PABPC4

Summary

PABPC4 (poly(A) binding protein cytoplasmic 4, HGNC:8557) is a protein-coding gene on chromosome 1p34.3, encoding Polyadenylate-binding protein 4 (Q13310). Binds the poly(A) tail of mRNA.

Poly(A)-binding proteins (PABPs) bind to the poly(A) tail present at the 3-prime ends of most eukaryotic mRNAs. PABPC4 or IPABP (inducible PABP) was isolated as an activation-induced T-cell mRNA encoding a protein. Activation of T cells increased PABPC4 mRNA levels in T cells approximately 5-fold. PABPC4 contains 4 RNA-binding domains and proline-rich C terminus. PABPC4 is localized primarily to the cytoplasm. It is suggested that PABPC4 might be necessary for regulation of stability of labile mRNA species in activated T cells. PABPC4 was also identified as an antigen, APP1 (activated-platelet protein-1), expressed on thrombin-activated rabbit platelets. PABPC4 may also be involved in the regulation of protein translation in platelets and megakaryocytes or may participate in the binding or stabilization of polyadenylates in platelet dense granules. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. This protein has also been found to interact with coronavirus nucleocapsid proteins and is thought to inhibit coronavirus replication.

Source: NCBI Gene 8761 — RefSeq curated summary.

At a glance

• GWAS associations: 51 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 61 total
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 31 tissues, sQTL in 22 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.31 (highly constrained)
• MANE Select transcript: NM_001135653
• Notable: 61 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8557
Approved symbol	PABPC4
Name	poly(A) binding protein cytoplasmic 4
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	iPABP, APP-1
Ensembl gene	ENSG00000090621
Ensembl biotype	protein_coding
OMIM	603407
Entrez	8761

Gene structure

Transcript identifiers

Ensembl transcripts: 67 — 27 protein_coding, 24 retained_intron, 15 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000372858

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

ENST00000372858, ENST00000372856, ENST00000372857, ENST00000372862, ENST00000421687, ENST00000437136, ENST00000451091, ENST00000461578, ENST00000468476, ENST00000470443, ENST00000474378, ENST00000477556, ENST00000482028, ENST00000483770, ENST00000484555, ENST00000492468, ENST00000492519, ENST00000513632, ENST00000525045, ENST00000525669, ENST00000525751, ENST00000527718, ENST00000529216, ENST00000530186, ENST00000531243, ENST00000676523, ENST00000676859, ENST00000676863, ENST00000677006, ENST00000677244, ENST00000677548, ENST00000677609, ENST00000677644, ENST00000677708, ENST00000677860, ENST00000678028, ENST00000678287, ENST00000678469, ENST00000678625, ENST00000678894, ENST00000678980, ENST00000679246, ENST00000916728, ENST00000916729, ENST00000916730, ENST00000916731, ENST00000916732, ENST00000966511, ENST00000966512, ENST00001006754, ENST00001010119, ENST00001010120, ENST00001010121, ENST00001010122, ENST00001010123, ENST00001010124, ENST00001010125, ENST00001010126, ENST00001010127, ENST00001010128, ENST00001010129, ENST00001010130, ENST00001010131, ENST00001010132, ENST00001010133, ENST00001010135, ENST00001144681

RefSeq mRNA: 3 — MANE Select: NM_001135653 NM_001135653, NM_001135654, NM_003819

CCDS: CCDS438, CCDS44114, CCDS44115

Canonical transcript exons

ENST00000372858 — 16 exons

Exon	Start	End
ENSE00000767832	39563836	39563922
ENSE00001328393	39562323	39562416
ENSE00001723376	39571234	39571349
ENSE00001755773	39564423	39564542
ENSE00001914889	39575759	39576790
ENSE00003466784	39562073	39562203
ENSE00003543268	39564686	39564773
ENSE00003548424	39569595	39569689
ENSE00003550009	39568802	39568939
ENSE00003557899	39560816	39561122
ENSE00003590827	39567751	39567846
ENSE00003595808	39565106	39565378
ENSE00003598772	39561685	39561787
ENSE00003651660	39569863	39570002
ENSE00003788728	39572393	39572586
ENSE00003790975	39563614	39563741

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 152.9412 / max 9560.3970, expressed in 1828 samples.

Highest expression (Bgee): body of pancreas, gastrocnemius, muscle of leg, hindlimb stylopod muscle, muscle organ.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PABPC4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 22 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 53 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.2e-36	-0.43	1:39570256:G:T
Skin Sun Exposed Lower leg	eqtl	7.7e-33	-0.32	1:39570256:G:T
Skin Sun Exposed Lower leg	sqtl	5.6e-28	-0.63	1:39570256:G:T
Artery Tibial	eqtl	6.8e-27	-0.28	1:39575699:G:GA
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-26	-0.30	1:39570256:G:T
Esophagus Mucosa	eqtl	1.9e-26	-0.41	1:39570256:G:T
Adipose Subcutaneous	eqtl	1.5e-21	-0.26	1:39557105:C:G
Skin Not Sun Exposed Suprapubic	sqtl	1.1e-20	-0.58	1:39570256:G:T
Adipose Subcutaneous	sqtl	5.4e-18	-0.49	1:39578100:G:A
Breast Mammary Tissue	eqtl	2.6e-17	-0.21	1:39544563:T:C
Nerve Tibial	sqtl	7.3e-17	-0.51	1:39570014:C:T
Nerve Tibial	eqtl	2.7e-16	-0.19	1:39570014:C:T
Thyroid	eqtl	4.6e-15	-0.26	1:39578080:C:G
Muscle Skeletal	eqtl	5.9e-14	-0.24	1:39570014:C:T
Whole Blood	eqtl	1.1e-12	-0.13	1:39562508:A:G
Lung	eqtl	1.6e-12	-0.22	1:39586436:C:G
Adipose Visceral Omentum	eqtl	2.0e-12	-0.17	1:39578100:G:A
Artery Tibial	sqtl	9.6e-12	+0.48	1:39570256:G:T
Esophagus Mucosa	sqtl	2.2e-11	+0.46	1:39570256:G:T
Esophagus Muscularis	eqtl	2.3e-11	-0.19	1:39591871:A:G

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
11862	135.7111	1828
11863	7.9664	1754
11864	5.2659	1621
11860	1.5366	836
11861	0.9769	563
11858	0.8951	589
11865	0.2334	110
11866	0.2045	105
11859	0.1512	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.43	gold quality
gastrocnemius	UBERON:0001388	99.21	gold quality
muscle of leg	UBERON:0001383	99.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.02	gold quality
muscle organ	UBERON:0001630	98.98	gold quality
secondary oocyte	CL:0000655	98.95	gold quality
gluteal muscle	UBERON:0002000	98.94	gold quality
skeletal muscle tissue	UBERON:0001134	98.77	gold quality
vastus lateralis	UBERON:0001379	98.72	gold quality
quadriceps femoris	UBERON:0001377	98.69	gold quality
body of tongue	UBERON:0011876	98.68	gold quality
triceps brachii	UBERON:0001509	98.56	gold quality
left ovary	UBERON:0002119	98.56	gold quality
tibialis anterior	UBERON:0001385	98.55	gold quality
muscle tissue	UBERON:0002385	98.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.49	gold quality
right testis	UBERON:0004534	98.49	gold quality
body of stomach	UBERON:0001161	98.47	gold quality
right ovary	UBERON:0002118	98.41	gold quality
left testis	UBERON:0004533	98.39	gold quality
biceps brachii	UBERON:0001507	98.36	gold quality
right atrium auricular region	UBERON:0006631	98.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.23	gold quality
colonic epithelium	UBERON:0000397	98.22	gold quality
sural nerve	UBERON:0015488	98.21	gold quality
cardiac atrium	UBERON:0002081	98.20	gold quality
deltoid	UBERON:0001476	98.18	gold quality
pancreas	UBERON:0001264	98.17	gold quality
stomach	UBERON:0000945	98.03	gold quality
oocyte	CL:0000023	97.90	gold quality
fundus of stomach	UBERON:0001160	97.90	gold quality
diaphragm	UBERON:0001103	97.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.86	gold quality
heart left ventricle	UBERON:0002084	97.86	gold quality
testis	UBERON:0000473	97.82	gold quality
cardiac ventricle	UBERON:0002082	97.79	gold quality
heart	UBERON:0000948	97.69	gold quality
lower esophagus mucosa	UBERON:0035834	97.67	gold quality
peritoneum	UBERON:0002358	97.64	gold quality
omental fat pad	UBERON:0010414	97.64	gold quality
body of uterus	UBERON:0009853	97.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.57	gold quality
apex of heart	UBERON:0002098	97.56	gold quality
left uterine tube	UBERON:0001303	97.51	gold quality
right coronary artery	UBERON:0001625	97.51	gold quality
stromal cell of endometrium	CL:0002255	97.49	gold quality
left adrenal gland cortex	UBERON:0035825	97.48	gold quality
right adrenal gland cortex	UBERON:0035827	97.45	gold quality
urinary bladder	UBERON:0001255	97.44	gold quality
left adrenal gland	UBERON:0001234	97.41	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.41	gold quality
bone marrow cell	CL:0002092	97.37	gold quality
adrenal gland	UBERON:0002369	97.36	gold quality
tongue	UBERON:0001723	97.35	gold quality
endocervix	UBERON:0000458	97.34	gold quality
adrenal cortex	UBERON:0001235	97.34	gold quality
popliteal artery	UBERON:0002250	97.34	gold quality
tibial artery	UBERON:0007610	97.34	gold quality
ovary	UBERON:0000992	97.33	gold quality
islet of Langerhans	UBERON:0000006	97.32	gold quality
right adrenal gland	UBERON:0001233	97.32	gold quality
right lung	UBERON:0002167	97.32	gold quality
minor salivary gland	UBERON:0001830	97.28	gold quality
right uterine tube	UBERON:0001302	97.26	gold quality
ventricular zone	UBERON:0003053	97.25	gold quality
upper lobe of left lung	UBERON:0008952	97.20	gold quality
lower esophagus	UBERON:0013473	97.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.15	gold quality
left coronary artery	UBERON:0001626	97.14	gold quality
ectocervix	UBERON:0012249	97.14	gold quality
adrenal tissue	UBERON:0018303	97.13	gold quality
upper lobe of lung	UBERON:0008948	97.12	gold quality
monocyte	CL:0000576	97.11	gold quality
cartilage tissue	UBERON:0002418	97.10	gold quality
saliva-secreting gland	UBERON:0001044	97.07	gold quality
gall bladder	UBERON:0002110	97.05	gold quality
mononuclear cell	CL:0000842	97.04	gold quality
tibial nerve	UBERON:0001323	97.02	gold quality
leukocyte	CL:0000738	97.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.01	gold quality
lymph node	UBERON:0000029	97.00	gold quality
mucosa of stomach	UBERON:0001199	96.99	gold quality
cardia of stomach	UBERON:0001162	96.96	gold quality
skin of abdomen	UBERON:0001416	96.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.95	gold quality
coronary artery	UBERON:0001621	96.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.89	gold quality
aorta	UBERON:0000947	96.87	gold quality
superior surface of tongue	UBERON:0007371	96.86	gold quality
skin of leg	UBERON:0001511	96.84	gold quality
sigmoid colon	UBERON:0001159	96.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.83	gold quality
right lobe of thyroid gland	UBERON:0001119	96.76	gold quality
pylorus	UBERON:0001166	96.76	gold quality
esophagus	UBERON:0001043	96.74	gold quality
parotid gland	UBERON:0001831	96.73	gold quality
transverse colon	UBERON:0001157	96.72	gold quality
spleen	UBERON:0002106	96.67	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	78.33
E-CURD-46	yes	41.04
E-GEOD-134144	yes	28.36
E-GEOD-81547	yes	22.90
E-ANND-3	yes	20.05
E-HCAD-11	yes	19.24
E-MTAB-9543	yes	13.89
E-MTAB-10553	yes	9.61

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	448.1	medium
Pancreas	tissue	296.8	high
Tongue	tissue	228.5
Heart muscle	tissue	84.0	medium
Ovary	tissue	73.3	high
Bone marrow	tissue	72.5	medium
Choroid plexus	tissue	70.0
Stomach 1	tissue	67.5	medium
Testis	tissue	66.0	high
Urinary bladder	tissue	62.6	medium
Tonsil	tissue	61.1	medium
Lymph node	tissue	60.9	medium
Adipose tissue	tissue	60.1	low
Liver	tissue	56.1	low
Hippocampus	tissue	54.3	medium
Locus coeruleus	tissue	52.0
Spleen	tissue	50.0	low
Adrenal gland	tissue	49.4	medium
Appendix	tissue	48.3	medium
Salivary gland	tissue	48.1	low
Vagina	tissue	47.9	medium
Cervix	tissue	47.0	low
Nucleus accumbens	tissue	46.9
Placenta	tissue	46.6	high
Esophagus	tissue	45.4	medium
Smooth muscle	tissue	43.1	medium
Fallopian tube	tissue	42.3	medium
Endometrium 1	tissue	41.8	medium
Colon	tissue	40.8	medium
Epididymis	tissue	38.9	medium
Breast	tissue	38.1	medium
Gallbladder	tissue	37.3	medium
Lung	tissue	35.9	low
Small intestine	tissue	35.2	low
Seminal vesicle	tissue	34.7	medium
Prostate	tissue	34.6	low
Duodenum	tissue	34.5	low
Postcentral gyrus	tissue	32.6
Rectum	tissue	30.7	medium
Thymus	tissue	30.5
Thyroid gland	tissue	30.3	medium
Skin 1	tissue	30.0	not detected
Kidney	tissue	28.8	medium
Parathyroid gland	tissue	26.3	medium
Pituitary gland	tissue	23.3
Prefrontal cortex	tissue	23.3
Cerebral cortex	tissue	23.3	medium
Occipital cortex	tissue	21.7
Retina	tissue	21.3
Motor cortex	tissue	20.9
Somatosensory cortex	tissue	20.8
Temporal cortex	tissue	20.8
Hippocampal formation	tissue	20.6
Entorhinal cortex	tissue	20.6
Amygdala	tissue	20.2
Frontal cortex	tissue	19.8
Insular cortex	tissue	19.8
Basal ganglia	tissue	19.5	medium
Superior colliculi	tissue	19.3
Ventral forebrain	tissue	19.2

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Lateral funiculus (white matter) (80.2), Temporal white matter (75.1), Nucleus ambiguus (75.0), Anterior thalamic nucleus, ventral (74.3), Angular gyrus (white matter) (71.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2

miRNA regulators (miRDB)

Targeting PABPC4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 44 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
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-548AT-5P	99.96	70.83	2666
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-548AT-3P	98.37	64.98	580

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.311, missense Z 3.32 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000372858 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈2% 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
1:39,561,701–39,562,106	29 / 51.6	0.56	no
1:39,562,107–39,562,159	0 / 21.1	0.00	yes (p 4.3e-06)
1:39,562,160–39,565,215	277 / 301.8	0.92	no
1:39,565,216–39,575,951	304 / 478.9	0.63	no

Literature-anchored findings (GeneRIF, showing 8)

• RNA binding masks nuclear import signals within the cytoplasmic poly(A) binding protein RNA recognition motifs, thereby ensuring ef fi cient cytoplasmic retention of this protein in normal cells (PMID:21646427)
• Nuclear relocalisation of cytoplasmic poly(A)-binding proteins PABP1 and PABP4 in response to UV irradiation reveals mRNA-dependent export (PMID:21940797)
• PABPC4 is highly expressed in human colorectal cancer. (PMID:22884093)
• although function of PABPN1 may be compensated by nuclear translocation of PABP4 and perhaps by increase the cytoplasmic abundance of PABP5, these were not sufficient to prevent apoptosis of cells. PABPN1 may have an anti apoptotic role in mammalian cells (PMID:23300856)
• The PABPC4 rs4660293 SNP is associated with serum lipid levels. (PMID:26005159)
• A novel long non-coding RNA RP11-286H15.1 represses hepatocellular carcinoma progression by promoting ubiquitination of PABPC4. (PMID:33259899)
• Gene variants of coagulation related proteins that interact with SARS-CoV-2. (PMID:33730015)
• PABPC4 Broadly Inhibits Coronavirus Replication by Degrading Nucleocapsid Protein through Selective Autophagy. (PMID:34612687)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pabpc4	ENSDARG00000059259
mus_musculus	Pabpc4	ENSMUSG00000011257
rattus_norvegicus	Pabpc4	ENSRNOG00000015642
rattus_norvegicus	Pabpc4-ps1	ENSRNOG00000028592

