GeneBe

CD70

protein-coding

CD70 molecule, the group of CD molecules|Tumor necrosis factor superfamily

Gene summary

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for TNFRSF27/CD27. It is a surface antigen on activated, but not on resting, T and B lymphocytes. It induces proliferation of costimulated T cells, enhances the generation of cytolytic T cells, and contributes to T cell activation. This cytokine is also reported to play a role in regulating B-cell activation, cytotoxic function of natural killer cells, and immunoglobulin sythesis. [provided by RefSeq, Jul 2008]

Previous symbols:
  • CD27LG
  • TNFSF7

MANE transcript

NM_001252.5

Inheritance

AR

ClinVar variants

P:2U:34B:8

Top phenotype

Lymphoproliferative syndrome 3

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr19:6,583,183-6,604,103

External References & Databases

Ensembl (ENSG00000125726)NCBI Gene (970)OMIM (602840)HGNC:11937GenCCUniProt (P32970)AlphaFoldClinVar (CD70)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~20.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

severe combined immunodeficiency due to CD70 deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0034054

Submitter: Ambry Genetics

severe combined immunodeficiency due to CD70 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0034054

Submitter: Labcorp Genetics (formerly Invitae)

severe combined immunodeficiency due to CD70 deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0034054

Submitter: ClinGen

CD70 was first reported in relation to AR immundeficiency and succeptibiltiy to EBV infection and related malignancy in 2017(Iwaza et al., PMID: 28011863). Additional symptoms reporte din humans include Bechet's like syndromes and periodic fever. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism(s) or inheritance pattern. Therefore, the following disease entities have been lumped into one disease entities, (OMIM: 28011863) Multiple variants (missense, frameshift) have been reported in 5 probands in 4 publications (PMIDs: 28011863, 28011864, 29434583, 32849540) are included in this curation. Significant functional testing was done. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is reported to be loss of function of CD70. This gene-disease relationship is also supported by animal models, expression studies, in vitro functional assays, etc.) (PMIDs: 23269247, 28011863, 28011864, 29434583, 32849540). In summary, there is definitive evidence supporting the relationship between CD70 and AR lymphoproliferaiton with immunodeficiency 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 PIRD GCEP on the meeting date 5/21/24.

Clinical Genomic Database (CGD)

Lymphoproliferative syndrome 3AR

Manifestation: Allergy/Immunology/Infectious; Oncologic

Intervention: Allergy/Immunology/Infectious; Oncologic

Rationale: Some individuals may patients may have recurrent infections, and awareness may allow prophylactic measures and prompt and aggressive management of infections; Individuals have been described as having increased susceptibility to Epstein-Barr virus infection, causing increased risk of B-cell malignancies, and awareness may allow prompt diagnosis and management of oncologic disease

Refs: 28011863; 28011864Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD70 variants in ClinVar

5 Conditions Cataloged
Inborn genetic diseasesTotal: 25
not providedTotal: 14
not specifiedTotal: 10
CD70-related disorderTotal: 4
Severe combined immunodeficiency due to CD70 deficiencyTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001252.5. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
5
clinvar
 6
missense
31
clinvar
3
clinvar
 34
nonsense
1
clinvar
 1
start loss
0
frameshift
1
clinvar
1
clinvar
 2
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total20348044

Highest pathogenic variant AF is 0.0000027365022

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001252.5RefSeqNP_001243.13MANE Select
ENST00000245903.4EnsemblENSP00000245903.23MANE Select
NM_001330332.2RefSeqNP_001317261.14Standard
ENST00000423145.7EnsemblENSP00000395294.24Standard

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

  • immune response
  • signal transduction
  • cell-cell signaling
  • cell population proliferation
  • regulation of signaling receptor activity

Molecular Function

  • protease binding
  • signaling receptor binding
  • cytokine activity
  • tumor necrosis factor receptor binding
  • protein binding

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000245903
Coding exons
3
Length
20921
Individuals with no LoFs
125736
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125738
p
0.00000795
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.802971220.7960.000007141211
Missense (PolyPhen)2344.1870.52052366
Synonymous0.6694753.20.8830.00000274443
Loss of Function0.38333.810.7881.63e-741

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Cytokine that binds to CD27. Plays a role in T-cell activation. Induces the proliferation of costimulated T-cells and enhances the generation of cytolytic T-cells.;

Recessive Scores

pRec
0.215

Intolerance Scores

LoFtool
0.259
RVIS EVS
-0.43
RVIS percentile EVS
25.15

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.184

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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