CD27

Chr 12AR

CD27 molecule

Also known as: S152, S152. LPFS2, T14, TNFRSF7, Tp55

NCBI Gene: 939 ENSG00000139193 UniProt: P26842 OMIM: 186711

CD27 encodes a costimulatory immune-checkpoint receptor on T-cells, NK-cells and B-cells that binds CD70 to mediate antigen-specific T-cell activation and expansion, providing immune surveillance of B-cells. Mutations cause lymphoproliferative syndrome 2, an autosomal recessive primary immunodeficiency characterized by abnormal lymphocyte proliferation and immune dysregulation. The gene shows low constraint to loss-of-function variants (pLI 0.01, LOEUF 0.92), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. This receptor transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 have been shown to mediate the signaling process of this receptor. CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lymphoproliferative syndrome 2MIM #615122

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · lymphoproliferative syndrome 2 · AR · ClinGen 2025

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.92

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CD27

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.010

Z-score 1.76

OE 0.44 (0.23–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.97 (0.85–1.11)

148 obs / 152.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.23–0.92)

0≤0.351.4

Missense OE?0.97 (0.85–1.11)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 5 / 11.4Missense obs/exp: 148 / 152.6Syn Z: 0.25

Background carrier burden — how many people carry a rare variant somewhere in CD27?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

323 rare PASS variants

Rare truncating (LoF)

1 in 3,600

54 rare PASS variants

Rare synonymous (reference)

1 in 260

145 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD27. 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 280	1 in 3,600
South Asian	~43k	1 in 200	1 in 5,400
Remaining (unassigned)	~30k	1 in 200	≈ 1 in 15,000
European (Finnish)	~27k	1 in 850	≈ 1 in 27,000
Admixed American	~22k	1 in 160	none seen
African / African American	~21k	1 in 140	1 in 1,800
East Asian	~20k	1 in 230	1 in 2,100
Ashkenazi Jewish	~13k	1 in 820	none seen
Middle Eastern	~2,884	1 in 170	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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