CD70

Summary

CD70 (CD70 molecule, HGNC:11937) is a protein-coding gene on chromosome 19p13.3, encoding CD70 antigen (P32970). 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.

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.

Source: NCBI Gene 970 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe combined immunodeficiency due to CD70 deficiency (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 49 total — 3 pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• MANE Select transcript: NM_001252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11937
Approved symbol	CD70
Name	CD70 molecule
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CD27L, CD27-L
Ensembl gene	ENSG00000125726
Ensembl biotype	protein_coding
OMIM	602840
Entrez	970

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000245903, ENST00000423145, ENST00000597430, ENST00000894984

RefSeq mRNA: 2 — MANE Select: NM_001252 NM_001252, NM_001330332

CCDS: CCDS12170, CCDS82283

Canonical transcript exons

ENST00000245903 — 3 exons

Exon	Start	End
ENSE00001053508	6585839	6586405
ENSE00001159889	6590841	6591150
ENSE00003784659	6590103	6590136

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 80.25.

FANTOM5 (CAGE): breadth broad, TPM avg 22.7182 / max 1328.9145, expressed in 768 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178707	11.4673	527
178706	5.9934	379
178705	1.5826	160
178702	1.2323	317
178704	0.8945	111
178709	0.6931	245
178712	0.3536	184
178708	0.2445	167
178701	0.1594	107
178703	0.0975	64

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	80.25	gold quality
buccal mucosa cell	CL:0002336	79.10	silver quality
triceps brachii	UBERON:0001509	78.53	gold quality
gluteal muscle	UBERON:0002000	78.22	gold quality
tongue squamous epithelium	UBERON:0006919	77.48	gold quality
orbitofrontal cortex	UBERON:0004167	77.42	gold quality
Brodmann (1909) area 10	UBERON:0013541	76.61	silver quality
diaphragm	UBERON:0001103	76.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.45	gold quality
biceps brachii	UBERON:0001507	75.31	gold quality
endometrium epithelium	UBERON:0004811	74.77	gold quality
cerebellar vermis	UBERON:0004720	74.49	gold quality
mammary duct	UBERON:0001765	72.72	gold quality
frontal pole	UBERON:0002795	72.55	gold quality
paraflocculus	UBERON:0005351	72.28	silver quality
middle frontal gyrus	UBERON:0002702	71.84	gold quality
myocardium	UBERON:0002349	70.97	gold quality
epithelium of mammary gland	UBERON:0003244	70.76	gold quality
olfactory bulb	UBERON:0002264	70.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.28	gold quality
lymph node	UBERON:0000029	69.74	gold quality
Brodmann (1909) area 46	UBERON:0006483	69.68	gold quality
heart right ventricle	UBERON:0002080	69.53	gold quality
secondary oocyte	CL:0000655	69.46	gold quality
type B pancreatic cell	CL:0000169	69.45	gold quality
pancreatic ductal cell	CL:0002079	69.29	silver quality
vastus lateralis	UBERON:0001379	69.19	gold quality
quadriceps femoris	UBERON:0001377	69.17	gold quality
inferior olivary complex	UBERON:0002127	68.78	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	68.58	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	10.34
E-ANND-3	yes	3.42
E-MTAB-8060	no	75.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, FOXO1, MBD2, RFX1

miRNA regulators (miRDB)

7 targeting CD70, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-548AS-3P	99.12	69.12	2294

Literature-anchored findings (GeneRIF, showing 40)

• Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma (PMID:11980654)
• intragraft gene expression is not a risk factor for acute cardiac allograft rejection (PMID:12009595)
• Impaired up-regulation of CD70 and CD86 in naive B cells from patients with CVID suggests an intrinsic signalling or expression defect at the level of naive B cells in type I CVID. (PMID:12100033)
• IL-10 enhances B-cell IgE synthesis by promoting differentiation into plasma cells, a process that is inhibited by CD27/CD70 interaction (PMID:12197885)
• Systemic lupus erythematosus T cells and T cells treated with DNA methyltransferase inhibitors and ERK pathway inhibitors overexpress CD70. (PMID:15188362)
• Interaction of CD70 with CD27 plays a direct role in T cell activation mediated by IL-2. (PMID:16751420)
• Immunocytochemical analysis demonstrated that binding of an anti-CD70 antibody to CD70(TNFSF7), endogenously expressed on the surface of A498 and 786-O cell lines resulted in the rapid internalisation of the antibody-receptor complex. (PMID:16892042)
• Apoptosis mediated by exposure to the CD70 secreted by tumor cells may contribute to the failure of renal cell carcinoma patients to develop an effective lymphocyte-mediated antitumor response (PMID:17132225)
• CD27-CD70 interactions may promote Th1 cell formation by permitting naive T cells to respond to differentiation signals and by promoting survival of activated effector T cells. (PMID:17548342)
• reveal a novel role for non-Hodgkin lymphoma B cells in the development of intratumoral regulatory T cells (PMID:17615291)
• CD27-CD70 interactions in the pathogenesis of Waldenstrom macroglobulinemia. (PMID:18216294)
• CD70 gene was upregulated more than 1,000-fold and the enhanced expression of the CD70 molecule was confirmed by laser flow cytometry for various HTLV-1-carrying T-cell lines and primary CD4(+) T cells isolated from acute-type ATL patients. (PMID:18256142)
• Dendritic cells matured in the presence of PGE(2) induced the expression of OX40, OX40L, and CD70 on T cells facilitating T-cell/T-cell interaction that warrant long-lasting costimulation. (PMID:19029446)
• CD70 not only contributes to the activation of cytotoxic T cells in B cell precursor acute lymphoblastic leukemia but is a critical signal during the expansion phase of the cytotoxic T cell response. (PMID:19109206)
• Constitutive expression of CD70 transgene is sufficient to deregulate the CD8 T cell differentiation pathway of acute infection reminiscent of events in chronic infection. (PMID:19380782)
• Data showed that the CD70, perforin and KIR2DL4 promoters are demethylated in CD4(+)CD28(-) T cells, and that DNA methyltransferase 1 (Dnmt1) and Dnmt3a levels are decreased in this subset. (PMID:19394279)
• T(reg) cells in CLL may accumulate both by increased formation, facilitated by CD27-CD70 interaction in the lymph node proliferation centres, and decreased sensitivity to apoptosis because of a shifted Noxa-Bcl-2 balance (PMID:19452318)
• This is the first study which (i) extensively analyzes CD70 expression on human primary DC subsets and (ii) reveals that the CD70-CD27 interaction enhances not only Th1 but also Th2 differentiation of naive CD4+ T cells. (PMID:19556308)
• endogenous IL-18 might facilitate stomach cancer cell immune escape by suppressing CD70 and increasing metastatic ability by upregulating CD44 and VEGF (PMID:19638429)
• Data confirm previous observations of higher expression of CD70 in CD4+ T cells from patients with SLE, and suggest that increased Fyn protein content in CD4+ T cells can be associated with high SLE disease activity. (PMID:19955046)
• Epigenetic silencing of the TNFSF7 gene via hypermethylation of its proximal region may allow the benign and invasive MCF10 variants to escape immune surveillance. (PMID:20119871)