Paralogs (24): ELAVL1 (ENSG00000066044), PABPC1 (ENSG00000070756), RBMS2 (ENSG00000076067), PABPC1L (ENSG00000101104), ELAVL2 (ENSG00000107105), RBM24 (ENSG00000112183), TARDBP (ENSG00000120948), HNRNPR (ENSG00000125944), RBM38 (ENSG00000132819), SYNCRIP (ENSG00000135316), SF3B4 (ENSG00000143368), RBMS3 (ENSG00000144642), PABPC3 (ENSG00000151846), RBMS1 (ENSG00000153250), RBM45 (ENSG00000155636), ELAVL4 (ENSG00000162374), PABPC5 (ENSG00000174740), PUF60 (ENSG00000179950), PABPC1L2B (ENSG00000184388), PABPC1L2A (ENSG00000186288), RBM34 (ENSG00000188739), ELAVL3 (ENSG00000196361), RBM14 (ENSG00000239306), PABPC4L (ENSG00000254535)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2385206) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased heart weight	1
abnormal spine curvature	1
decreased circulating cholesterol level	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
Cryptococcus deneoformans JEC21	P0CP46	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CP47	100.0%	Diamond
Gorilla gorilla gorilla	P60047	100.0%	Diamond
Hylobates lar	P60048	100.0%	Diamond
Pan troglodytes	P60049	100.0%	Diamond
Pongo pygmaeus	P60050	100.0%	Diamond
Bos taurus	P61286	100.0%	Diamond
Pongo abelii	Q5R6W3	100.0%	Diamond
Gallus gallus	Q7T2T1	99.8%	Diamond
Macaca mulatta	Q7JGR2	99.7%	Diamond
Aspergillus fischeri NRRL 181	A1D4K4	98.7%	Diamond
Aspergillus fumigatus Af293	Q4WK03	98.7%	Diamond
Macaca fascicularis	Q95KI0	97.9%	Diamond
Xenopus tropicalis	Q28HE9	96.7%	Diamond
Xenopus laevis	Q6PF35	96.7%	Diamond
Nicotiana plumbaginifolia	P49313	92.8%	Diamond
Nicotiana sylvestris	Q08935	92.8%	Diamond
Drosophila melanogaster	P92204	92.2%	Diamond
Drosophila virilis	Q95ZE9	92.2%	Diamond
Musca domestica	O17310	90.6%	Diamond
Chrysomya rufifacies	O97018	90.6%	Diamond
Aspergillus clavatus NRRL 1	A1CRM1	89.5%	Diamond
Aspergillus niger CBS 513.88	A2Q848	89.0%	Diamond
Arabidopsis thaliana	Q03251	87.0%	Diamond
Aspergillus terreus NIH2624	Q0CR95	87.0%	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
HEYL	protein-coding	26508
BMP8A	protein-coding	353500
SNORA55	snoRNA	677834
NT5C1A	protein-coding	84618
PABPC4-AS1	ncRNA	101929516
HPCAL4	protein-coding	51440
MACF1	protein-coding	23499

Protein

Protein identifiers

Polyadenylate-binding protein 4 — Q13310 (reviewed: Q13310)

Alternative names: Activated-platelet protein 1, Inducible poly(A)-binding protein

All UniProt accessions (14): A0A7I2V4L7, A0A7I2V4V6, A0A7I2V598, A0A7I2V5F4, A0A7I2V5W9, B1ANR0, B1ANR1, Q13310, H0Y5F5, H0Y6X6, H0YCC8, H0YEQ8, H0YER0, H0YEU6

UniProt curated annotations — full annotation on UniProt →

Function. Binds the poly(A) tail of mRNA. Binds to SMIM26 mRNA and plays a role in its post-transcriptional regulation. May be involved in cytoplasmic regulatory processes of mRNA metabolism. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo.

Subunit / interactions. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with NFX1. Interacts with ZFC3H1 in a RNase-sensitive manner.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at low levels in resting normal T cells; following T-cell activation, however, mRNA levels are rapidly up-regulated.

Post-translational modifications. Arg-518 is dimethylated, probably to asymmetric dimethylarginine.

