CD27
protein-codingCD27 molecule, the group of CD molecules|Tumor necrosis factor receptor superfamily
Gene summary
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]
- TNFRSF7
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014054
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014054
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0016536
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014054
Submitter: ClinGen
*CD27* was first reported in relation to autosomal recessive *CD27*-related lymphoproliferative and immune disorder in 1998 (Schmitter et al., PMID: 10444164). *CD27* is a member of the TNF receptor superfamily. It is required for regeneration and long term maintenance of T-cell immunity. It binds with CD70 ligand and serves a key role in regulating survival, function, and differentiation of T, B, NK and plasma cells. *CD27*-related lymphoproliferative and immune disorder is described as having disease onset within the first few months or years of life. This condition has a highly variable phenotype which can range from asymptomatic, to borderline hypogammaglobulinemia, to fully symptomatic with life-threatening EBV-related complications, as well as hematologic malignancies. Two null variants and five missense variants reported in 12 individuals in 5 publications (PMIDs: 22197273, 22801960, 25843314, 32041749, 28011863) are included in this curation. These variants are supportive of the gene-disease relationship with case-level data, segregation data, and functional data. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by animal models and expression studies (PMIDs: 11062504, 10444164, 33827115). In summary, there is definitive evidence supporting the relationship between *CD27* and autosomal recessive lymphoproliferative and immune disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Childhood, Adolescent, and Young Adult Cancer Predisposition GCEP on the meeting date December 9th, 2025 (SOP Version 11).
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Hematologic; Oncologic
Intervention: Allergy/Immunology/Infectious; Hematologic; Oncologic
Rationale: The condition can involve childhood-onset immunodeficiency, and prophylactic measures, treatment, and prompt and aggressive treatment of infections may be beneficial; Individuals may manifest with hemophagocytic lymphohistiocytosis syndrome , and awareness can allow efficient management, but stem cell transplant may be indicated in such instances; Additional malignancies have been described, and awareness may allow recognition and treatment; HSCT has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CD27 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001242.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 57 | 1 | 59 | ||
| missense | 1 | 1 | 113 | 4 | 119 | |
| nonsense | 3 | 2 | 5 | |||
| start loss | 1 | 1 | ||||
| frameshift | 6 | 4 | 1 | 11 | ||
| splice donor/acceptor (+/-2bp) | 4 | 1 | 5 | |||
| Total | 10 | 11 | 117 | 61 | 1 | 200 |
Highest pathogenic variant AF is 0.000042142266
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001233.2 | 6 | MANE Select | |
| Ensembl | ENSP00000266557.3 | 6 | MANE Select | |
| RefSeq | NP_001400192.1 | 7 | Standard | |
| RefSeq | NP_001400193.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- TNFR2 non-canonical NF-kB pathway
- Cytokine Signaling in Immune system
- Immune System
- TNFs bind their physiological receptors
Biological Process
- cell surface receptor signaling pathway
- immunoglobulin mediated immune response
- tumor necrosis factor-mediated signaling pathway
- negative regulation of apoptotic process
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Molecular Function
- transmembrane signaling receptor activity
- protein binding
- cysteine-type endopeptidase inhibitor activity involved in apoptotic process
Cellular Component
- extracellular region
- plasma membrane
- integral component of plasma membrane
- external side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000266557
- Coding exons
- 6
- Length
- 6852
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.132 | 148 | 153 | 0.970 | 0.00000841 | 1679 |
| Missense (PolyPhen) | 32 | 38.397 | 0.83341 | 445 | ||
| Synonymous | 0.252 | 56 | 58.4 | 0.958 | 0.00000323 | 514 |
| Loss of Function | 1.76 | 5 | 11.4 | 0.437 | 5.85e-7 | 122 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for CD70/CD27L. May play a role in survival of activated T-cells. May play a role in apoptosis through association with SIVA1.;
- Disease
- DISEASE: Lymphoproliferative syndrome 2 (LPFS2) [MIM:615122]: An autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impaired T-cell-dependent B-cell responses and T-cell dysfunction. The phenotype is highly variable, ranging from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation. {ECO:0000269|PubMed:22197273, ECO:0000269|PubMed:22801960}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.432
Intolerance Scores
- LoFtool
- 0.361
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.743
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |