PDCD1LG2

Chr 9

programmed cell death 1 ligand 2

Also known as: B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2, bA574F11.2

NCBI Gene: 80380 ENSG00000197646 UniProt: Q9BQ51 OMIM: 605723

The protein encoded by this gene acts as a ligand for the inhibitory receptor PD-1 and plays a critical role in maintaining immune tolerance by inhibiting T-cell proliferation and cytokine production. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF > 1), suggesting that complete loss of function is well-tolerated in humans. No Mendelian diseases have been definitively associated with pathogenic variants in this gene based on the available data.

OMIM ResearchSummary from RefSeq, UniProt

MultiplemechanismLOEUF 1.28

Clinical Summary— PDCD1LG2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.28LOEUF

pLI 0.000

Z-score 0.86

OE 0.73 (0.44–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-0.67Z-score

OE missense 1.16 (1.02–1.31)

168 obs / 145.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE0.73 (0.44–1.28)

0≤0.351.4

Missense OE1.16 (1.02–1.31)

0≤0.61.4

Synonymous OE1.13

0≤1.21.6

LoF obs/exp: 9 / 12.2Missense obs/exp: 168 / 145.4Syn Z: -0.79

0.77top 25%

GOF

0.74top 25%

LOF

0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PDCD1LG2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Malignant Neoplasm

KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J)

RECRUITING

NCT07252739Phase PHASE2Merck Sharp & Dohme LLCStarted 2025-12-19

MK-1084PembrolizumabCetuximab

Breast NeoplasmsTriple Negative Breast NeoplasmsHR Low-Positive/HER2-Negative Breast Neoplasms

A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)

RECRUITING

NCT06966700Phase PHASE3Merck Sharp & Dohme LLCStarted 2025-06-30

Sacituzumab tirumotecanPembrolizumabRescue Medication

Clinical Literature

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Landmark / reviewRecent case evidence

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