SD cells after TGF-beta treatment; PCBP1 might serve as a useful biomarker for predicting prognosis of gall bladder cancer metastasis (PMID:24889597)
• A novel mechanism by which POLH expression is controlled by PCBP1 via mRNA stability. (PMID:25268038)
• hnRNP E1 is a new regulator of protein disulphide isomerase translation in oxLDL-activated vascular endothelial cells. (PMID:25389050)
• Findings provide mechanistic evidence for HOTAIR overexpression and PCBP1 downregulation in gastric cancer metastasis and their correlation with poor survival. (PMID:25612617)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pcbp1	ENSMUSG00000051695
rattus_norvegicus	Pcbp1	ENSRNOG00000017708
drosophila_melanogaster	Psi	FBGN0014870
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
caenorhabditis_elegans		WBGENE00007534
caenorhabditis_elegans		WBGENE00010908
caenorhabditis_elegans		WBGENE00013347
caenorhabditis_elegans		WBGENE00016489
caenorhabditis_elegans	fubl-4	WBGENE00019692

Paralogs (12): IGF2BP2 (ENSG00000073792), KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), NOVA1 (ENSG00000139910), IGF2BP1 (ENSG00000159217), FUBP1 (ENSG00000162613), HNRNPK (ENSG00000165119), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

Poly(rC)-binding protein 1 — Q15365 (reviewed: Q15365)

Alternative names: Alpha-CP1, Heterogeneous nuclear ribonucleoprotein E1, Nucleic acid-binding protein SUB2.3

All UniProt accessions (2): Q15365, Q53SS8

UniProt curated annotations — full annotation on UniProt →

Function. Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing. (Microbial infection) In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Abundantly expressed in skeletal muscle, thymus and peripheral blood leukocytes while a lower expression is observed in prostate, spleen, testis, ovary, small intestine, heart, liver, adrenal and thyroid glands.

Post-translational modifications. Phosphorylated; lowers poly(rC)-binding activity.

RefSeq proteins (1): NP_006187* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013

UniProt features (30 total): helix 9, modified residue 7, strand 6, domain 3, sequence conflict 2, chain 1, cross-link 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3VKE	X-RAY DIFFRACTION	1.77
1WVN	X-RAY DIFFRACTION	2.1
1ZTG	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15365-F1	69.40	0.13

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): 273, 115, 1, 173, 189, 190, 246, 264

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
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: 240 (showing top): GCM_MSN, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, HNF1_Q6, ATGTTAA_MIR302C, IRF7_01, GCM_PSME1, YGACNNYACAR_UNKNOWN, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, RAHMAN_TP53_TARGETS_PHOSPHORYLATED, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, TGACATY_UNKNOWN, REACTOME_MRNA_SPLICING

GO Biological Process (2): viral RNA genome replication (GO:0039694), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), mRNA binding (GO:0003729), cadherin binding (GO:0045296), sequence-specific single stranded DNA binding (GO:0098847), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), postsynaptic density (GO:0014069), membrane (GO:0016020), nuclear speck (GO:0016607), cytoplasmic ribonucleoprotein granule (GO:0036464), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
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
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	2
nucleic acid binding	2
binding	2
cytoplasm	2
viral genome replication	1
RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
DNA binding	1
RNA binding	1
cell adhesion molecule binding	1
single-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
asymmetric synapse	1
postsynaptic specialization	1
nuclear ribonucleoprotein granule	1
ribonucleoprotein granule	1
extracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

3172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCBP1	EEF1A1	P04719	959
PCBP1	SMAD3	P84022	928
PCBP1	PCBP2	Q15366	919
PCBP1	HNRNPK	P61978	912
PCBP1	HNRNPC	P07910	847
PCBP1	KCNG1	Q9UIX4	820
PCBP1	HNRNPA1	P09651	812
PCBP1	HNRNPA2B1	P22626	780
PCBP1	HNRNPDL	O14979	769
PCBP1	FOLR1	P15328	759
PCBP1	PTBP1	P26599	758
PCBP1	FOLR2	P14207	747
PCBP1	HNRNPA3	P51991	691
PCBP1	SRSF2	Q01130	677
PCBP1	HNRNPL	P14866	675