• CD70 is an important factor in the regulation of B-cell growth and differentiation by plasmacytoid dendritic cells. (PMID:20139096)
• the CD70-CD27 interaction may play an important role in inducing effective immune responses in dendritic cell-based immunotherapy. (PMID:20201989)
• In this review, CD27 and CD70 constitute a unique pair ligand and receptor pair which can activate innate and adaptive immunity as well as regulate immunity versus tolerance. (PMID:20699361)
• CD70 expression was significantly elevated and correlated with a decrease in CD70 promoter methylation in T4 lymphocytes from Sjogren’s syndrome patients as compared to levels in controls. (PMID:20724115)
• These data collectively establish a novel role for the CD70-CD27 axis in human gammadelta T-cell activation and hence open new perspectives for its modulation in clinical settings. (PMID:21182090)
• RFX1 recruits SUV39H1 to the promoter regions of the CD11a and CD70 genes in CD4(+) T cells, thereby regulating local H3K9 tri-methylation levels. (PMID:21192791)
• Stimulation of T cells expressing CD70-specific chimeric antigen receptors resulted in CD27 costimulation and recognition of CD70-positive tumor cell lines and primary tumor cells, as shown by IFN-gamma and IL-2 secretion and by tumor cell killing. (PMID:21304103)
• Th1 cell-specific CD70 expression may be involved in an amplification loop for polarized Th1-type immune responses through T cell-T cell interactions. (PMID:21490618)
• CD70 and CD11a facilitate the survival of T and B lymphocytes and indirectly enhance the destruction of platelets in immune thrombocytopenia. (PMID:21541792)
• concluded DNA methyltransferases(DNMTs) functioned as demethylases as MBD2, while increased DNMTs and MBD2 may cause demethylation and over expression of CD70 in CD4(+) T cells, potentially contributing to the pathogenesis of immune thrombocytopenia (PMID:21550117)
• These findings indicate that aberrant histone modifications within the TNFSF7 promoter may contribute to the development of lupus by increasing CD70 expression in CD4(+) T cells. (PMID:21865261)
• data indicate that the virus-induced selective upregulation of CD70 by Langerhans cells is the critical feature that enhances their capacity to induce effector CD8+ T cell responses compared with virus-primed dermal dendritic cells that lack CD70 (PMID:21880979)
• Findings suggest that demethylation of CD70 promoter region contributes to the overexpression of CD70 in CD4+ T cells and may contribute to autoimmune response in systemic sclerosis (SSc). (PMID:22306512)
• Regulation of Langerhans cell CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer. (PMID:22377764)
• These results indicate that CD27 and CD70 gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in a northern Chinese population. (PMID:22399187)
• The mean expression of CD70 was almost twice as high in renal cell carcinoma relative to normal kidney tissue (PMID:22401771)
• CD70 acts as a functional receptor binding to soluble CD27, resulting in lymphoma progression and that immunotherapy using anti-CD70 antibody may be a potential candidate for treatment for NNKTL. (PMID:23206232)
• These results highlight the importance of the CD27-CD70 costimulation pathway for the development of CMV-specific T cell immunity during acute and persistent infection. (PMID:23576505)
• CD70 is overexpressed in systemic lupus erythematosus CD4+ T cells, but expression is not linked to the typical clinical and serological parameters associated with the disease. (PMID:24238281)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd70	ENSMUSG00000019489
rattus_norvegicus	Cd70	ENSRNOG00000051015

