PDCD1LG2

Summary

PDCD1LG2 (programmed cell death 1 ligand 2, HGNC:18731) is a protein-coding gene on chromosome 9p24.1, encoding Programmed cell death 1 ligand 2 (Q9BQ51). Plays a critical role in induction and maintenance of immune tolerance to self.

Involved in negative regulation of activated T cell proliferation; negative regulation of interleukin-10 production; and negative regulation of type II interferon production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. Biomarker of pulmonary tuberculosis.

Source: NCBI Gene 80380 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 5 total — 1 pathogenic
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_025239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18731
Approved symbol	PDCD1LG2
Name	programmed cell death 1 ligand 2
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	PD-L2, Btdc, PDL2, bA574F11.2, CD273, B7-DC, B7DC
Ensembl gene	ENSG00000197646
Ensembl biotype	protein_coding
OMIM	605723
Entrez	80380

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000397747, ENST00000861551, ENST00000965244, ENST00000965245

RefSeq mRNA: 1 — MANE Select: NM_025239 NM_025239

CCDS: CCDS6465

Canonical transcript exons

ENST00000397747 — 7 exons

Exon	Start	End
ENSE00000688198	5549335	5549604
ENSE00000688201	5557618	5557752
ENSE00001165295	5534745	5535050
ENSE00001677690	5563162	5563211
ENSE00001801096	5522533	5522601
ENSE00001919793	5569954	5571282
ENSE00001955103	5510531	5510803

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 84.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3102 / max 308.0017, expressed in 1158 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95952	10.3920	1133
95954	0.6241	285
95953	0.6169	307
95956	0.4885	241
95955	0.1886	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	84.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.48	gold quality
calcaneal tendon	UBERON:0003701	79.36	gold quality
vermiform appendix	UBERON:0001154	77.40	gold quality
lymph node	UBERON:0000029	74.83	gold quality
spleen	UBERON:0002106	73.91	gold quality
gall bladder	UBERON:0002110	72.04	gold quality
smooth muscle tissue	UBERON:0001135	71.90	gold quality
caecum	UBERON:0001153	70.46	gold quality
upper lobe of left lung	UBERON:0008952	70.14	gold quality
omental fat pad	UBERON:0010414	69.50	gold quality
peritoneum	UBERON:0002358	69.42	gold quality
right lung	UBERON:0002167	68.54	gold quality
adipose tissue of abdominal region	UBERON:0007808	67.92	gold quality
right coronary artery	UBERON:0001625	67.85	gold quality
upper lobe of lung	UBERON:0008948	67.75	gold quality
subcutaneous adipose tissue	UBERON:0002190	67.69	gold quality
rectum	UBERON:0001052	67.51	gold quality
ascending aorta	UBERON:0001496	66.93	gold quality
right atrium auricular region	UBERON:0006631	66.89	gold quality
thoracic aorta	UBERON:0001515	66.87	gold quality
apex of heart	UBERON:0002098	66.50	gold quality
cardiac atrium	UBERON:0002081	66.41	gold quality
endocervix	UBERON:0000458	66.21	gold quality
descending thoracic aorta	UBERON:0002345	65.96	gold quality
tendon	UBERON:0000043	65.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	65.74	gold quality
muscle of leg	UBERON:0001383	65.52	gold quality
left uterine tube	UBERON:0001303	65.38	gold quality
left coronary artery	UBERON:0001626	65.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU2F2, STAT6

miRNA regulators (miRDB)

88 targeting PDCD1LG2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-6885-3P	99.75	70.36	3187

Literature-anchored findings (GeneRIF, showing 40)