Similarity. Belongs to the polyadenylate-binding protein type-1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13310-1	1	yes
Q13310-2	2
Q13310-3	3

RefSeq proteins (3): NP_001129125, NP_001129126, NP_003810 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002004	PABP_HYD_C	Domain
IPR003954	RRM_euk-type	Domain
IPR006515	PABP_1234	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034364	PABP_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036053	PABP-dom	Homologous_superfamily
IPR045305	RRM2_I_PABPs	Domain

Pfam: PF00076, PF00658

UniProt features (29 total): modified residue 16, domain 5, cross-link 2, splice variant 2, chain 1, sequence variant 1, sequence conflict 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13310-F1	76.70	0.46

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH supported · IF enhanced

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 (18)

Type	Positions
Phosphoserine	315, 319, 531, 584, 206
N6,n6-dimethyllysine	361
Phosphotyrosine	364, 140
Omega-n-methylarginine	419, 432, 436, 454, 530, 496
Dimethylated arginine	518
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	361, 375
Phosphothreonine	304

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 273 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_DNMT1, GRUETZMANN_PANCREATIC_CANCER_DN, PAX4_01, MORF_RRM1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, MORF_HDAC2, HASLINGER_B_CLL_WITH_11Q23_DELETION, USF_C, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_DN

GO Biological Process (4): RNA processing (GO:0006396), RNA catabolic process (GO:0006401), translation (GO:0006412), blood coagulation (GO:0007596)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), poly(A) binding (GO:0008143), poly(U) RNA binding (GO:0008266), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), ribonucleoprotein complex (GO:1990904)

GO top-level categories

26 GO namespaces:

Category	Terms
binding	2
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
hemostasis	1
wound healing	1
coagulation	1
nucleic acid binding	1
mRNA binding	1
poly-purine tract binding	1
poly-pyrimidine tract binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	direct assay
cytoplasmic stress granule	CC	direct assay
cytosol	CC	direct assay
nucleus	CC	direct assay
ribonucleoprotein complex	CC	direct assay
RNA binding	MF	high-throughput assay
poly(A) binding	MF	direct assay
poly(U) RNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 1,707 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PABPC4	PABPN1	Q86U42	837
PABPC4	PAIP1	Q9H074	639
PABPC4	RRM1	P23921	529
PABPC4	EIF4G1	Q04637	481
PABPC4	UPF1	Q92900	459
PABPC4	DDX6	P26196	427
PABPC4	EIF4A1	P04765	414
PABPC4	XRN1	Q8IZH2	412
PABPC4	EIF4A2	Q14240	398
PABPC4	SRP9	P49458	396
PABPC4	EIF4E	P06730	396
PABPC4	FXR2	P51116	394
PABPC4	FXR1	P51114	388
PABPC4	DHX34	Q14147	370
PABPC4	ELSPBP1	Q96BH3	370
PABPC4	SYT3	Q9BQG1	370

IntAct

Human interaction partners of PABPC4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAZ	physical association	0.590	2
PHLDA1	physical association	0.510	2
SRPK2	physical association	0.480	1
TOMM20	physical association	0.400	1
SMAD9	physical association	0.370	1
HNRNPR	association	0.350	1
ARF6	physical association	0.000	1
HNF4A	physical association	0.000	1
IKBKE	physical association	0.000	1
PINX1	physical association	0.000	1
PPM1B	physical association	0.000	1
PUF60	physical association	0.000	1
TNFRSF10D	physical association	0.000	1
XRN1	physical association	0.000	1

BioGRID (652 interactions; top human partners by supporting records in a sample of 600 records): PABPC1 (Proximity Label-MS; 14 records), ATXN2 (Co-fractionation; 5 records), G3BP1 (Co-fractionation; 5 records), PABPC5 (Cross-Linking-MS (XL-MS); 4 records), PAIP1 (Proximity Label-MS; 4 records), TARDBP (Cross-Linking-MS (XL-MS); 4 records), CALCOCO2 (Affinity Capture-Western; 3 records), EZH2 (Affinity Capture-MS; 3 records), LARP1 (Affinity Capture-MS; 3 records), MKRN1 (Affinity Capture-MS; 3 records), MKRN3 (Affinity Capture-MS; 3 records), PABPC3 (Cross-Linking-MS (XL-MS); 3 records), PARK2 (Affinity Capture-MS; 3 records), SYNCRIP (Proximity Label-MS; 3 records), TRIM37 (Affinity Capture-MS; 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
PABPC4	“up-regulates activity”	NFX1	binding
PABPC4	“up-regulates quantity by stabilization”	“messenger RNA”	binding

Disease & clinical

Genetic variants

Variant evidence for PABPC4: 61 ClinVar records (0 pathogenic / likely pathogenic); 51 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 960):

Position(s)	Effect	Δscore	Sites
1:39561691	donor_gain	1.0000
1:39561788–39561789	acceptor_loss	1.0000	5
1:39562071–39562072	donor_loss	1.0000	5
1:39562204	acceptor_loss	1.0000
1:39562215	acceptor_gain	1.0000
1:39562417–39562418	acceptor_loss	1.0000	5
1:39563612–39563613	donor_loss	1.0000	5
1:39563742–39563743	acceptor_gain	1.0000	2
1:39563742–39563743	acceptor_loss	1.0000	4
1:39564421–39564422	donor_loss	1.0000	5

AlphaMissense

2,740 missense substitutions predicted likely pathogenic (of 4,336 scored), across 533 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
M593	9	0.999	1.000
M85	9	0.997	1.000
M326	9	0.997	1.000
M161	9	0.987	0.999
M353	9	0.987	1.000
M158	9	0.959	0.998
M72	9	0.932	0.999
M605	9	0.914	1.000
M570	9	0.890	0.999
N300	8	1.000	1.000
F337	8	1.000	1.000
F31	8	0.999	1.000
D45	8	0.999	1.000
D90	8	0.999	1.000
N100	8	0.999	1.000
D117	8	0.999	1.000
F119	8	0.999	1.000
H144	8	0.999	1.000
F235	8	0.999	1.000
N295	8	0.999	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 Papillary Cell Carcinoma (TCGA)	unfavorable	4.08e-07
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.56e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000316
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000735
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000965

Disease associations

OMIM: gene MIM:603407 | disease phenotypes:

GWAS associations

showing 30 of 51 associations:

Study	Trait	p-value
GCST010242_70	HDL cholesterol levels	1e-79
GCST010241_161	Apolipoprotein A1 levels	6e-66
GCST90002390_555	Mean corpuscular hemoglobin	5e-37
GCST006611_114	HDL cholesterol	1e-36
GCST90002404_210	Red cell distribution width	1e-27
GCST008084_176	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4e-27
GCST010244_80	Triglyceride levels	9e-26
GCST008075_174	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4e-24
GCST90002392_634	Mean corpuscular volume	1e-22
GCST90002391_9	Mean corpuscular hemoglobin concentration	3e-20
GCST004232_86	HDL cholesterol levels	2e-19
GCST002223_48	HDL cholesterol	3e-18
GCST008084_14	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-17
GCST009602_25	Metabolic syndrome	4e-17
GCST008075_89	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5e-17
GCST008085_190	HDL cholesterol levels in current drinkers	5e-17
GCST004621_113	Red cell distribution width	2e-16
GCST010702_177	Subcortical volume (MOSTest)	7e-16
GCST003680_12	C-reactive protein levels or HDL-cholesterol levels (pleiotropy)	3e-15
GCST008070_72	HDL cholesterol levels	6e-15
GCST007615_67	C-reactive protein levels	3e-14
GCST003681_13	C-reactive protein levels or triglyceride levels (pleiotropy)	2e-13
GCST007614_37	C-reactive protein levels	8e-13
GCST010696_5	Cortical thickness (min-P)	9e-12
GCST007656_10	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	3e-11
GCST008085_6	HDL cholesterol levels in current drinkers	4e-11
GCST000965_11	C-reactive protein levels	6e-11
GCST011122_2	Walking pace	6e-11
GCST010703_59	Brain morphology (MOSTest)	9e-11
GCST009368_30	HDL cholesterol levels x long total sleep time interaction (2df test)	1e-10

EFO canonical traits (from GWAS)

15 canonical traits:

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004458	C-reactive protein measurement
EFO:0004530	triglyceride measurement
EFO:0009188	Red cell distribution width
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0009924	Drugs used in diabetes use measurement
EFO:0004329	alcohol drinking
EFO:0006781	coffee consumption measurement
EFO:0000195	metabolic syndrome
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5333 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.03	IC50	9300	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 12 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178515: Inhibition of PABPC4 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	9.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression	4
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol S	decreases methylation, increases expression	2
Vehicle Emissions	increases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
methylparaben	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cadmium acetate	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Diuron	decreases 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
CHEMBL1041815	Binding	Inhibition of APP1 at 10 uM	Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis. — *J Med Chem*

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TB83	HAP1 PABPC4 (-) 1	Cancer cell line	Male
CVCL_TB84	HAP1 PABPC4 (-) 2	Cancer cell line	Male
CVCL_TB85	HAP1 PABPC4 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PABPC4 across ~30M SureChEMBL compounds — explore on Sugi Predict.