CD274

Chr 9AR

CD274 molecule

Also known as: ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1, PDL1, hPD-L1

NCBI Gene: 29126 ENSG00000120217 UniProt: Q9NZQ7 OMIM: 605402

The protein is an immune inhibitory receptor ligand that regulates T-cell activation and maintains immune tolerance by limiting T-cell effector responses and preventing autoimmunity. Mutations cause autoimmune disease with multisystem involvement and infantile onset, inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Autoimmune disease, multisystem, infantile-onset, 5MIM #621235

Active trials

377

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.019

Z-score 2.08

OE 0.38 (0.20–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.90Z-score

OE missense 0.80 (0.69–0.93)

123 obs / 154.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.20–0.80)

0≤0.351.4

Missense OE?0.80 (0.69–0.93)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 5 / 13.1Missense obs/exp: 123 / 154.4Syn Z: -1.39

Background carrier burden — how many people carry a rare variant somewhere in CD274?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

367 rare PASS variants

Rare truncating (LoF)

1 in 7,900

32 rare PASS variants

Rare synonymous (reference)

1 in 180

166 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD274. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 11,000
South Asian	~43k	1 in 200	1 in 2,200
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 30,000
European (Finnish)	~27k	1 in 860	≈ 1 in 27,000
Admixed American	~22k	1 in 250	≈ 1 in 11,000
African / African American	~21k	1 in 160	1 in 3,600
East Asian	~20k	1 in 410	1 in 1,600
Ashkenazi Jewish	~13k	≈ 1 in 4,400	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 180	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.