• Blockade of PD-L2 during T cell responses initiated by allogenic dendritic cells increases T cell proliferation and cytokine production, showing that PD-L2 functions to inhibit T cell activation. (PMID:12538684)
• Binding properties of B7-DC to programmed death-1. (PMID:12893276)
• regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. (PMID:14515261)
• Administration of anti-PD-L2 mAb did not significantly affect the prolongation of graft survival. (PMID:14724428)
• Two novel splice variants of PD-L2 were cloned and identified. (PMID:15253154)
• Data suggest that PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer. (PMID:15837746)
• Via its interaction with programmed death-1 (PD-1) on human T cells, PD-L2 acts only as a negative regulator of T cell activity, inhibiting proliferation, IL-2 production, and IFN-gamma production. (PMID:16278812)
• PD-L2 negatively regulates human T cell activation and thus might be a candidate molecule for immunotherapeutic approaches aimed to attenuate pathological immune responses. (PMID:16598819)
• data do not support an association between systemic lupus erythematosus and SNP’s within the genes of the PDCD1 ligands PD-L1 and PD-L2 (PMID:17136123)
• Modulation of PD-L2 system may play a role in the development of autoimmune liver diseases. (PMID:17311651)
• PD-L2 47103 T may be associated with susceptibility to SLE in Taiwan (PMID:17343323)
• Polymorphisms of PD-L2 are not associated with susceptibility to rheumatoid arthritis in Taiwan. (PMID:17597384)
• deficient cellular immunity observed in Hodgkin lymphoma patients can be explained by “T-cell exhaustion,” which is led by the activation of PD-1-PD-L signaling pathway (PMID:18203952)
• HRV-16 infection or exposure to dsRNA induces epithelial B7-H1 and B7-DC (PMID:18378285)
• Programmed death 1 is a marker of angioimmunoblastic T-cell lymphoma and B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia. (PMID:18479731)
• PD-1 has a key regulatory role during the immune response of the host to the pathogen (PMID:18566376)
• Isolated decidual stromal cells constitutively express B7DC and B7H1; B7DC and B7H1 expression can be up-regulated (by IFN-gamma or TNF-alpha); B7DC and B7H1 appear to function in cell-to-cell communication. (PMID:19729380)
• All forms of chronic necroinflammatory liver disease examined correlate with increased B7-H1 and B7-DC expression on Kupffer cells, liver sinusoidal epithelial cells, and leukocytes. (PMID:19739236)
• Findings demonstrate that the pretreatment of tumor cells with IFN-gamma enhances B7-DC expression through ERK and JNK pathways. (PMID:20390427)
• the PD-1 pathway is active in immature Langerhans cells and inhibits iLC activities, but expression of receptor and ligands reverses upon maturation and PD-L1 and PD-L2 on mLC function to inhibit T-cell responses (PMID:20445553)
• PD-L1 and PD-L2 bound PD-1 with comparable affinities, but striking differences were observed at the level of the association and dissociation characteristics (PMID:20587542)
• Results suggest that over-expression of PD-1, PD-L1 and PD-L2 within liver may participate in local immune dysfunction, which could be one of the mechanisms involved in the chronicity of HBV infection and chronic inflammation seen in CHB patients. (PMID:20661763)
• PD-L1 and PD-L2 knockdown dendritic cells showed superior potential to expand minor histocompatibility antigen-specific CD8(+) effector and memory T cells from leukemia patients early after donor lymphocyte infusion and later during relapse. (PMID:20682852)
• Transgenic PD-L2 affects transition to memory when expressed on antigen (Ag)-presenting cells at the beginning of interaction with T cells; notably, interaction with PD-1 on T cells is required during the initial encounter with Ag. (PMID:20709947)
• REVIEW: role of PD-L1 and PD-L2 and ligands in allergic disease and asthma. (PMID:20722638)
• increased expression of PD-L2, as a costimulatory molecule, may have an important modulatory function on the local immune responses of OLP in vivo. (PMID:21457347)
• These observations indicate that PD-L2 is expressed following activation and is involved in the regulation of T cell function (PMID:21752471)
• Our results suggest that PD-1 G-536A, PD-L1 A8923C and PD-L2 C47103T polymorphisms are associated with the presence of ankylosing spondylitis. (PMID:21791547)
• Data suggest that PD-L1 may contribute to negative regulation of the immune response in chronic hepatitis B, and that PD-1 and PD-L1 and 2 may play a role in immune evasion of tumors. (PMID:21876620)
• Data suggest that brain endothelial cells contribute to control T cell transmigration into the CNS and immune responses via PD-L2 but not PD-L1 expression. (PMID:22067141)
• Data show that PD-1, PD-L1, PD-L2, CCL17, and CCL22 mRNA was identified in papillomas. (PMID:22322668)
• expression of PD-1 and its ligands, PD-L1 and PD-L2, in liver biopsies from HBV-related acute-on-chronic liver failure (HBV-ACLF) and chronic hepatitis B (CHB) patients were analyzed; results showed all 3 molecules were observed in the HBV-ACLF samples and levels were significantly higher than in CHB (PMID:22895698)
• PD-L1 and PD-L2 expressed on hPMSCs could inhibit the hPMSCs-mediated up-regulation on the expression of IL-17 secreted by peripheral blood T cells (PMID:23388330)
• Macrophages from infected animals show increased expression of PDL2 and CD80 that was dependent from the sex of the host. (PMID:23533995)
• High Expression of PD-L2 is associated with myelodysplastic syndromes. (PMID:24270737)
• PD-1/PD-Ls pathways on PMCs inhibited proliferation and adhesion activity of CD4+ T cells, suggesting that Mycobacterium tuberculosis might exploit PD-1/PD-Ls pathways to evade host cell immune response in human. (PMID:24406080)
• Recurrent genomic rearrangement events in CD274 and PDCD1LG2 underlie an immune privilege phenotype in a subset of B-cell lymphomas. (PMID:24497532)
• Data indicate that the bone morphogenetic proteins (BMPs) signaling pathway regulates PD-L1 and PD-L2 expression in monocyte-derived dendritic cells (MoDCs) during the maturation process. (PMID:24532425)
• conclude that PD-L2 protein is robustly expressed by the majority of primary mediastinal (thymic) large B-cell lymphomas (PMID:25025450)
• Results show that human-derived chordoma cell lines demonstrate inducible expression of PD-L1 and PD-L2, and that primary chordoma tissue shows variable expression of PD-1 and PD-L1 in infiltrating immune cells (PMID:25349132)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-241b2.5	ENSDARG00000100899
mus_musculus	Pdcd1lg2	ENSMUSG00000016498
rattus_norvegicus	Pdcd1lg2	ENSRNOG00000016136

Paralogs (12): CD86 (ENSG00000114013), CD274 (ENSG00000120217), CD80 (ENSG00000121594), RFPL1 (ENSG00000128250), RFPL2 (ENSG00000128253), RFPL3 (ENSG00000128276), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), RFPL4A (ENSG00000223638), RFPL4AL1 (ENSG00000229292), RFPL4B (ENSG00000251258)

Protein

Protein identifiers

Programmed cell death 1 ligand 2 — Q9BQ51 (reviewed: Q9BQ51)

Alternative names: Butyrophilin B7-DC

All UniProt accessions (1): Q9BQ51

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in induction and maintenance of immune tolerance to self. Acts as a ligand for the inhibitory receptor PDCD1/PD-1, inhibiting T-cell proliferation by blocking cell cycle progression and cytokine production.

Subcellular location. Secreted Endomembrane system Cell membrane.

Tissue specificity. Highly expressed in heart, placenta, pancreas, lung and liver and weakly expressed in spleen, lymph nodes and thymus.

Induction. Up-regulated by IFNG/IFN-gamma stimulation in monocytes and induced on dendritic cells grown from peripheral blood mononuclear cells with CSF2 and IL4/interleukin-4.

Similarity. Belongs to the immunoglobulin superfamily. BTN/MOG family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BQ51-1	1, PD-L2I, Type I	yes
Q9BQ51-2	2, PD-L2II, Type II
Q9BQ51-3	3, PD-L2III, Type III

RefSeq proteins (1): NP_079515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051713	T-cell_Activation_Regulation	Family
IPR053896	BTN3A2-like_Ig-C	Domain

Pfam: PF22705

UniProt features (30 total): strand 7, glycosylation site 5, splice variant 3, sequence variant 3, helix 3, disulfide bond 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6UMT	X-RAY DIFFRACTION	1.99
8J3V	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ51-F1	86.27	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 42–102, 143–192

Glycosylation sites (5): 163, 189, 37, 64, 157

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-389948	Co-inhibition by PD-1
R-HSA-9931295	PD-L1(CD274) glycosylation and translocation to plasma membrane

MSigDB gene sets: 251 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_LYMPHOCYTE_COSTIMULATION, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (13): adaptive immune response (GO:0002250), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), T cell costimulation (GO:0031295), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-10 production (GO:0032693), positive regulation of T cell proliferation (GO:0042102), negative regulation of T cell proliferation (GO:0042130), negative regulation of activated T cell proliferation (GO:0046007), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), cellular response to lipopolysaccharide (GO:0071222), immune system process (GO:0002376)

GO Molecular Function (2): receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of T cell activation by CD28 family	1
Regulation of PD-L1(CD274) Post-translational modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
positive regulation of T cell activation	2
negative regulation of cytokine production	2
T cell proliferation	2
regulation of T cell proliferation	2
plasma membrane	2
immune response	1
immune system process	1
response to stimulus	1
lymphocyte costimulation	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
positive regulation of lymphocyte proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
negative regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
biological_process	1
signaling receptor binding	1
signaling receptor activator activity	1
binding	1
membrane	1
cell periphery	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

2154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDCD1LG2	PDCD1	Q15116	999
PDCD1LG2	CTLA4	P16410	999
PDCD1LG2	CD80	P33681	993
PDCD1LG2	CD28	P10747	975
PDCD1LG2	RGMB	Q6NW40	974
PDCD1LG2	ICOS	Q9Y6W8	971
PDCD1LG2	CD86	P42081	970
PDCD1LG2	CD274	Q9NZQ7	970
PDCD1LG2	VTCN1	Q7Z7D3	935
PDCD1LG2	HAVCR2	Q8TDQ0	925
PDCD1LG2	CD8A	P01732	904
PDCD1LG2	CD4	P01730	896
PDCD1LG2	LAG3	P18627	870
PDCD1LG2	TIGIT	Q495A1	859
PDCD1LG2	IFNG	P01579	826

IntAct

99 interactions, top by confidence:

A	B	Type	Score
CD274	PDCD1	psi-mi:“MI:0915”(physical association)	0.890
PDCD1LG2	PDCD1	psi-mi:“MI:0407”(direct interaction)	0.850
PDCD1	PDCD1LG2	psi-mi:“MI:0407”(direct interaction)	0.850
PDCD1	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.850
CD274	PDCD1LG2	psi-mi:“MI:0914”(association)	0.740
TSSK6	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
CD274	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.740
PDCD1LG2	CD274	psi-mi:“MI:0407”(direct interaction)	0.740
SLC7A1	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.560
GPR37L1	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.560
TMEM97	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.560
RUSF1	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.560
PDCD1LG2	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
GALNT15	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): PDCD1LG2 (Reconstituted Complex), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid), PDCD1LG2 (Two-hybrid)

ESM2 similar proteins: A0A1B0GW64, A4FUY1, A5D7B2, A6QQ85, A8MVS5, B0FP48, E5RIL1, O18796, O19131, O75022, O75023, P09564, P0C191, P15151, P19438, P24071, P31994, P31995, P32506, P32942, P38484, P49772, P50555, Q01113, Q13477, Q14CZ8, Q28110, Q5DRQ8, Q61190, Q640R3, Q6AZ51, Q6BAA4, Q6GTX8, Q6PGD0, Q6UW56, Q6UX52, Q75VT8, Q7Z692, Q863H2, Q86YD3

Diamond homologs: Q9BQ51, Q9EP73, Q9NZQ7, Q9WUL5, P13591, P31836, Q501W4, Q7TSP5, Q96RW7, Q2EY15, Q2VWP7, Q2VWP9, Q589G5, Q5R7W8, Q8WVV5, Q7TPB4, Q8VE98

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — MEL, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
815186	GRCh37/hg19 9p24.3-22.2(chr9:203861-17789410)x1	Pathogenic

SpliceAI

947 predictions. Top by Δscore:

Variant	Effect	Δscore
9:5563207:GTGCT:G	donor_gain	1.0000
9:5563209:GCT:G	donor_gain	1.0000
9:5563212:G:GG	donor_gain	1.0000
9:5563216:G:GG	donor_gain	1.0000
9:5534741:TCA:T	acceptor_loss	0.9900
9:5534743:A:AG	acceptor_gain	0.9900
9:5534743:AGCT:A	acceptor_loss	0.9900
9:5534744:G:GG	acceptor_gain	0.9900
9:5534744:GC:G	acceptor_gain	0.9900
9:5534744:GCT:G	acceptor_gain	0.9900
9:5534744:GCTT:G	acceptor_gain	0.9900
9:5534744:GCTTT:G	acceptor_gain	0.9900
9:5549605:G:GG	donor_gain	0.9900
9:5563197:G:T	donor_gain	0.9900
9:5563208:TGCT:T	donor_gain	0.9900
9:5563209:GCTG:G	donor_gain	0.9900
9:5563214:GA:G	donor_gain	0.9900
9:5534740:TTCA:T	acceptor_gain	0.9800
9:5534741:TCAG:T	acceptor_gain	0.9800
9:5534742:CAGCT:C	acceptor_gain	0.9800
9:5534743:A:T	acceptor_gain	0.9800
9:5534744:G:T	acceptor_gain	0.9800
9:5563156:TTTCA:T	acceptor_loss	0.9800
9:5563157:TTCA:T	acceptor_loss	0.9800
9:5563158:TCAGA:T	acceptor_loss	0.9800
9:5563159:CAGA:C	acceptor_loss	0.9800
9:5563160:A:AG	acceptor_gain	0.9800
9:5563160:A:T	acceptor_loss	0.9800
9:5563161:G:GG	acceptor_gain	0.9800
9:5567955:T:G	acceptor_gain	0.9800

AlphaMissense

1791 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:5549438:G:C	W155C	0.996
9:5549438:G:T	W155C	0.996
9:5549406:G:C	A145P	0.992
9:5549505:A:C	S178R	0.991
9:5549507:T:A	S178R	0.991
9:5549507:T:G	S178R	0.991
9:5534993:T:A	C102S	0.990
9:5534994:G:C	C102S	0.990
9:5549400:T:A	C143S	0.990
9:5549401:G:C	C143S	0.990
9:5549436:T:A	W155R	0.990
9:5549436:T:C	W155R	0.990
9:5534987:T:G	Y100D	0.988
9:5534993:T:C	C102R	0.988
9:5549400:T:C	C143R	0.988
9:5549547:T:A	C192S	0.985
9:5549548:G:C	C192S	0.985
9:5534813:T:A	C42S	0.984
9:5534814:G:C	C42S	0.984
9:5549402:C:G	C143W	0.983
9:5534988:A:C	Y100S	0.981
9:5534988:A:G	Y100C	0.981
9:5549401:G:A	C143Y	0.981
9:5549395:T:C	L141P	0.980
9:5549412:G:T	G147C	0.980
9:5534995:C:G	C102W	0.979
9:5549554:T:G	F194C	0.978
9:5549553:T:C	F194L	0.977
9:5549555:C:A	F194L	0.977
9:5549555:C:G	F194L	0.977

dbSNP variants (sampled 300 via entrez): RS1000024518 (9:5535265 T>C), RS1000138780 (9:5555285 C>T), RS1000141317 (9:5529829 T>C), RS1000157661 (9:5551058 G>A), RS1000178001 (9:5551427 A>G), RS1000278449 (9:5509330 G>A,T), RS1000282307 (9:5543252 C>T), RS1000390038 (9:5510543 C>T), RS1000414609 (9:5510335 A>G), RS1000454313 (9:5515847 C>T), RS1000513021 (9:5561565 G>A), RS1000566396 (9:5544612 G>A), RS1000569535 (9:5525876 G>A,C), RS1000619132 (9:5531125 C>G,T), RS1000633029 (9:5543371 C>G)

Disease associations

OMIM: gene MIM:605723 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_1590	Blood protein levels	3.000000e-70
GCST011353_52	Serum alkaline phosphatase levels	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3713006 (SINGLE PROTEIN), CHEMBL5482985 (PROTEIN COMPLEX), CHEMBL6066575 (PROTEIN FAMILY)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7870226	PDCD1LG2		0.00	0

