PDCD1

Chr 2AR

programmed cell death 1

Also known as: ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2, hPD-1, hPD-l

NCBI Gene: 5133 ENSG00000188389 UniProt: Q15116 OMIM: 600244

Programmed cell death protein 1 (PDCD1) is an immune-inhibitory receptor expressed in activated T cells; it is involved in the regulation of T-cell functions, including those of effector CD8+ T cells. In addition, this protein can also promote the differentiation of CD4+ T cells into T regulatory cells. PDCD1 is expressed in many types of tumors including melanomas, and has demonstrated to play a role in anti-tumor immunity. Moreover, this protein has been shown to be involved in safeguarding against autoimmunity, however, it can also contribute to the inhibition of effective anti-tumor and anti-microbial immunity. [provided by RefSeq, Aug 2020]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Autoimmune disease, multisystem, infantile-onset, 4MIM #621004

Clinical highlights

Gene–disease validity (ClinGen)

Limited · autoimmune disease · AR · ClinGen 2025

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

291

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.417

Z-score 2.26

OE 0.21 (0.09–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.29Z-score

OE missense 0.74 (0.64–0.85)

139 obs / 189.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.09–0.66)

0≤0.351.4

Missense OE?0.74 (0.64–0.85)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 2 / 9.5Missense obs/exp: 139 / 189.1Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in PDCD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

333 rare PASS variants

Rare truncating (LoF)

1 in 3,800

28 rare PASS variants

Rare synonymous (reference)

1 in 130

176 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDCD1. 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 250	1 in 8,900
South Asian	~43k	1 in 210	1 in 5,300
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 15,000
European (Finnish)	~27k	1 in 720	1 in 1,200
Admixed American	~22k	1 in 170	≈ 1 in 7,600
African / African American	~21k	1 in 120	1 in 1,800
East Asian	~20k	1 in 230	none seen
Ashkenazi Jewish	~13k	1 in 410	none seen
Middle Eastern	~2,884	1 in 150	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.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