severe combined immunodeficiency due to CD70 deficiency

Summary

severe combined immunodeficiency due to CD70 deficiency (MONDO:0034054) is a disease caused by CD70 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CD70 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	severe combined immunodeficiency due to CD70 deficiency
Mondo ID	MONDO:0034054
OMIM	618261
Orphanet	538958
UMLS	C5568559
MedGen	1799982
GARD	0017978
Is cancer (heuristic)	no

Also known as: lymphoproliferative syndrome 3

Data availability: 3 ClinVar variants · 3 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › combined immunodeficiency › severe combined immunodeficiency › severe combined immunodeficiency due to CD70 deficiency

Related subtypes (10): recombinase activating gene 1 deficiency, recombinase activating gene 2 deficiency, janus kinase-3 deficiency, T-cell immunodeficiency, congenital alopecia, and nail dystrophy, T-B- severe combined immunodeficiency, severe combined immunodeficiency due to CARMIL2 deficiency, immunodeficiency 79, familial severe combined immunodeficiency, T-B+ severe combined immunodeficiency, T+ B+ severe combined immunodeficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
599337	NM_001252.5(CD70):c.535C>T (p.Arg179Ter)	CD70	Pathogenic	no assertion criteria provided
599338	NM_001252.5(CD70):c.250del (p.Ser84fs)	CD70	Pathogenic	no assertion criteria provided
599339	NM_001252.5(CD70):c.552CTT[1] (p.Phe186del)	CD70	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CD70	Definitive	Autosomal recessive	severe combined immunodeficiency due to CD70 deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD70	Orphanet:538958	EBV-induced lymphoproliferative disease due to CD70 deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CD70	HGNC:11937	ENSG00000125726	P32970	CD70 antigen	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD70	CD70 antigen	Expressed at the plasma membrane of B cells, it is the ligand of the CD27 receptor which is specifically expressed at the surface of T cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD70	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
cartilage tissue	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD70	154	broad	marker	cartilage tissue, buccal mucosa cell, triceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD70	1,808

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD70	P32970	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TNFs bind their physiological receptors	1	393.8×	0.010	CD70
TNFR2 non-canonical NF-kB pathway	1	181.3×	0.011	CD70
Cytokine Signaling in Immune system	1	40.8×	0.033	CD70
Immune System	1	13.0×	0.077	CD70

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
adaptive immune memory response involving T cells and B cells	1	5617.3×	1e-03	CD70
B cell mediated immunity	1	4213.0×	1e-03	CD70
CD27 signaling pathway	1	3370.4×	1e-03	CD70
T cell mediated immunity	1	991.3×	0.003	CD70
B cell proliferation	1	481.5×	0.004	CD70
T cell proliferation	1	383.0×	0.004	CD70
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.004	CD70
extrinsic apoptotic signaling pathway	1	306.4×	0.004	CD70
positive regulation of T cell proliferation	1	259.3×	0.004	CD70
T cell activation	1	259.3×	0.004	CD70

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD70	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CD70

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CD70	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.