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
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001135653

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: 49 — 24 retained_intron, 22 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000372856, ENST00000372857, ENST00000372858, 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

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.

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

295 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2

miRNA regulators (miRDB)

44 targeting PABPC4, 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-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

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)

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): Q13310, A0A7I2V4L7, A0A7I2V4V6, A0A7I2V598, A0A7I2V5F4, A0A7I2V5W9, B1ANR0, B1ANR1, 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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 315, 319, 361, 364, 419, 432, 436, 454, 518, 530, 531, 584, 361, 375, 496, 140, 206, 304

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

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 (6): RNA processing (GO:0006396), RNA catabolic process (GO:0006401), translation (GO:0006412), blood coagulation (GO:0007596), regulation of mRNA stability (GO:0043488), myeloid cell development (GO:0061515)

GO Molecular Function (7): 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), mRNA binding (GO:0003729), 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

Rollup of top GO terms by namespace:

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
regulation of RNA stability	1
regulation of mRNA catabolic process	1
hemopoiesis	1
myeloid cell differentiation	1
nucleic acid binding	1
mRNA binding	1
poly-purine tract binding	1
poly-pyrimidine tract binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
protein-containing complex	1

Protein interactions and networks

STRING

2382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PABPC4	PABPN1	Q86U42	912
PABPC4	EIF4G1	Q04637	800
PABPC4	EIF4E	P06730	715
PABPC4	CSDE1	O75534	679
PABPC4	UPF1	Q92900	658
PABPC4	PABPC1	P11940	651
PABPC4	PAIP1	Q9H074	650
PABPC4	EIF4A1	P04765	643
PABPC4	DDX6	P26196	640
PABPC4	EIF4A2	Q14240	629
PABPC4	MOV10	Q9HCE1	604
PABPC4	TNRC6A	Q8NDV7	597
PABPC4	PAIP2	Q9BPZ3	559
PABPC4	RRM1	P23921	544
PABPC4	AGO2	Q9UKV8	543

IntAct

243 interactions, top by confidence:

A	B	Type	Score
PAIP1	PABPC1	psi-mi:“MI:0914”(association)	0.970
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
YBX1	SSB	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
N	RRP9	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
PAIP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
steC	SCD	psi-mi:“MI:0914”(association)	0.460
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
TOMM20	PABPC4	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	PABPC1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (632): PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1NHK4, A0AV96, O22173, O60506, P11940, P21187, P29341, P61286, Q13310, Q15233, Q1LZD9, Q32NN2, Q4KLH4, Q4R4J1, Q4V7D7, Q5R469, Q5R5P4, Q5R8F7, Q5R9H4, Q5RFL9, Q5W9D5, Q5W9D6, Q5W9D7, Q5YD48, Q5ZM16, Q66H68, Q6DEY7, Q6GR16, Q6IP09, Q6IRN2, Q6P0D0, Q7JJZ8, Q7TMK9, Q7TP47, Q8BHS3, Q8R326, Q8WXF1, Q91WT8, Q91XU1, Q923K9

Diamond homologs: A0A0D1DWZ5, A0JM51, A1CRM1, A1D4K4, A2A5N3, A2Q848, A3LXL0, A4IIM2, A4QUF0, A5DW14, F4HT49, O04319, O14102, O22173, O57406, O64380, O95319, O97018, P04147, P0CB38, P0CP46, P0CP47, P20965, P21187, P28659, P29558, P31209, P32588, P39697, P42731, P60047, P60048, P60049, P60050, Q08E07, Q09442, Q0CR95, Q0U1G2, Q13310, Q15427

SIGNOR signaling

2 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 211 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
Nonsense-Mediated Decay (NMD)	7	10.8×	3e-04
M-decay: degradation of maternal mRNAs by maternally stored factors	5	10.8×	3e-03
Dengue Virus Genome Translation and Replication	5	10.5×	4e-03
SARS-CoV-1 modulates host translation machinery	5	10.2×	4e-03
Translation initiation complex formation	8	10.1×	1e-04
Ribosomal scanning and start codon recognition	8	10.1×	1e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	12	9.4×	1e-06
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	14	9.1×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	5	26.4×	1e-04
stress granule assembly	6	19.2×	8e-05
mRNA stabilization	9	17.5×	1e-06
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	7	17.4×	2e-05
regulation of translational initiation	7	17.4×	2e-05
translational initiation	8	15.3×	2e-05
negative regulation of translation	14	14.6×	8e-10
intrinsic apoptotic signaling pathway	6	11.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1751 predictions. Top by Δscore:

Variant	Effect	Δscore
1:39561683:A:AC	donor_gain	1.0000
1:39561684:C:CC	donor_gain	1.0000
1:39561684:CGG:C	donor_gain	1.0000
1:39561691:T:A	donor_gain	1.0000
1:39561786:ACC:A	acceptor_loss	1.0000
1:39561788:C:CC	acceptor_gain	1.0000
1:39562067:GCTCA:G	donor_loss	1.0000
1:39562069:TCA:T	donor_loss	1.0000
1:39562070:CA:C	donor_loss	1.0000
1:39562071:A:AC	donor_gain	1.0000
1:39562072:C:CC	donor_gain	1.0000
1:39562072:C:CG	donor_loss	1.0000
1:39562199:TTCTC:T	acceptor_gain	1.0000
1:39562201:CTC:C	acceptor_gain	1.0000
1:39562202:TC:T	acceptor_gain	1.0000
1:39562203:CC:C	acceptor_gain	1.0000
1:39562203:CCTAT:C	acceptor_loss	1.0000
1:39562204:C:CC	acceptor_gain	1.0000
1:39562206:A:AC	acceptor_gain	1.0000
1:39562215:A:C	acceptor_gain	1.0000
1:39562321:AC:A	donor_gain	1.0000
1:39562322:CC:C	donor_gain	1.0000
1:39562322:CCCAG:C	donor_gain	1.0000
1:39562417:C:CG	acceptor_loss	1.0000
1:39562418:T:A	acceptor_loss	1.0000
1:39562425:C:CT	acceptor_gain	1.0000
1:39563212:CAT:C	donor_gain	1.0000
1:39563608:CCTCA:C	donor_loss	1.0000
1:39563609:CTCA:C	donor_loss	1.0000
1:39563610:TCAC:T	donor_loss	1.0000

AlphaMissense

4336 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:39561760:C:G	A625P	1.000
1:39561765:A:G	L623P	1.000
1:39561765:A:T	L623Q	1.000
1:39561768:A:T	V622D	1.000
1:39561772:C:G	A621P	1.000
1:39561777:G:T	A619D	1.000
1:39561778:C:G	A619P	1.000
1:39561778:C:T	A619T	1.000
1:39561780:T:A	E618V	1.000
1:39561781:C:T	E618K	1.000
1:39562073:C:A	K615N	1.000
1:39562073:C:G	K615N	1.000
1:39562075:T:C	K615E	1.000
1:39562083:A:G	L612P	1.000
1:39562083:A:T	L612H	1.000
1:39562101:A:G	L606S	1.000
1:39562104:A:C	M605R	1.000
1:39562110:A:G	L603P	1.000
1:39562113:A:G	L602P	1.000
1:39562113:A:T	L602Q	1.000
1:39562117:C:T	E601K	1.000
1:39562125:T:A	D598V	1.000
1:39562126:C:A	D598Y	1.000
1:39562126:C:G	D598H	1.000
1:39562128:A:T	I597K	1.000
1:39562131:T:A	E596V	1.000
1:39562132:C:T	E596K	1.000
1:39562134:A:C	L595R	1.000
1:39562134:A:G	L595P	1.000
1:39562134:A:T	L595Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000057139 (1:39570118 TCCA>T,TCCACCA), RS1000078619 (1:39564646 G>A), RS1000385134 (1:39565276 C>A), RS1000548596 (1:39574707 G>A,C), RS1000693709 (1:39564037 C>T), RS1000820414 (1:39563786 A>G), RS1000820493 (1:39569261 G>A), RS1000850017 (1:39569059 C>G,T), RS1000927522 (1:39575042 C>A,G), RS1001293349 (1:39564262 C>A), RS1001360247 (1:39574809 T>C), RS1001390014 (1:39575491 C>T), RS1001423998 (1:39569188 G>A), RS1001731863 (1:39569953 C>A,T), RS1001797644 (1:39575688 G>A,C,T)

Disease associations

OMIM: gene MIM:603407 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST000755_20	HDL cholesterol	4.000000e-10
GCST000965_11	C-reactive protein levels	6.000000e-11
GCST002223_48	HDL cholesterol	3.000000e-18
GCST002899_32	HDL cholesterol	8.000000e-10
GCST003680_13	C-reactive protein levels or HDL-cholesterol levels (pleiotropy)	3.000000e-15
GCST003681_1	C-reactive protein levels or triglyceride levels (pleiotropy)	2.000000e-13
GCST004232_21	HDL cholesterol levels	2.000000e-19
GCST004621_33	Red cell distribution width	2.000000e-16
GCST005776_8	High density lipoprotein cholesterol levels	1.000000e-06
GCST006227_2	Diastolic blood pressure	9.000000e-07
GCST006231_12	Mean arterial pressure	9.000000e-08
GCST006611_114	HDL cholesterol	1.000000e-36
GCST007611_13	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	7.000000e-09
GCST007614_8	C-reactive protein levels	8.000000e-13
GCST007615_6	C-reactive protein levels	3.000000e-14
GCST007656_12	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	3.000000e-11
GCST007692_88	Chronic obstructive pulmonary disease	5.000000e-10
GCST007923_25	Medication use (drugs used in diabetes)	2.000000e-08
GCST008070_107	HDL cholesterol levels	3.000000e-06
GCST008070_131	HDL cholesterol levels	5.000000e-07
GCST008070_63	HDL cholesterol levels	6.000000e-15
GCST008074_90	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-06
GCST008075_172	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-24
GCST008075_224	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-07
GCST008075_37	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-17
GCST008083_102	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-06
GCST008084_122	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-07
GCST008084_219	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-27
GCST008084_49	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-17
GCST008085_146	HDL cholesterol levels in current drinkers	4.000000e-11

EFO canonical traits (15, from GWAS)

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

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

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	increases abundance, increases expression, decreases expression	3
bisphenol S	decreases methylation, increases expression	2
Vehicle Emissions	increases abundance, increases expression	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)	increases expression, affects cotreatment	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)

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