PDCD2L

Summary

PDCD2L (programmed cell death 2 like, HGNC:28194) is a protein-coding gene on chromosome 19q13.11, encoding uS5 assembly chaperone PDCD2L (Q9BRP1). May function as a chaperone for ribosomal protein uS5; its function appears redundant to PDCD2.

Predicted to be involved in apoptotic process. Located in membrane.

Source: NCBI Gene 84306 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 79 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28194
Approved symbol	PDCD2L
Name	programmed cell death 2 like
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC13096
Ensembl gene	ENSG00000126249
Ensembl biotype	protein_coding
OMIM	615661
Entrez	84306

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 retained_intron, 2 protein_coding

ENST00000246535, ENST00000585821, ENST00000587065, ENST00000587385, ENST00000589589

RefSeq mRNA: 2 — MANE Select: NM_032346 NM_001353433, NM_032346

CCDS: CCDS12438

Canonical transcript exons

ENST00000246535 — 7 exons

Exon	Start	End
ENSE00000862680	34404399	34404538
ENSE00002759398	34425990	34426168
ENSE00003476662	34404649	34404815
ENSE00003570416	34413737	34413847
ENSE00003595430	34404930	34404990
ENSE00003624432	34421519	34421667
ENSE00003625680	34409161	34409510

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 95.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7753 / max 203.1966, expressed in 1749 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175143	16.0567	1745
175142	0.6644	283
175141	0.0542	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.61	gold quality
oocyte	CL:0000023	88.24	gold quality
gastrocnemius	UBERON:0001388	88.11	gold quality
muscle of leg	UBERON:0001383	88.07	gold quality
tibialis anterior	UBERON:0001385	87.45	silver quality
cortical plate	UBERON:0005343	85.91	gold quality
deltoid	UBERON:0001476	84.36	gold quality
quadriceps femoris	UBERON:0001377	84.25	gold quality
left ventricle myocardium	UBERON:0006566	84.16	silver quality
skeletal muscle tissue	UBERON:0001134	83.48	gold quality
prefrontal cortex	UBERON:0000451	83.25	gold quality
right testis	UBERON:0004534	83.20	gold quality
muscle tissue	UBERON:0002385	83.16	gold quality
apex of heart	UBERON:0002098	82.97	gold quality
ventricular zone	UBERON:0003053	82.97	gold quality
ganglionic eminence	UBERON:0004023	82.97	gold quality
vastus lateralis	UBERON:0001379	82.95	gold quality
left testis	UBERON:0004533	82.85	gold quality
testis	UBERON:0000473	82.76	gold quality
cerebellar cortex	UBERON:0002129	81.86	gold quality
cerebellar hemisphere	UBERON:0002245	81.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.20	gold quality
mucosa of transverse colon	UBERON:0004991	81.11	gold quality
body of pancreas	UBERON:0001150	81.08	gold quality
cerebellum	UBERON:0002037	80.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.93	gold quality
secondary oocyte	CL:0000655	80.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	11.13
E-MTAB-7303	no	938.23
E-ANND-3	no	2.61

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• To study the role of PDCD2_C domain in apoptosis, the cDNAs of two isoforms of PDCD2 and MGC13096 were cloned. PDCD2 (NM_002598) was over expressed when endothelial cells treated with leukotriene D4 or natural killer cells were activated by IL-2. (PMID:16311922)
• MGC13096 over-expression restrained proliferation of HEK293T cells. DNA/flow cytometry analysis showed that the over-expression of MGC13096 severely delays cell cycle progression at S phase. (PMID:17393540)
• Overexpression of PDCD2-like gene attenutates TNF-alpha release in Daudi cells (PMID:18486760)
• Findings uncover the existence of an extra-ribosomal complex consisting of PDCD2L, RPS2, and PRMT3 and support a role for PDCD2L in the late maturation of 40S ribosomal subunits. (PMID:27697862)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdcd2l	ENSDARG00000002754
mus_musculus	Pdcd2l	ENSMUSG00000002635
rattus_norvegicus	Pdcd2l	ENSRNOG00000021119
drosophila_melanogaster	trus	FBGN0038055

Paralogs (2): ZMYND12 (ENSG00000066185), PDCD2 (ENSG00000071994)

Protein

Protein identifiers

uS5 assembly chaperone PDCD2L — Q9BRP1 (reviewed: Q9BRP1)

Alternative names: Programmed cell death protein 2-like

All UniProt accessions (2): Q9BRP1, U3KQL1

UniProt curated annotations — full annotation on UniProt →

Function. May function as a chaperone for ribosomal protein uS5; its function appears redundant to PDCD2.

Subunit / interactions. Interacts with the 40S ribosomal protein RPS2/uS5; for putative chaperone function of PDC2L.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytosol.

Tissue specificity. Higher expression in lung, colon, mammary gland, cervix, stomach and small intestine.

Similarity. Belongs to the TSR4 family.

RefSeq proteins (2): NP_001340362, NP_115722* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007320	PDCD2_C	Domain
IPR052815	PDCD2-like_regulator	Family

Pfam: PF04194

UniProt features (6 total): modified residue 3, initiator methionine 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRP1-F1	75.93	0.40

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 (3): 2, 20, 22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): MODULE_255, MODULE_317, WEI_MYCN_TARGETS_WITH_E_BOX, MARZEC_IL2_SIGNALING_UP, GRADE_COLON_AND_RECTAL_CANCER_UP, NUYTTEN_EZH2_TARGETS_DN, YGCGYRCGC_UNKNOWN, MODULE_69, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, MODULE_37, STK33_DN, STK33_SKM_DN, NRF1_Q6, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_2H_DN, GSE13547_CTRL_VS_ANTI_IGM_STIM_BCELL_2H_DN

GO Biological Process (1): apoptotic process (GO:0006915)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

904 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDCD2L	GGN	Q86UU5	666
PDCD2L	PRMT3	O60678	591
PDCD2L	BYSL	Q13895	520
PDCD2L	ZNF277	Q9NRM2	503
PDCD2L	RPS2	P15880	451
PDCD2L	PABPN1	Q86U42	438
PDCD2L	EDRF1	Q3B7T1	430
PDCD2L	RPL4	P36578	429
PDCD2L	IQCF6	A8MYZ5	400
PDCD2L	PNO1	Q9NRX1	390
PDCD2L	LTV1	Q96GA3	387
PDCD2L	ZNF446	Q9NWS9	368
PDCD2L	TSR3	Q9UJK0	357
PDCD2L	HAGHL	Q6PII5	354
PDCD2L	XTBD1	Q96HQ2	349

IntAct

91 interactions, top by confidence:

A	B	Type	Score
PRMT3	RPS2	psi-mi:“MI:0914”(association)	0.810
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ITGB1BP2	PDCD2L	psi-mi:“MI:0915”(physical association)	0.690
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
KANK4	TRAPPC3	psi-mi:“MI:0914”(association)	0.640
FPR2	ARL6IP5	psi-mi:“MI:0914”(association)	0.640
NAP1L5	IQGAP1	psi-mi:“MI:0914”(association)	0.640
BRAF	VHL	psi-mi:“MI:0914”(association)	0.600
BRAF	MEN1	psi-mi:“MI:0914”(association)	0.600
PDCD2L	BRAF	psi-mi:“MI:0915”(physical association)	0.600
BRAF	PDCD2L	psi-mi:“MI:2364”(proximity)	0.600
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ARIH1	SPOP	psi-mi:“MI:0914”(association)	0.530
BMX	ARIH2	psi-mi:“MI:0914”(association)	0.530
NAP1L5	RPS2	psi-mi:“MI:0914”(association)	0.530
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530
PDCD2L	PRMT3	psi-mi:“MI:0914”(association)	0.530
KLHL10	HSPA8	psi-mi:“MI:0914”(association)	0.530

BioGRID (100): PDCD2L (Affinity Capture-MS), PDCD2L (Affinity Capture-MS), SRP14 (Affinity Capture-MS), PRMT3 (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), PCBP3 (Affinity Capture-MS), PDCD2L (Affinity Capture-MS), PDCD2L (Proximity Label-MS), PDCD2L (Proximity Label-MS), PDCD2L (Affinity Capture-MS), PDCD2L (Affinity Capture-MS), PRMT3 (Affinity Capture-MS), PDCD2L (Affinity Capture-MS), PDCD2L (Affinity Capture-MS), PCBP3 (Affinity Capture-MS)

ESM2 similar proteins: A2AA28, A2RRH5, A4FV42, A6NDL7, A7MCT6, B0K012, B2RYG8, D3YWP0, D3ZRW8, E1B8U2, J3S6Y1, P21964, P50747, Q0V8R7, Q1JP61, Q2TBI8, Q3SZD4, Q3U2J5, Q4VBE8, Q58DC7, Q5E9Y6, Q5RJL2, Q5VZV1, Q6DJF8, Q6GQ33, Q6P9U1, Q7Z624, Q80WC9, Q86XA0, Q8BNV1, Q8C436, Q8CDZ2, Q8IZ69, Q8N371, Q8R1C6, Q8WU66, Q920N2, Q96AZ1, Q96CB9, Q96RR1

Diamond homologs: P25040, P46718, P47816, P87156, Q09787, Q16342, Q2YDC9, Q67XW5, Q9BRP1, Q9SB51, Q5ZID2, Q8C5N5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	15.7×	4e-03
protein ubiquitination	11	5.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