ChEMBL bioactivities

434 potent at pChembl≥5 of 436 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.39	EC50	0.41	nM	CHEMBL4635204
9.14	EC50	0.72	nM	CHEMBL4635204
7.40	EC50	40	nM	CHEMBL4438020
7.19	IC50	64	nM	CHEMBL6018891
7.19	IC50	64	nM	CHEMBL5950648
7.19	IC50	64	nM	CHEMBL5889285
7.19	IC50	64	nM	CHEMBL5829298
7.19	IC50	64	nM	CHEMBL5956967
7.19	IC50	64	nM	CHEMBL5968911
7.19	IC50	64	nM	CHEMBL5947668
7.19	IC50	64	nM	CHEMBL5953024
7.19	IC50	64	nM	CHEMBL5924251
7.19	IC50	64	nM	CHEMBL6031354
7.19	IC50	64	nM	CHEMBL5846484
7.19	IC50	64	nM	CHEMBL5924911
7.19	IC50	65	nM	CHEMBL5764455
7.19	IC50	64	nM	CHEMBL5996759
7.19	IC50	64	nM	CHEMBL5764024
7.19	IC50	64	nM	CHEMBL5811746
7.19	IC50	64	nM	CHEMBL5935121
7.19	IC50	64	nM	CHEMBL6044853
7.19	IC50	64	nM	CHEMBL5766454
7.17	IC50	67	nM	CHEMBL5914761
7.17	IC50	67	nM	CHEMBL5940820
7.16	IC50	70	nM	CHEMBL5768423
7.15	IC50	71	nM	CHEMBL5831453
7.13	IC50	74	nM	CHEMBL5870436
7.12	IC50	75	nM	CHEMBL6033898
7.10	IC50	79	nM	CHEMBL5982486
7.08	IC50	84	nM	CHEMBL5855511
7.07	IC50	86	nM	CHEMBL5792514
7.06	IC50	88	nM	CHEMBL5845950
7.06	IC50	87	nM	CHEMBL5989451
7.05	IC50	90	nM	CHEMBL5928627
7.04	IC50	92	nM	CHEMBL5908504
7.04	IC50	91	nM	CHEMBL6036765
7.03	IC50	94	nM	CHEMBL5937892
7.03	IC50	93	nM	CHEMBL6045465
7.02	IC50	95	nM	CHEMBL5790897
7.00	IC50	100	nM	CHEMBL5946916
6.97	IC50	108	nM	CHEMBL5806559
6.97	IC50	107	nM	CHEMBL5854445
6.97	IC50	107	nM	CHEMBL6026822
6.97	IC50	108	nM	CHEMBL5779245
6.96	IC50	111	nM	CHEMBL5883026
6.96	IC50	109	nM	CHEMBL6055965
6.96	IC50	110	nM	CHEMBL5918416
6.94	IC50	115	nM	CHEMBL5770862
6.93	IC50	118	nM	CHEMBL5815984
6.93	IC50	118	nM	CHEMBL5758410

PubChem BioAssay actives

4 with measured affinity, of 5 total; 3 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
(4S)-5-amino-4-[[(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2,6-bis[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	2017896: Inhibition of PD-I/PD-L2 interaction (unknown origin) expressed in human MDA-MB-23 cells	ec50	0.0004	uM
(2S,3R)-2-[[(2S)-4-amino-1-[2-[(2S)-2-amino-3-hydroxypropanoyl]hydrazinyl]-1,4-dioxobutan-2-yl]carbamoylamino]-3-hydroxybutanoic acid	1652979: Inhibition of PDL2 (unknown origin)	ec50	0.0400	uM
(2S)-2-[[(1S)-3-amino-1-[5-[(1S)-1-amino-2-hydroxyethyl]-1,3,4-thiadiazol-2-yl]-3-oxopropyl]carbamoylamino]-3-hydroxybutanoic acid	1930240: Inhibition of PD-L2 in human PBMCs assessed as increase in INFgamma production	ec50	0.1490	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
TL8-506	affects cotreatment, increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	affects expression	1
dimethylarsinous acid	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1
incobotulinumtoxinA	decreases expression	1
gardiquimod	increases expression, decreases reaction	1
Aripiprazole	affects cotreatment, increases expression	1
Oxaliplatin	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Cisplatin	increases expression, decreases expression, affects cotreatment, decreases reaction	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Fluorouracil	affects reaction, decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases reaction, increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ozone	affects cotreatment, increases expression	1
Smoke	increases expression	1
Tretinoin	increases expression	1
Carboplatin	decreases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4613352	Binding	Inhibition of PDL2 (unknown origin)	Peptide-based and small synthetic molecule inhibitors on PD-1/PD-L1 pathway: A new choice for immunotherapy? — Eur J Med Chem

Cellosaurus cell lines

11 cell lines: 7 cancer cell line, 3 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2PG	Abcam A-549 PDCD1LG2 KO	Cancer cell line	Male
CVCL_B7YN	Abcam Raji PDCD1LG2 KO	Cancer cell line	Male
CVCL_B9ZD	Abcam THP-1 PDCD1LG2 KO	Cancer cell line	Male
CVCL_C7B2	Abcam PC-3 PDCD1LG2 KO	Cancer cell line	Male
CVCL_D7BT	Abeomics CHO-K1 PD-L2	Spontaneously immortalized cell line	Female
CVCL_D7J1	Ubigene 786-O PDCD1LG2 KO	Cancer cell line	Male
CVCL_E5IA	CHO-K1/PD-L2	Spontaneously immortalized cell line	Female
CVCL_E6RH	Genomeditech CHO-K1 H_PDCD1LG2(PDL2)	Spontaneously immortalized cell line	Female
CVCL_TC59	HAP1 PDCD1LG2 (-) 1	Cancer cell line	Male
CVCL_UE48	293T human PDL2	Transformed cell line	Female

Clinical trials (associated diseases)

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