Protein

Protein identifiers

CD70 antigen — P32970 (reviewed: P32970)

Alternative names: CD27 ligand, Tumor necrosis factor ligand superfamily member 7

All UniProt accessions (3): P32970, A0A0U5JA32, M0QZW2

UniProt curated annotations — full annotation on UniProt →

Function. 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. The CD70-CD27 signaling pathway mediates antigen-specific T cell activation and expansion which in turn provides immune surveillance of B cells.

Subunit / interactions. Homotrimer.

Subcellular location. Cell membrane.

Post-translational modifications. N-glycosylated.

Disease relevance. Lymphoproliferative syndrome 3 (LPFS3) [MIM:618261] An autosomal recessive, early-onset immunologic disorder characterized by increased susceptibility to Epstein-Barr virus infection in B cells, abnormal B-cell proliferation and increased susceptibility to B-cell malignancies, including Hodgkin lymphoma. Patients usually have lymphadenopathy and hypogammaglobulinemia, and may suffer from recurrent infections. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the tumor necrosis factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
P32970-1	1	yes
P32970-2	2

RefSeq proteins (2): NP_001243, NP_001317261 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006052	TNF_dom	Domain
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR021184	TNF_CS	Conserved_site
IPR042374	CD70	Family

Pfam: PF00229

UniProt features (48 total): mutagenesis site 20, strand 12, topological domain 2, sequence variant 2, turn 2, glycosylation site 2, disulfide bond 2, chain 1, transmembrane region 1, sequence conflict 1, domain 1, helix 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7KX0	X-RAY DIFFRACTION	2.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32970-F1	83.52	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 115–151, 133–168

Glycosylation sites (2): 63, 170

Mutagenesis-validated functional residues (20):

Position	Phenotype
61	decreased cd27 binding.
63	loss of protein expression.
65	loss of protein expression.
80	decreased cd27 binding.
83	loss of cd27 binding.
115	no effect on protein expression but loss of cd27 binding; when associated with a-151.
133	loss of protein expression; when associated with a-168.
135	decreased protein expression.
137	no effect on cd27 binding.
137	decreased cd27 binding.
144	decreased cd27 binding.
146	no effect on cd27 binding.
146	loss of cd27 binding.
148	decreased cd27 binding.
151	no effect on protein expression but loss of cd27 binding; when associated with a-115.
165	decreased protein expression.
168	loss of protein expression; when associated with a-133.
170	decreased expression and decreased binding to cd27.
178	decreased cd27 binding.
180	decreased cd27 binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5669034	TNFs bind their physiological receptors
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway

MSigDB gene sets: 237 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, BENPORATH_ES_WITH_H3K27ME3, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_B_CELL_PROLIFERATION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, NFKB_Q6, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (12): T cell mediated immunity (GO:0002456), B cell mediated immunity (GO:0019724), tumor necrosis factor-mediated signaling pathway (GO:0033209), T cell proliferation (GO:0042098), B cell proliferation (GO:0042100), positive regulation of T cell proliferation (GO:0042102), T cell activation (GO:0042110), adaptive immune memory response involving T cells and B cells (GO:0090717), extrinsic apoptotic signaling pathway (GO:0097191), CD27 signaling pathway (GO:0160162), immune response (GO:0006955), lymphocyte proliferation (GO:0046651)

GO Molecular Function (3): tumor necrosis factor receptor binding (GO:0005164), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
TNFR2 non-canonical NF-kB pathway	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	3
lymphocyte mediated immunity	2
lymphocyte proliferation	2
lymphocyte activation	2
cell surface receptor signaling pathway	2
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
T cell activation	1
B cell activation	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
adaptive immune memory response	1
apoptotic signaling pathway	1
immune system process	1
response to stimulus	1
mononuclear cell proliferation	1
tumor necrosis factor receptor superfamily binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD70	CD27	P26842	999
CD70	TNFRSF4	P43489	994
CD70	TNFRSF9	Q07011	985
CD70	CD28	P10747	979
CD70	CD40LG	P29965	964
CD70	ICOS	Q9Y6W8	903
CD70	TNFSF9	P41273	872
CD70	TNFRSF8	P28908	871
CD70	CD40	P25942	864
CD70	TNFSF4	P23510	836
CD70	CD80	P33681	805
CD70	TNFRSF18	Q9Y5U5	800
CD70	CD276	Q5ZPR3	784
CD70	TNFSF18	Q9UNG2	756
CD70	TNFRSF14	Q92956	745

IntAct

37 interactions, top by confidence:

A	B	Type	Score
CD70	CD27	psi-mi:“MI:0915”(physical association)	0.770
CD27	CD70	psi-mi:“MI:0407”(direct interaction)	0.770
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
CD70	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF17	TSPAN6	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
TNFRSF17	ZMPSTE24	psi-mi:“MI:0914”(association)	0.530
CD70	AKT1	psi-mi:“MI:2364”(proximity)	0.470
AKT1	CD70	psi-mi:“MI:0915”(physical association)	0.470
CD70	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KIR2DL4	GPR89A	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	SDCBP	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GLMN	CAND2	psi-mi:“MI:0914”(association)	0.350
GSDME	DDX39A	psi-mi:“MI:0914”(association)	0.350
HEATR3	PLD2	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
PPARA	SCD	psi-mi:“MI:0914”(association)	0.350
SPOP	CD70	psi-mi:“MI:2364”(proximity)	0.270
CD70	SPOP	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (249): CD70 (Affinity Capture-MS), KDM8 (Affinity Capture-MS), CD70 (Affinity Capture-MS), CD70 (Affinity Capture-MS), SEC14L1 (Affinity Capture-MS), CD70 (Affinity Capture-MS), TAMM41 (Affinity Capture-MS), FANCG (Affinity Capture-MS), NR2C2 (Affinity Capture-MS), PDXDC1 (Affinity Capture-MS), UTP20 (Affinity Capture-MS), XPO7 (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), TBC1D20 (Affinity Capture-MS), MAP2K3 (Affinity Capture-MS)

ESM2 similar proteins: A0EQL2, A2AJ76, A2AJA7, A6H8M9, A8T650, A8T682, A8T688, A8T6A6, D3ZLH5, F1QVU0, O08628, O75173, O88839, P04278, P08514, P08689, P0DV84, P15196, P20701, P29376, P32970, P38570, P60882, P80012, P97497, P97793, Q13444, Q15113, Q5RFQ8, Q5TM20, Q61398, Q63191, Q6UXC1, Q7Z304, Q7Z442, Q7Z7M0, Q8BNJ2, Q8CG85, Q8K1S7, Q8NBP7

Diamond homologs: O55237, P32970, Q3ZDR4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CD70	up-regulates	CD27	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cell surface receptor signaling pathway	5	9.7×	9e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

49 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	29
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
599337	NM_001252.5(CD70):c.535C>T (p.Arg179Ter)	Pathogenic
599338	NM_001252.5(CD70):c.250del (p.Ser84fs)	Pathogenic
599339	NM_001252.5(CD70):c.552CTT[1] (p.Phe186del)	Pathogenic

SpliceAI

280 predictions. Top by Δscore:

Variant	Effect	Δscore
19:6590836:CTCA:C	donor_loss	0.9900
19:6590837:TCA:T	donor_loss	0.9900
19:6590838:CA:C	donor_loss	0.9900
19:6590839:A:AC	donor_gain	0.9900
19:6590839:A:AT	donor_loss	0.9900
19:6590839:AC:A	donor_gain	0.9900
19:6590839:ACC:A	donor_gain	0.9900
19:6590840:C:CC	donor_gain	0.9900
19:6590840:CC:C	donor_gain	0.9900
19:6590840:CCC:C	donor_gain	0.9900
19:6590833:CAACT:C	donor_loss	0.9800
19:6590834:AACTC:A	donor_loss	0.9800
19:6590835:ACTCA:A	donor_loss	0.9800
19:6590839:ACCC:A	donor_gain	0.9700
19:6590840:CCCC:C	donor_gain	0.9700
19:6590840:CCCCA:C	donor_gain	0.9700
19:6586420:T:TC	acceptor_gain	0.9600
19:6590835:A:C	donor_gain	0.9600
19:6586405:CCTGG:C	acceptor_loss	0.9400
19:6586406:C:CG	acceptor_loss	0.9400
19:6586407:T:G	acceptor_loss	0.9400
19:6586413:C:CT	acceptor_gain	0.9300
19:6586415:C:CT	acceptor_gain	0.9300
19:6586406:C:CC	acceptor_gain	0.9100
19:6586403:GTC:G	acceptor_gain	0.8900
19:6586404:TC:T	acceptor_gain	0.8900
19:6586405:CC:C	acceptor_gain	0.8900
19:6586416:A:T	acceptor_gain	0.8900
19:6586420:T:C	acceptor_gain	0.8800
19:6586402:GGTC:G	acceptor_gain	0.8500

AlphaMissense

1218 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:6586377:C:A	W75C	0.999
19:6586377:C:G	W75C	0.999
19:6586047:G:C	F185L	0.998
19:6586047:G:T	F185L	0.998
19:6586049:A:G	F185L	0.998
19:6586161:G:C	F147L	0.997
19:6586161:G:T	F147L	0.997
19:6586162:A:C	F147C	0.997
19:6586163:A:G	F147L	0.997
19:6586347:G:C	F85L	0.997
19:6586347:G:T	F85L	0.997
19:6586348:A:C	F85C	0.997
19:6586349:A:G	F85L	0.997
19:6586102:A:T	L167H	0.996
19:6586379:A:G	W75R	0.996
19:6586379:A:T	W75R	0.996
19:6586108:T:A	D165V	0.995
19:6586292:A:C	Y104D	0.995
19:6586150:C:G	C151S	0.994
19:6586151:A:T	C151S	0.994
19:6586348:A:G	F85S	0.994
19:6586045:A:C	F186C	0.993
19:6586048:A:C	F185C	0.993
19:6586297:C:A	G102V	0.993
19:6586315:A:G	L96P	0.993
19:6586045:A:G	F186S	0.992
19:6586099:C:G	C168S	0.992
19:6586100:A:T	C168S	0.992
19:6586162:A:G	F147S	0.992
19:6586279:A:T	I108N	0.992

dbSNP variants (sampled 300 via entrez): RS1000117334 (19:6585301 T>A,C), RS1000189840 (19:6581438 C>T), RS1000340785 (19:6587814 A>G), RS1000350920 (19:6587561 T>C), RS1000446032 (19:6592423 G>C,T), RS1000777651 (19:6588051 G>A,T), RS1000811916 (19:6587333 A>G,T), RS1000872757 (19:6592365 C>T), RS1000925092 (19:6592123 A>C), RS1001875028 (19:6591085 C>A,T), RS1001897635 (19:6583763 T>C,G), RS1001927429 (19:6590853 G>C,T), RS1002046013 (19:6589090 C>G), RS1002266268 (19:6583397 G>A), RS1002811214 (19:6589410 G>A,T)

Disease associations

OMIM: gene MIM:602840 | disease phenotypes: MIM:618261

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
severe combined immunodeficiency due to CD70 deficiency	Definitive	AR

Mondo (1): severe combined immunodeficiency due to CD70 deficiency (MONDO:0034054)

Orphanet (1): EBV-induced lymphoproliferative disease due to CD70 deficiency (Orphanet:538958)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001433	Hepatosplenomegaly
HP:0001954	Recurrent fever
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0005523	Lymphoproliferative disorder
HP:0012189	Hodgkin lymphoma
HP:0032170	Severe varicella zoster infection
HP:0040218	Reduced total natural killer cell count
HP:0410297	Partial absence of specific antibody response to tetanus vaccine

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010042_37	Asthma	3.000000e-09
GCST010043_69	Asthma	2.000000e-08
GCST012489_143	Heel bone mineral density x serum urate levels interaction	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712913 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7259857	CD70		0.00	0

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	5
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Aflatoxin B1	increases methylation, affects expression, increases expression	3
Arsenic Trioxide	decreases expression, increases expression	2
Lipopolysaccharides	increases expression, affects cotreatment, decreases reaction	2
Valproic Acid	affects expression, decreases methylation	2
Sodium Selenite	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
lead acetate	decreases expression	1
VX-agent	increases expression	1
terbufos	increases methylation	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases expression, increases abundance	1
cupric chloride	decreases expression	1
triphenyltin	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
diallyl trisulfide	decreases expression	1
pentanal	increases expression	1
gardenoside	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
usnic acid	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1

Cellosaurus cell lines

6 cell lines: 2 cancer cell line, 2 spontaneously immortalized cell line, 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1MT	Abcam HeLa CD70 KO	Cancer cell line	Female
CVCL_E6PQ	Genomeditech CHO-K1 H_CD70	Spontaneously immortalized cell line	Female
CVCL_F1N4	HyCyte BT-549 KO-hCD70	Cancer cell line	Female
CVCL_XZ40	CHO-K1 human CD70	Spontaneously immortalized cell line	Female
CVCL_YM65	PHAi003-A	Induced pluripotent stem cell	Female
CVCL_YM66	PHAi003-B	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.