960 predictions. Top by Δscore:

Variant	Effect	Δscore
19:34404524:C:G	donor_gain	1.0000
19:34413731:TTTTA:T	acceptor_loss	1.0000
19:34413732:TTTA:T	acceptor_loss	1.0000
19:34413733:TTAGC:T	acceptor_loss	1.0000
19:34413734:TAGCC:T	acceptor_loss	1.0000
19:34413735:A:AG	acceptor_gain	1.0000
19:34413735:AGC:A	acceptor_loss	1.0000
19:34413736:G:GT	acceptor_gain	1.0000
19:34413736:GC:G	acceptor_gain	1.0000
19:34413736:GCC:G	acceptor_gain	1.0000
19:34413736:GCCT:G	acceptor_gain	1.0000
19:34413736:GCCTT:G	acceptor_gain	1.0000
19:34421513:TCCTA:T	acceptor_loss	1.0000
19:34421516:TAGGT:T	acceptor_loss	1.0000
19:34421517:A:T	acceptor_loss	1.0000
19:34421518:GGT:G	acceptor_gain	1.0000
19:34421666:AGG:A	donor_loss	1.0000
19:34421667:GG:G	donor_loss	1.0000
19:34421668:G:GA	donor_loss	1.0000
19:34421669:T:G	donor_loss	1.0000
19:34424130:GGTTC:G	donor_gain	1.0000
19:34404520:C:T	donor_gain	0.9900
19:34404538:GGT:G	donor_loss	0.9900
19:34404539:G:GG	donor_gain	0.9900
19:34404539:G:T	donor_loss	0.9900
19:34404540:T:G	donor_loss	0.9900
19:34409329:G:GT	donor_gain	0.9900
19:34413843:TTGAG:T	donor_loss	0.9900
19:34413844:TGAG:T	donor_loss	0.9900
19:34413846:AGGTA:A	donor_loss	0.9900

AlphaMissense

2357 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:34413807:T:C	F253L	0.992
19:34413809:C:A	F253L	0.992
19:34413809:C:G	F253L	0.992
19:34426004:T:C	F321L	0.990
19:34426006:T:A	F321L	0.990
19:34426006:T:G	F321L	0.990
19:34413808:T:C	F253S	0.987
19:34413847:G:C	R266T	0.986
19:34413847:G:T	R266M	0.986
19:34404757:C:A	R73S	0.985
19:34421626:T:A	L302H	0.985
19:34426037:A:C	S332R	0.985
19:34426039:T:A	S332R	0.985
19:34426039:T:G	S332R	0.985
19:34404732:C:G	C64W	0.984
19:34421618:G:C	E299D	0.984
19:34421618:G:T	E299D	0.984
19:34421519:G:C	R266S	0.983
19:34421519:G:T	R266S	0.983
19:34426028:T:C	C329R	0.983
19:34404518:A:C	S30R	0.982
19:34404520:C:A	S30R	0.982
19:34404520:C:G	S30R	0.982
19:34426026:C:A	T328K	0.982
19:34421520:T:G	Y267D	0.980
19:34404461:G:C	G11R	0.979
19:34404758:G:C	R73P	0.979
19:34404943:C:A	R97S	0.979
19:34404944:G:C	R97P	0.979
19:34413798:T:C	F250L	0.978

dbSNP variants (sampled 300 via entrez): RS1000118141 (19:34417244 A>C,G), RS1000421670 (19:34423490 T>C), RS1000547548 (19:34412095 T>C), RS1000573407 (19:34410820 C>G,T), RS1000630128 (19:34412367 A>T), RS1000683230 (19:34406258 G>A), RS1000840725 (19:34416204 A>G), RS1000870355 (19:34405714 A>G), RS1000938999 (19:34422950 C>A), RS1000976873 (19:34424747 T>TTG), RS1001107560 (19:34412597 A>C,G), RS1001212169 (19:34421927 T>C), RS1001264357 (19:34421547 T>C,G), RS1001458692 (19:34414978 T>C), RS1001599387 (19:34406112 G>A)

Disease associations

OMIM: gene MIM:615661 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010796_5374	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725169 (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

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

pChembl	Type	Value	Unit	Molecule
5.36	Kd	4322	nM	CHEMBL3752910
5.35	ED50	4491	nM	CHEMBL3752910
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149906: Binding affinity to human PDCD2L incubated for 45 mins by Kinobead based pull down assay	kd	4.3216	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178930: Inhibition of PDCD2L (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases expression	2
beauvericin	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-phenylbutyric acid	decreases expression	1
cylindrospermopsin	increases expression	1
jinfukang	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Cadmium	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Phenobarbital	affects expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652948	Binding	Binding affinity to human PDCD2L incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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