IntAct

340 interactions, top by confidence:

A	B	Type	Score
SNRPA	PCBP1	psi-mi:“MI:0915”(physical association)	0.780
PCBP1	SNRPA	psi-mi:“MI:0915”(physical association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PAK1	PCBP1	psi-mi:“MI:0915”(physical association)	0.600
PCBP1	PAK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
PAK1	PCBP1	psi-mi:“MI:0407”(direct interaction)	0.600
PCBP1	RBPMS2	psi-mi:“MI:0915”(physical association)	0.600
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
PCBP1	RBM39	psi-mi:“MI:0915”(physical association)	0.560
	PCBP1	psi-mi:“MI:0915”(physical association)	0.560
TLE5	PCBP1	psi-mi:“MI:0915”(physical association)	0.560
IGF2BP3	PCBP1	psi-mi:“MI:0915”(physical association)	0.560
KLF1	PCBP1	psi-mi:“MI:0915”(physical association)	0.560
RBFOX2	PCBP1	psi-mi:“MI:0915”(physical association)	0.560
RBM3	PCBP1	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
SETMAR	HSPA8	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530

BioGRID (869): PCBP1 (Affinity Capture-MS), SNRPA (Two-hybrid), PCBP1 (Affinity Capture-MS), PCBP1 (Affinity Capture-MS), PCBP1 (Affinity Capture-MS), PCBP1 (Affinity Capture-MS), PCBP1 (Affinity Capture-MS), PCBP1 (Affinity Capture-MS), PCBP1 (Affinity Capture-Western), PCBP1 (Reconstituted Complex), PCBP1 (Affinity Capture-Western), PCBP1 (Affinity Capture-Western), PCBP1 (Affinity Capture-Western), PIK3CB (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6G705, A1L3K1, B5DFF2, B5DFI8, G3MWR8, O19048, O19137, O88508, P06730, P29338, P57721, P57722, P60335, Q12800, Q13888, Q15365, Q15366, Q16763, Q1LZ53, Q1RML1, Q28D01, Q2TBV5, Q4W5Z4, Q5E9A3, Q5FVR7, Q5NVP9, Q5TDH0, Q61990, Q6AYU1, Q6DH13, Q6P1K8, Q6ZRY4, Q7RTP6, Q8C6G8, Q8CCI5, Q8CJ19, Q8IY57, Q8N488, Q8VC52, Q921J4

Diamond homologs: A0A0B4KGY6, A0A1W2P872, O19048, O19049, O73932, O74919, P51513, P57721, P57722, P60335, P61978, P61979, P61980, Q15365, Q15366, Q2PFW9, Q32PX7, Q3T0D0, Q4R4M6, Q5E9A3, Q5R5H8, Q5RB68, Q5SF07, Q5ZIQ3, Q5ZLP8, Q61990, Q80WA4, Q8UVD9, Q91WJ8, Q96AE4, Q96I24, Q9JKN6, Q9LZ82, Q9SZH4, Q9UNW9, Q9Y6M1, O00425, P38151, P57723, P57724

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AKT2	“down-regulates activity”	PCBP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA stabilization	5	14.5×	5e-03
positive regulation of translation	6	10.8×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — BL, COAD, COADREAD, MLYM, PRCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
208707	NM_006196.4(PCBP1):c.550C>T (p.Gln184Ter)	Likely pathogenic

SpliceAI

42 predictions. Top by Δscore:

Variant	Effect	Δscore
2:70087813:G:GT	donor_gain	0.3700
2:70088447:T:TA	acceptor_gain	0.3700
2:70088420:G:GT	donor_gain	0.3200
2:70088909:G:GG	donor_gain	0.3200
2:70088052:G:GA	donor_gain	0.2900
2:70088051:T:TA	donor_gain	0.2800
2:70088906:TTT:T	donor_gain	0.2800
2:70088908:T:TG	donor_gain	0.2800
2:70088270:G:GT	donor_gain	0.2700
2:70087984:G:GT	donor_gain	0.2600
2:70088883:C:A	donor_gain	0.2600
2:70088272:A:T	donor_gain	0.2500
2:70088466:G:GC	donor_gain	0.2500
2:70087805:AC:A	acceptor_gain	0.2400
2:70087813:G:T	donor_gain	0.2400
2:70088011:A:AG	donor_gain	0.2400
2:70088012:G:GG	donor_gain	0.2400
2:70088537:CAGAG:C	donor_loss	0.2400
2:70088538:AGAG:A	donor_loss	0.2400
2:70088539:GAGGT:G	donor_loss	0.2400
2:70088540:AG:A	donor_loss	0.2400
2:70088541:GGTG:G	donor_loss	0.2400
2:70088542:GT:G	donor_loss	0.2400
2:70088543:T:G	donor_loss	0.2400
2:70088905:ATT:A	donor_gain	0.2400
2:70088465:T:TG	donor_gain	0.2300
2:70088467:G:GG	donor_gain	0.2300
2:70088468:C:G	donor_gain	0.2300
2:70088558:C:T	donor_loss	0.2300
2:70087806:C:CA	acceptor_gain	0.2200

AlphaMissense

2336 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:70087820:G:A	G26E	1.000
2:70087832:G:A	G30E	1.000
2:70087832:G:T	G30V	1.000
2:70087914:A:C	R57S	1.000
2:70087914:A:T	R57S	1.000
2:70087930:G:C	G63R	1.000
2:70087931:G:A	G63D	1.000
2:70088084:G:A	G114E	1.000
2:70088135:T:A	V131D	1.000
2:70087796:T:C	L18P	0.999
2:70087819:G:A	G26R	0.999
2:70087819:G:C	G26R	0.999
2:70087826:T:A	I28N	0.999
2:70087829:T:A	I29N	0.999
2:70087831:G:A	G30R	0.999
2:70087831:G:C	G30R	0.999
2:70087831:G:T	G30W	0.999
2:70087840:G:A	G33R	0.999
2:70087840:G:C	G33R	0.999
2:70087841:G:A	G33E	0.999
2:70087841:G:T	G33V	0.999
2:70087850:T:A	V36D	0.999
2:70087861:C:A	R40S	0.999
2:70087862:G:C	R40P	0.999
2:70087889:T:A	I49N	0.999
2:70087889:T:G	I49S	0.999
2:70087913:G:C	R57T	0.999
2:70087913:G:T	R57I	0.999
2:70087931:G:T	G63V	0.999
2:70087955:C:A	A71D	0.999

dbSNP variants (sampled 300 via entrez): RS1000225671 (2:70086135 C>A), RS1001541706 (2:70087062 G>T), RS1001644000 (2:70087510 C>T), RS1001991713 (2:70087371 G>A), RS1002236496 (2:70086798 G>A,C), RS1002267819 (2:70086926 G>A,C), RS1002382400 (2:70086989 G>A,C), RS1003236654 (2:70086161 C>T), RS1004334900 (2:70086417 G>A), RS1004881538 (2:70087353 GGGTT>G), RS1005207049 (2:70086937 C>T), RS1006270408 (2:70085633 A>G), RS1006814736 (2:70087015 G>A,C), RS1007136041 (2:70087232 G>A,T), RS1008117012 (2:70086568 C>G)

Disease associations

OMIM: gene MIM:601209 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002481_1	Acne (severe)	5.000000e-06
GCST006661_199	Male-pattern baldness	3.000000e-08
GCST90000025_752	Appendicular lean mass	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295825 (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
7.28	Kd	52.95	nM	CHEMBL5653589
7.28	ED50	52.95	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 13 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	2148942: Binding affinity to human PCBP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0529	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression, affects expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tobacco Smoke Pollution	affects expression, increases methylation	2
Valproic Acid	decreases expression, affects expression	2
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases reaction, decreases activity, affects binding	1
butyraldehyde	decreases expression	1
coumarin	affects phosphorylation	1
cupric oxide	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	affects expression	1
gambierol	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
tetraarsenic tetrasulfide	affects expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Vorinostat	decreases expression	1
Aspirin	decreases expression	1
Benztropine	affects cotreatment, decreases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118766	Binding	Binding affinity to PCBP1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice