PCBP2

Summary

PCBP2 (poly(rC) binding protein 2, HGNC:8648) is a protein-coding gene on chromosome 12q13.13, encoding Poly(rC)-binding protein 2 (Q15366). Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. It is a common-essential gene (DepMap: required in 99.2% of cancer cell lines).

The protein encoded by this gene appears to be multifunctional. Along with PCBP-1 and hnRNPK, it is one of the major cellular poly(rC)-binding proteins. The encoded protein contains three K-homologous (KH) domains which may be involved in RNA binding. Together with PCBP-1, this protein also functions as a translational coactivator of poliovirus RNA via a sequence-specific interaction with stem-loop IV of the IRES, promoting 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. This multiexon structural mRNA is thought to be retrotransposed to generate PCBP-1, an intronless gene with functions similar to that of PCBP2. This gene and PCBP-1 have paralogous genes (PCBP3 and PCBP4) which are thought to have arisen as a result of duplication events of entire genes. This gene also has two processed pseudogenes (PCBP2P1 and PCBP2P2). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5094 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 55 total
• Regional missense constraint (gnomAD): 3 of 7 regions constrained (≈70% of expected missense variation)
• GTEx eGene: eQTL in 11 tissues, sQTL in 11 (q < 0.05)
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.14 (highly constrained)
• MANE Select transcript: NM_031989
• Interaction hub: 2,801 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8648
Approved symbol	PCBP2
Name	poly(rC) binding protein 2
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	HNRPE2, hnRNP-E2, HNRNPE2
Ensembl gene	ENSG00000197111
Ensembl biotype	protein_coding
OMIM	601210
Entrez	5094

Gene structure

Transcript identifiers

Ensembl transcripts: 127 — 99 protein_coding, 22 nonsense_mediated_decay, 6 retained_intron

MANE Select: ENST00000546463

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 6, TSL 2: 5, TSL 3: 5, TSL 4: 1, TSL 5: 9

ENST00000546463, ENST00000359282, ENST00000359462, ENST00000437231, ENST00000439930, ENST00000447282, ENST00000455667, ENST00000546652, ENST00000547048, ENST00000547859, ENST00000547987, ENST00000548190, ENST00000548933, ENST00000549272, ENST00000549863, ENST00000550192, ENST00000550520, ENST00000550585, ENST00000550733, ENST00000550910, ENST00000551104, ENST00000552296, ENST00000552819, ENST00000552980, ENST00000553064, ENST00000562264, ENST00000868134, ENST00000868135, ENST00000868136, ENST00000868137, ENST00000868138, ENST00000868139, ENST00000868140, ENST00000868141, ENST00000868142, ENST00000868143, ENST00000868144, ENST00000868145, ENST00000868146, ENST00000868147, ENST00000868148, ENST00000868149, ENST00000868150, ENST00000868151, ENST00000868152, ENST00000868153, ENST00000868154, ENST00000868155, ENST00000868156, ENST00000868157, ENST00000868158, ENST00000868159, ENST00000868160, ENST00000868161, ENST00000868162, ENST00000868163, ENST00000868164, ENST00000868165, ENST00000868166, ENST00000923986, ENST00000923987, ENST00000923988, ENST00000946734, ENST00000946735, ENST00000946736, ENST00000946737, ENST00000974711, ENST00000974712, ENST00000974713, ENST00000974714, ENST00000974715, ENST00000974716, ENST00000974717, ENST00000974718, ENST00000974719, ENST00000974720, ENST00000974721, ENST00000974722, ENST00000974723, ENST00000974724, ENST00000974725, ENST00000974726, ENST00000974727, ENST00000974728, ENST00000974729, ENST00000974731, ENST00000974732, ENST00000974734, ENST00000974735, ENST00000974736, ENST00000974737, ENST00000974738, ENST00000974739, ENST00000974740, ENST00000974741, ENST00000974742, ENST00000974745, ENST00000974747, ENST00000974749, ENST00000974750, ENST00000974751, ENST00000974752, ENST00000974753, ENST00000974754, ENST00001044292, ENST00001044293, ENST00001044294, ENST00001044295, ENST00001044296, ENST00001044297, ENST00001044298, ENST00001044299, ENST00001044300, ENST00001044301, ENST00001044302, ENST00001044303, ENST00001044304, ENST00001063636, ENST00001063637, ENST00001063638, ENST00001098000, ENST00001098001, ENST00001098002, ENST00001108527, ENST00001108528, ENST00001117058, ENST00001142022

RefSeq mRNA: 7 — MANE Select: NM_031989 NM_001098620, NM_001128911, NM_001128912, NM_001128913, NM_001128914, NM_005016, NM_031989

CCDS: CCDS44900, CCDS44901, CCDS44902, CCDS44903, CCDS44904, CCDS55830, CCDS8859

Canonical transcript exons

ENST00000546463 — 15 exons

Exon	Start	End
ENSE00003480577	53455347	53455370
ENSE00003489517	53455461	53455493
ENSE00003493178	53471638	53471807
ENSE00003523658	53465932	53465973
ENSE00003532538	53454726	53454869
ENSE00003577141	53467221	53467293
ENSE00003602867	53455885	53456001
ENSE00003627413	53464760	53464852
ENSE00003645717	53462493	53462567
ENSE00003673222	53459272	53459403
ENSE00003677361	53467805	53467843
ENSE00003691939	53468777	53468832
ENSE00003787788	53461015	53461143
ENSE00003899734	53452102	53452376
ENSE00003902597	53479406	53481162

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 856.4611 / max 31777.5021, expressed in 1828 samples.

Highest expression (Bgee): ganglionic eminence, ventricular zone, stromal cell of endometrium, testis, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PCBP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	sqtl	1.6e-13	+0.49	12:53446172:C:G
Esophagus Gastroesophageal Junction	sqtl	2.2e-06	-0.46	12:53446172:C:G
Spleen	sqtl	8.8e-04	+0.45	12:53461970:A:G
Colon Sigmoid	sqtl	1.5e-03	+0.28	12:53446172:C:G
Skin Sun Exposed Lower leg	sqtl	2.0e-03	-0.25	12:53446172:C:G
Esophagus Muscularis	sqtl	2.8e-03	+0.27	12:53446172:C:G
Thyroid	eqtl	3.6e-03	-0.10	12:53446172:C:G
Artery Tibial	sqtl	5.9e-03	-0.76	12:53423793:G:T
Heart Atrial Appendage	sqtl	7.6e-03	-0.37	12:53446172:C:G
Nerve Tibial	eqtl	9.9e-03	-0.35	12:54151095:A:C
Artery Aorta	eqtl	1.0e-02	+0.20	12:53479582:C:T
Muscle Skeletal	sqtl	1.3e-02	-1.38	12:53326710:G:A
Cells Cultured fibroblasts	eqtl	2.6e-02	-0.32	12:53550184:G:A
Spleen	eqtl	3.0e-02	+0.14	12:54397712:C:T
Brain Hypothalamus	eqtl	3.2e-02	-0.19	12:54116172:C:T
Brain Nucleus accumbens basal ganglia	eqtl	3.4e-02	+0.14	12:53752667:G:A
Lung	eqtl	3.4e-02	-0.19	12:53895357:G:A
Uterus	eqtl	3.5e-02	-0.94	12:52833554:G:A
Esophagus Gastroesophageal Junction	eqtl	3.8e-02	+0.17	12:53668236:G:A
Brain Spinal cord cervical c-1	sqtl	4.2e-02	+0.57	12:53287171:C:T

FANTOM5 promoters

showing 10 of 15 alternative TSS:

Promoter ID	TPM avg	Samples expressed
125766	843.2439	1828
125780	3.8747	1409
125772	2.4753	1215
125776	1.6751	995
125774	1.3197	715
125773	1.1389	591
125778	1.0963	619
125779	0.6091	310
125784	0.5348	299
125771	0.3186	136

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.69	gold quality
ventricular zone	UBERON:0003053	99.64	gold quality
stromal cell of endometrium	CL:0002255	99.62	gold quality
left testis	UBERON:0004533	99.61	gold quality
cortical plate	UBERON:0005343	99.61	gold quality
right testis	UBERON:0004534	99.60	gold quality
left ovary	UBERON:0002119	99.57	gold quality
right adrenal gland cortex	UBERON:0035827	99.57	gold quality
right lobe of thyroid gland	UBERON:0001119	99.56	gold quality
left lobe of thyroid gland	UBERON:0001120	99.56	gold quality
right adrenal gland	UBERON:0001233	99.55	gold quality
right ovary	UBERON:0002118	99.55	gold quality
metanephros cortex	UBERON:0010533	99.55	gold quality
endocervix	UBERON:0000458	99.54	gold quality
left adrenal gland	UBERON:0001234	99.54	gold quality
right lung	UBERON:0002167	99.54	gold quality
body of pancreas	UBERON:0001150	99.53	gold quality
colonic epithelium	UBERON:0000397	99.52	gold quality
embryo	UBERON:0000922	99.52	gold quality
right uterine tube	UBERON:0001302	99.52	gold quality
skin of leg	UBERON:0001511	99.52	gold quality
left adrenal gland cortex	UBERON:0035825	99.52	gold quality
tibial nerve	UBERON:0001323	99.51	gold quality
body of uterus	UBERON:0009853	99.51	gold quality
body of stomach	UBERON:0001161	99.50	gold quality
skin of abdomen	UBERON:0001416	99.50	gold quality
cerebellar hemisphere	UBERON:0002245	99.50	gold quality
mucosa of stomach	UBERON:0001199	99.49	gold quality
thyroid gland	UBERON:0002046	99.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.48	gold quality
upper lobe of left lung	UBERON:0008952	99.46	gold quality
gall bladder	UBERON:0002110	99.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.44	gold quality
upper lobe of lung	UBERON:0008948	99.43	gold quality
granulocyte	CL:0000094	99.42	gold quality
ectocervix	UBERON:0012249	99.42	gold quality
adrenal cortex	UBERON:0001235	99.41	gold quality
popliteal artery	UBERON:0002250	99.41	gold quality
adrenal gland	UBERON:0002369	99.41	gold quality
tibial artery	UBERON:0007610	99.41	gold quality
omental fat pad	UBERON:0010414	99.41	gold quality
left uterine tube	UBERON:0001303	99.40	gold quality
right coronary artery	UBERON:0001625	99.40	gold quality
minor salivary gland	UBERON:0001830	99.40	gold quality
peritoneum	UBERON:0002358	99.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.40	gold quality
stomach	UBERON:0000945	99.39	gold quality
cerebellar cortex	UBERON:0002129	99.39	gold quality
descending thoracic aorta	UBERON:0002345	99.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.39	gold quality
leukocyte	CL:0000738	99.38	gold quality
monocyte	CL:0000576	99.37	gold quality
aorta	UBERON:0000947	99.37	gold quality
mononuclear cell	CL:0000842	99.36	gold quality
lymph node	UBERON:0000029	99.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.36	gold quality
left coronary artery	UBERON:0001626	99.35	gold quality
adenohypophysis	UBERON:0002196	99.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.35	gold quality
transverse colon	UBERON:0001157	99.34	gold quality
lower esophagus	UBERON:0013473	99.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.34	gold quality
thoracic aorta	UBERON:0001515	99.32	gold quality
rectum	UBERON:0001052	99.31	gold quality
ascending aorta	UBERON:0001496	99.31	gold quality
small intestine	UBERON:0002108	99.31	gold quality
zone of skin	UBERON:0000014	99.30	gold quality
saliva-secreting gland	UBERON:0001044	99.27	gold quality
smooth muscle tissue	UBERON:0001135	99.27	gold quality
spleen	UBERON:0002106	99.27	gold quality
esophagus	UBERON:0001043	99.23	gold quality
coronary artery	UBERON:0001621	99.22	gold quality
cerebellum	UBERON:0002037	99.20	gold quality
right atrium auricular region	UBERON:0006631	99.20	gold quality
pituitary gland	UBERON:0000007	99.19	gold quality
caput epididymis	UBERON:0004358	99.19	gold quality
colon	UBERON:0001155	99.17	gold quality
sigmoid colon	UBERON:0001159	99.17	gold quality
islet of Langerhans	UBERON:0000006	99.16	gold quality
vermiform appendix	UBERON:0001154	99.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.16	gold quality
bone marrow cell	CL:0002092	99.15	gold quality
intestine	UBERON:0000160	99.15	gold quality
esophagus mucosa	UBERON:0002469	99.14	gold quality
blood	UBERON:0000178	99.13	gold quality
fundus of stomach	UBERON:0001160	99.13	gold quality
mucosa of transverse colon	UBERON:0004991	99.13	gold quality
corpus epididymis	UBERON:0004359	99.11	gold quality
caecum	UBERON:0001153	99.10	gold quality
large intestine	UBERON:0000059	99.09	gold quality
skin of hip	UBERON:0001554	99.09	gold quality
cartilage tissue	UBERON:0002418	99.09	gold quality
right frontal lobe	UBERON:0002810	99.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.08	gold quality
upper leg skin	UBERON:0004262	99.06	gold quality
superficial temporal artery	UBERON:0001614	99.05	gold quality
right lobe of liver	UBERON:0001114	99.04	gold quality
mouth mucosa	UBERON:0003729	99.04	gold quality
adult mammalian kidney	UBERON:0000082	99.03	gold quality
trabecular bone tissue	UBERON:0002483	99.03	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	915.40
E-MTAB-10042	yes	10.80
E-CURD-122	yes	5.51
E-CURD-79	no	1228.27
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	814.6	medium
Retina	tissue	616.6
Thymus	tissue	506.4
Ovary	tissue	499.8	low
Kidney	tissue	499.1	high
Liver	tissue	475.8	high
Skeletal muscle	tissue	450.8	medium
Tonsil	tissue	426.8	medium
Pancreas	tissue	412.3	medium
Parathyroid gland	tissue	410.9	medium
Choroid plexus	tissue	389.6
Thyroid gland	tissue	388.4	medium
Fallopian tube	tissue	383.6	medium
Tongue	tissue	374.9
Lymph node	tissue	355.7	medium
Spinal cord	tissue	354.1
Epididymis	tissue	345.8	medium
Testis	tissue	339.7	high
Cervix	tissue	338.1	medium
Adipose tissue	tissue	332.8	not detected
Locus coeruleus	tissue	330.9
Caudate putamen	tissue	329.9
Cerebellum	tissue	328.9	high
Adrenal gland	tissue	328.4	medium
Nucleus accumbens	tissue	326.8
Superior colliculi	tissue	323.7
Breast	tissue	322.4	medium
Skin 1	tissue	321.9	medium
Heart muscle	tissue	318.7	medium
Duodenum	tissue	315.0	medium
Thalamus	tissue	314.9
Pons	tissue	313.0
Smooth muscle	tissue	311.9	low
Endometrium 1	tissue	311.4	medium
Medulla oblongata	tissue	308.0
Frontal cortex	tissue	307.4
Rectum	tissue	305.6	medium
Small intestine	tissue	305.6	medium
Midbrain	tissue	305.5
Spleen	tissue	305.1	medium
Salivary gland	tissue	303.4	medium
Postcentral gyrus	tissue	302.8
Vagina	tissue	299.2	medium
Hippocampus	tissue	288.3	low
Gallbladder	tissue	282.6	medium
Placenta	tissue	281.5	medium
Stomach 1	tissue	280.7	high
Substantia nigra	tissue	275.7
Hypothalamus	tissue	275.4
Periaqueductal gray	tissue	275.1
Urinary bladder	tissue	273.3	medium
Colon	tissue	272.7	medium
Lung	tissue	269.3	medium
Corpus callosum	tissue	266.7
Esophagus	tissue	263.1	medium
Seminal vesicle	tissue	249.2	medium
Appendix	tissue	248.1	medium
Septum	tissue	235.3
Putamen	tissue	232.0
Hippocampal formation	tissue	226.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (428.8), Corpus callosum, genu (white matter) (424.7), Flocculonodular lobe (416.5), Blood vessel (411.4), Corpus callosum, splenium (white matter) (396.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNRNPK

miRNA regulators (miRDB)

Targeting PCBP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 133 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6721-5P	99.93	68.92	2981

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.139, missense Z 4.66 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000546463 splits into 7 regions with different missense tolerance; 3 are missense-constrained (≈70% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:53,454,801–53,454,843	11 / 16.4	0.67	no
12:53,454,844–53,455,954	7 / 67.4	0.10	yes (p 1.9e-13)
12:53,455,955–53,459,312	24 / 37.1	0.65	no
12:53,459,313–53,461,091	13 / 71.8	0.18	yes (p 3.9e-12)
12:53,461,092–53,462,532	20 / 43.1	0.46	no
12:53,462,533–53,464,818	35 / 45.5	0.77	no
12:53,464,819–53,479,439	51 / 193.0	0.26	yes (p 1.6e-24)
DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): EFO-21 (-3.548), COLO-678 (-2.573), Daoy (-2.557), ZR-75-1 (-2.454), SK-RC-52 (-2.454), PANC-1 (-2.315), SU-DHL-10 (-2.278), HEL 92.1.7 (-2.223), KMRC-20 (-2.216), C8166 (-2.188), SUP-M2 (-2.18), JHOM-1 (-2.172), SCC-25 (-2.163), COR-L279 (-2.162), KU812 (-2.142).

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)
• specific PCBP2 domains may have distinct roles for differential picornavirus template utilization during viral translation and RNA replication (PMID:12414943)
• 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)
• Data suggest that poly(C)-binding protein 2 KH domain 1 interactions with telomeric DNA and telomerase RNA may be involved in the regulation of telomere/telomerase functions. (PMID:15331611)
• PCBP2 KH1 binds to C-rich strand of human telomeric DNA, indicating that that PCBPs may participate in mechanisms involved in the regulation of telomere/telomerase functions (PMID:16186123)
• 2’,5’-oligoadenylate synthetase activation may occur in prostate cancer cells stimulated by cellular mRNAs for PCBP2. (PMID:17145707)
• Downregulation of HnRNP E2 is associated with oral cancer (PMID:17219427)
• molecular model of the interaction of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA. (PMID:17426136)
• Crystal structures of PCBP2 KH1 domain in complex with a 12-nucleotide DNA corresponding to two repeats of the human C-rich strand telomeric DNA and its RNA equivalent. (PMID:17526645)
• Study shows that through the loss of the KH3 domain, and therefore loss of its ability to function in translation, PCBP2 can mediate the switch from viral translation to RNA replication. (PMID:17581994)
• validated occurrence of an unusual TG 3’ splice site in intron 7 (PMID:17672918)
• The interaction of PCBP2 with RNA target sequences at the 5’ end of the coxsackievirus B3 genome was investigated. (PMID:18086560)
• PCBP2 may be involved in stress-induced remodeling of mRNP complexes and that it may also play a role in the rapid transition of certain silenced mRNAs into a translationally active state. (PMID:18174314)
• Using a novel protein-RNA tethering system, We establish PCBP2 as an essential co-factor in the initiation of poliovirus negative-strand synthesis. (PMID:18252259)
• The authors showed that the PCBP2 linker domain modulates binding to poliovirus stem-loop IV RNA via a mechanism that is not inhibited by the antibody. (PMID:18656221)
• SIN1 and PCBP2 are generally coregulated with large numbers of genes implicated in both cell survival and death and in cellular stress responses, including RNA translation and processing (PMID:18687895)
• analysis of the human poly(C)-binding protein containing the first and second KH domains reveals insights into its regulatory mechanisms (PMID:18701464)
• The data demonstrate interaction of isolated PCBP2 KH1 and KH3 domains to four distinct target sites within the 5’-nontranslated region of the CVB3 genomic RNA. (PMID:18929541)
• reveal a pivotal role for alphaCP1 and alphaCP2 in a p53-independent pathway of p21(WAF) control and cell cycle progression (PMID:19211566)
• Results establish the compositional diversity among P-bodies, and that PCBP2, probably in complex with other mRNP factors, may dynamically recognize such differences and accumulate to specific P-bodies. (PMID:19230839)
• PCBP2-AIP4 axis defines a new signaling cascade for MAVS degradation and ‘fine tuning’ of antiviral innate immunity. (PMID:19881509)
• The authors established that the 5’CL-PCBP complex is required for optimal poliovirus viral RNA translation and identified the KH3 domain of PCBP2 as the functional region. (PMID:19945132)
• Study reports that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. (PMID:20211135)
• study demonstrates the mechanism of the participation of PCBP2 in hepatitis C virus translation and replication (PMID:21632751)
• SRp75 inhibits splicing of tau exon 10 by binding to the CA repeat in the intronic splicing silencer downstream of the exon, and requires hnRNPG to exert its full regulatory effect on tau exon 10. (PMID:21723381)
• 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)
• PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3’Untranslated Region (UTR) of these two molecules. (PMID:22022391)
• PCBP2 specifically and selectively interacts with rabies virus glycoprotein mRNA and this interaction may contribute to the post-transcriptional regulation of glycoprotein expression (PMID:22438951)
• Cytosolic iron may modulate the association between PCBP2 and Dicer, as well as the multimerization of PCBP2 and its ability to bind to miRNA precursors (PMID:22633452)
• PCBP2 is an RNA-binding protein that modulates glioma growth by regulating FHL3 (PMID:23585479)
• PCBP2 controls the 3’ processing of its own transcript. (PMID:23629627)
• PCBP1 and -2 form a complex for iron delivery to ferritin, and all PCBPs may share iron chaperone activity. (PMID:23640898)
• Inhibition of poliovirus-induced cleavage of cellular PCBP2 protein reduces the viral RNA replication. (PMID:24371074)
• PCBP2 and PTB are differentially cleaved by human rhinovirus proteinase in infected cells. (PMID:24418535)
• SIRT6 inhibits glioma cell proliferation and colony formation in vitro and glioma cell growth in vivo in a PCBP2 dependent manner. SIRT6 inhibits PCBP2 expression through deacetylating H3K9ac and SIRT6 acts as a tumor suppressor in glioma. (PMID:24607900)
• PCBP2-depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. miR-34a is a target of PCBP2, and miR-34a is critically essential for the function of PCBP2. (PMID:24796666)
• 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)
• STAT3 functions via cellular PCBP2 to regulate B-cell lytic susceptibility by restraining Epstein-Barr Virus lytic activation. (PMID:25717101)
• Protein and mRNA levels of PCBP2 were down-regulated under insulin-resistant conditions. Over-expression of PCBP2 inhibits HIF1alpha and STAT3 pathway. (PMID:26002461)
• PCBP2 knockdown promoted angiotensin II-induced hypertrophy (increase in cell size, protein synthesis and activation of fetal genes) of cardiomyocytes, while PCBP2 overexpression obtained oppose effects. (PMID:26116532)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcbp2	ENSDARG00000099039
mus_musculus	Pcbp2	ENSMUSG00000056851
rattus_norvegicus	Pcbp2	ENSRNOG00000036852
rattus_norvegicus	AC128212.1	ENSRNOG00000054355
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
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), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:108202) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	1
hemorrhage	1
postnatal lethality, complete penetrance	1
lethality throughout fetal growth and development, complete penetrance	1
embryonic lethality during organogenesis, incomplete penetrance	1
abnormal erythroblast morphology	1
abnormal platelet cell number	1
subcutaneous edema	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharomyces cerevisiae YJM789	A6ZKR5	100.0%	Diamond
Saccharomyces cerevisiae JAY291	C7GND0	100.0%	Diamond
Saccharomyces cerevisiae EC1118	C8Z3W4	100.0%	Diamond
Oryctolagus cuniculus	O19048	100.0%	Diamond
Saccharomyces cerevisiae S288C	P38199	100.0%	Diamond
Bos taurus	Q5E9A3	100.0%	Diamond
Saccharomyces cerevisiae RM11-1a	B3LNH0	99.7%	Diamond
Macaca fascicularis	Q2PFW9	99.6%	Diamond
Gallus gallus	O42254	94.5%	Diamond
Lachancea thermotolerans CBS 6340	C5DIR2	59.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ATF7-NPFF	protein-coding	114108587
AMHR2	protein-coding	269
PRR13	protein-coding	54458
TARBP2	protein-coding	6895
MAP3K12	protein-coding	7786
NPFF	protein-coding	8620
ATF7-AS1	ncRNA	100652999
PCBP2-OT1	ncRNA	102157401
ATF7	protein-coding	11016
ATF7-AS2	ncRNA	124902937
SP1	protein-coding	6667
SP7	protein-coding	121340

Protein

Protein identifiers

Poly(rC)-binding protein 2 — Q15366 (reviewed: Q15366)

Alternative names: Alpha-CP2, Heterogeneous nuclear ribonucleoprotein E2

All UniProt accessions (12): A0A384N6B9, Q15366, F8VRH0, F8VTZ0, F8VXH9, F8VZX2, F8W0G4, F8W1G6, H3BND9, H3BRU6, H3BSP4, H3BSS4

UniProt curated annotations — full annotation on UniProt →

Function. Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. Major cellular poly(rC)-binding protein. Also binds poly(rU). Acts as a negative regulator of antiviral signaling. Negatively regulates cellular antiviral responses mediated by MAVS signaling. It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation. Negativeley regulates the cGAS-STING pathway via interaction with CGAS, preventing the formation of liquid-like droplets in which CGAS is activated. Together with PCBP1, required for erythropoiesis, possibly by regulating mRNA splicing. (Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation. Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD.

Subunit / interactions. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Interacts with IFIH1 and RNF135. Interacts with MAVS (via C-terminus) and ITCH (via WW domains). Interacts with CGAS; preventing the formation of liquid-like droplets in which CGAS is activated.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Detected in all tissues examined.

Post-translational modifications. Phosphorylated. The non-phosphorylated form(s) exhibited the strongest poly(rC)-binding activity. (Microbial infection) Proteolytically cleaved by picornavirus proteinase 3CD.

Domain organisation. The KH domains mediates poly(C) binding.

Isoforms (8)

UniProt ID	Names	Canonical?
Q15366-1	1	yes
Q15366-2	2
Q15366-3	3
Q15366-4	4
Q15366-5	5
Q15366-6	6
Q15366-7	7
Q15366-8	8

RefSeq proteins (7): NP_001092090, NP_001122383, NP_001122384, NP_001122385, NP_001122386, NP_005007, NP_114366* (*=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 (40 total): helix 13, strand 10, modified residue 5, splice variant 4, domain 3, cross-link 3, chain 1, site 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
2P2R	Crystal structure of the third KH domain of human Poly(C)-Binding Protein-2 in complex …	X-RAY DIFFRACTION	1.6
2AXY	Crystal Structure of KH1 domain of human Poly(C)-binding protein-2 with C-rich strand of …	X-RAY DIFFRACTION	1.7
2PQU	Crystal structure of KH1 domain of human PCBP2 complexed to single-stranded 12-mer …	X-RAY DIFFRACTION	2.12
2PY9	Protein-RNA Interaction involving KH1 domain from Human Poly(C)-Binding Protein-2	X-RAY DIFFRACTION	2.56
2JZX	PCBP2 KH1-KH2 domains	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15366-F1	67.42	0.05

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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 (1)

Position	Role
253–254	cleavage, by viral proteinase 3cd

Post-translational modifications (8)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	115, 185, 322
Phosphoserine	173, 189, 272, 364, 365

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 17; 8 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-9918481	Dengue Virus-Host Interactions ⚕	curated
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses ⚕	curated
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling	curated
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	curated
R-HSA-9770562	mRNA Polyadenylation	curated
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9678108	SARS-CoV-1 Infection ⚕	—
R-HSA-9692914	SARS-CoV-1-host interactions ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72172	mRNA Splicing	—

MSigDB gene sets: 374 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_INNATE_IMMUNE_SYSTEM, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, LFA1_Q6, MORF_UBE2I, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, MEF2_02, CAGCTG_AP4_Q5, BOYLAN_MULTIPLE_MYELOMA_D_DN, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (11): mRNA metabolic process (GO:0016071), viral RNA genome replication (GO:0039694), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), innate immune response (GO:0045087), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of defense response to virus (GO:0050687), defense response to virus (GO:0051607), IRES-dependent viral translational initiation (GO:0075522), chromatin looping (GO:0140588), negative regulation of cGAS/STING signaling pathway (GO:0160049), immune system process (GO:0002376)

GO Molecular Function (10): single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), mRNA binding (GO:0003729), enzyme binding (GO:0019899), ubiquitin protein ligase binding (GO:0031625), lncRNA binding (GO:0106222), promoter-enhancer loop anchoring activity (GO:0140585), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

14 top-level categories:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
SARS-CoV-1-host interactions	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Immune System	1
Innate Immune System	1
Disease	1
Processing of Capped Intron-Containing Pre-mRNA	1
SARS-CoV Infections	1
Viral Infection Pathways	1
SARS-CoV-1 Infection	1
Infectious disease	1

GO top-level categories

38 GO namespaces:

Category	Terms
cellular anatomical structure	4
nucleic acid binding	2
RNA binding	2
binding	2
RNA metabolic process	1
viral genome replication	1
RNA biosynthetic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
immune response	1
defense response to symbiont	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of defense response to virus	1
defense response to virus	1
defense response	1
response to virus	1
viral process	1
viral translation	1
chromatin organization	1
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1
cGAS/STING signaling pathway	1
biological_process	1
DNA binding	1
protein binding	1
ubiquitin-like protein ligase binding	1
chromatin loop anchoring activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
extracellular vesicle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO term	NS	Evidence
IRES-dependent viral translational initiation	BP	direct assay
chromatin looping	BP	mutant phenotype
negative regulation of cGAS/STING signaling pathway	BP	direct assay
negative regulation of defense response to virus	BP	mutant phenotype
proteasome-mediated ubiquitin-dependent protein catabolic process	BP	mutant phenotype
viral RNA genome replication	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
membrane	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	direct assay
enzyme binding	MF	physical interaction
lncRNA binding	MF	direct assay
promoter-enhancer loop anchoring activity	MF	mutant phenotype
ubiquitin protein ligase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,801 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCBP2	KCNG1	Q9UIX4	824
PCBP2	CEBPA	P49715	668
PCBP2	HNRNPA2B1	P22626	614
PCBP2	GEMIN5	Q8TEQ6	610
PCBP2	STEAP3	Q658P3	594
PCBP2	SRSF2	Q01130	582
PCBP2	HNRNPC	P07910	580
PCBP2	ABL1	P00519	560
PCBP2	HNRNPA1	P09651	558
PCBP2	HNRNPDL	O14979	558
PCBP2	MAVS	Q7Z434	554
PCBP2	KCNF1	Q9H3M0	548
PCBP2	PTBP1	P26599	547
PCBP2	DHX30	Q7L2E3	539
PCBP2	FMR1	Q06787	537

IntAct

Human interaction partners of PCBP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
SRSF3	physical association	0.580	3
SNRPA	physical association	0.560	3
PABPC1	direct interaction	0.530	2
PCBP1	physical association	0.510	2
IGF2BP1	colocalization	0.430	1
VCP	physical association	0.400	1
NKAP	physical association	0.370	1
PRPF40A	physical association	0.370	1
SF3B2	physical association	0.370	1
SLU7	physical association	0.370	1
WDR77	physical association	0.370	1
WDR83	physical association	0.370	1
HNRNPL	association	0.350	1
PAPOLA	association	0.350	1
QKI	physical association	0.000	1

BioGRID (450 interactions; top human partners by supporting records): PCBP1 (Affinity Capture-Western; 15 records), PCBP3 (Affinity Capture-MS; 9 records), HNRNPK (Two-hybrid; 8 records), YAP1 (Affinity Capture-MS; 5 records), HNRNPL (Two-hybrid; 4 records), PARK2 (Affinity Capture-MS; 4 records), PTBP1 (Two-hybrid; 4 records), MAVS (Affinity Capture-Western; 3 records), PABPC1 (Co-fractionation; 3 records), PHGDH (Affinity Capture-MS; 3 records), TFCP2 (Affinity Capture-MS; 3 records), TRIB2 (Affinity Capture-MS; 3 records), UBC (Reconstituted Complex; 3 records), CCNF (Affinity Capture-MS; 2 records), CDK9 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 9 of 15 signaling interactions:

A	Effect	B	Mechanism
NLRX1	“up-regulates activity”	PCBP2	binding
PCBP2	“down-regulates quantity by destabilization”	MAVS	binding
PCBP2	“up-regulates activity”	ITCH	binding
MAPK1	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
MAPK3	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
ERK1/2	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
LPAR	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
Ggamma	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
Gbeta	“up-regulates quantity by stabilization”	PCBP2	phosphorylation

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
Spliceosome, E complex	129	RBM17, DDX39A, GEMIN2, NCBP2, PRPF31, SART3, SF3A2, SNRPA, SRSF7, DDX39B, DHX15, GEMIN5, SCAF4, SMARCB1, SNRPD3, SYNCRIP, U2AF2, HNRNPC, SF3B2, SMARCC2, SFSWAP, USP39, GEMIN6, HNRNPK, RBM42, SF3B1, SF3B4, SNRPG, SRSF6, BCAS2, SMN1, CPSF7, SMARCE1, SRSF8, ARID1A, LSM4, SNRPC, CHD8, FUS, SNRNP70, SRSF11, NUDT21, PBRM1, SNRPB2, SNRPD1, YBX1, SF1, SNRPD2, SRSF2, SRSF5, PPIH, SRSF3, DDX20, SART1, SRSF1, SRSF4, PRPF19, RBM39, RBMXL2, SREK1, PRPF3, SMARCA2, U2AF1, SF3B6, SMARCA1, CPSF1, DDX23, DHX9, RUVBL1, SNRPF, SRRM2, ALYREF, HNRNPA0, HNRNPH1, PCBP2, RBM10, SF3B3, STRAP, HNRNPR, RBM25, ACTBL2, CHERP, SNRPA1, ACTL6A, DDX46, HNRNPL, RBM7, CPSF6, ARID2, DNAJC8, EFTUD2, KHSRP, RUVBL2, SMARCA4, PCBP1, SNRNP40, SNRPE, PRPF4, PRPF8, SF3A1, SF3A3, SNRNP200, ZCCHC8, DDX5, LUC7L3, SMARCC1, HNRNPA2B1, HNRNPD, HTATSF1, LUC7L2, PHF5A, PRPF6, SMARCD1, SNRPB, GEMIN8, U2SURP, NCBP1, GEMIN4, HNRNPU, MTREX, ARID1B, CHD4, HNRNPM, PRPF40A, HNRNPF, SRRT, DDX17, HNRNPA1, PUF60
LATS1-PCBP2-SAV1-STK3-STK4 complex	5	LATS1, PCBP2, SAV1, STK3, STK4
ITCH-MAVS-PCBP2 complex	3	ITCH, MAVS, PCBP2
CNBP-PCBP2 complex	2	CNBP, PCBP2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
mRNA Polyadenylation	7	41.0×	6e-09
Processing of Capped Intron-Containing Pre-mRNA	6	32.9×	4e-07
mRNA Splicing - Major Pathway	8	29.1×	6e-09
Dengue Virus-Host Interactions	5	15.2×	2e-04
Metabolism of RNA	5	13.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	6	36.6×	1e-06

Disease & clinical

Genetic variants

Variant evidence for PCBP2: 55 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	4
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 1,129):

Position(s)	Effect	Δscore	Sites
12:53454712	acceptor_gain	1.0000
12:53454870–53454871	donor_loss	1.0000	4
12:53455345–53455346	acceptor_loss	1.0000	5
12:53455459–53455460	acceptor_loss	1.0000	5
12:53455494–53455495	donor_loss	1.0000	4
12:53455883–53455884	acceptor_loss	1.0000	6
12:53456002–53456003	donor_loss	1.0000	4
12:53459267	acceptor_gain	1.0000
12:53459270–53459271	acceptor_loss	1.0000	5
12:53459404–53459405	donor_loss	1.0000	5

AlphaMissense

1,433 missense substitutions predicted likely pathogenic (of 2,378 scored), across 289 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M20	9	0.987	1.000
M39	9	0.937	0.999
D82	8	0.993	0.998
F72	8	0.982	0.999
S27	8	0.971	0.999
H21	8	0.964	0.996
S43	8	0.958	0.999
F69	8	0.937	0.996
D136	8	0.923	0.996
D297	8	0.857	0.986
F193	8	0.772	0.939
H247	8	0.743	0.973
E143	7	0.999	1.000
R333	7	0.999	1.000
I29	7	0.998	1.000
E56	7	0.998	1.000
C109	7	0.998	1.000
I113	7	0.998	1.000
R101	7	0.996	1.000
I303	7	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.5e-07
Liver Hepatocellular Carcinoma (validation)	unfavorable	1.67e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	3.83e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	6.63e-05
Lung Adenocarcinoma (TCGA)	unfavorable	0.000947

Disease associations

OMIM: gene MIM:601210 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
neurodevelopmental disorder	Strong	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber

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

GWAS associations

6 associations:

Study	Trait	p-value
GCST004608_118	Granulocyte percentage of myeloid white cells	5e-23
GCST004609_173	Monocyte percentage of white cells	1e-22
GCST005956_63	Waist-to-hip ratio adjusted for BMI	4e-13
GCST005962_45	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7e-13
GCST005958_17	Waist-to-hip ratio adjusted for BMI (age >50)	1e-8
GCST005957_8	Waist-to-hip ratio adjusted for BMI (age <50)	6e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295826 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	5
Valproic Acid	affects expression, decreases expression	5
Arsenic Trioxide	increases expression, affects binding, decreases reaction, decreases expression	3
Arsenic	affects methylation, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression	2
Dronabinol	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	increases expression	1
coumarin	increases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
CD 437	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119037	Binding	Binding affinity to PCBP2 in human NCI-H358 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 210 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	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	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	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	COMPLETED	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
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
NCT03770832	Not specified	ACTIVE_NOT_RECRUITING	Wearable Sensors and Video Recordings to Monitor Motor Development
NCT03830879	Not specified	RECRUITING	Shenzhen Birth Cohort Study
NCT03835689	Not specified	COMPLETED	Strongest FamiliesTM Neurodevelopmental
NCT03882788	Not specified	COMPLETED	The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
NCT03922087	Not specified	COMPLETED	No-worry Baby Project
NCT03977259	Not specified	ACTIVE_NOT_RECRUITING	Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
NCT04043572	Not specified	UNKNOWN	The Biomarkers of Neurological Disease in Utero Study
NCT04096430	Not specified	RECRUITING	Evaluation of Effectiveness of Child-oriented Goal-setting in Paediatric Rehabilitation (the ENGAGE Approach)
NCT04108273	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children
NCT04201509	Not specified	COMPLETED	Validity of Neurocognitive Assessment Methods in Childhood ADHD
NCT04233775	Not specified	UNKNOWN	Altered Cerebral Growth and Development in Infants With Congenital Heart Disease
NCT04313283	Not specified	COMPLETED	Translating Peer-to-Peer Support Into a Clinical Setting