CD27

Summary

CD27 (CD27 molecule, HGNC:11922) is a protein-coding gene on chromosome 12p13.31, encoding CD27 antigen (P26842). Costimulatory immune-checkpoint receptor expressed at the surface of T-cells, NK-cells and B-cells which binds to and is activated by its ligand CD70/CD27L expressed by B-cells.

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.

Source: NCBI Gene 939 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lymphoproliferative syndrome 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 245 total — 9 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11922
Approved symbol	CD27
Name	CD27 molecule
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	S152, Tp55
Ensembl gene	ENSG00000139193
Ensembl biotype	protein_coding
OMIM	186711
Entrez	939

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000266557, ENST00000541233, ENST00000881846, ENST00000881847, ENST00000881848

RefSeq mRNA: 7 — MANE Select: NM_001242 NM_001242, NM_001413263, NM_001413264, NM_001413265, NM_001413266, NM_001413267, NM_001413268

CCDS: CCDS8545

Canonical transcript exons

ENST00000266557 — 6 exons

Exon	Start	End
ENSE00000936997	6444955	6445231
ENSE00000936998	6445424	6445555
ENSE00003464136	6451268	6451713
ENSE00003552867	6450541	6450630
ENSE00003579160	6450895	6451014
ENSE00003647122	6450173	6450352

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 98.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.3448 / max 502.6487, expressed in 168 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123665	4.2443	152
123667	2.2995	133
123666	0.4221	88
123664	0.2724	80
123668	0.1065	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	98.12	gold quality
spleen	UBERON:0002106	95.94	gold quality
vermiform appendix	UBERON:0001154	94.69	gold quality
bone marrow cell	CL:0002092	92.59	gold quality
granulocyte	CL:0000094	90.93	gold quality
blood	UBERON:0000178	90.66	gold quality
duodenum	UBERON:0002114	88.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.37	silver quality
mucosa of transverse colon	UBERON:0004991	85.85	gold quality
bone marrow	UBERON:0002371	85.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.06	gold quality
small intestine	UBERON:0002108	83.96	gold quality
tonsil	UBERON:0002372	82.43	gold quality
rectum	UBERON:0001052	81.57	gold quality
colonic epithelium	UBERON:0000397	79.21	gold quality
gall bladder	UBERON:0002110	78.94	gold quality
saliva-secreting gland	UBERON:0001044	78.36	gold quality
transverse colon	UBERON:0001157	78.12	gold quality
minor salivary gland	UBERON:0001830	78.09	gold quality
intestine	UBERON:0000160	75.44	gold quality
fundus of stomach	UBERON:0001160	73.24	gold quality
colon	UBERON:0001155	73.22	gold quality
urinary bladder	UBERON:0001255	72.29	gold quality
right lobe of thyroid gland	UBERON:0001119	72.07	gold quality
body of stomach	UBERON:0001161	72.06	gold quality
left lobe of thyroid gland	UBERON:0001120	71.85	gold quality
thyroid gland	UBERON:0002046	71.33	gold quality
right coronary artery	UBERON:0001625	70.58	gold quality
stromal cell of endometrium	CL:0002255	70.43	gold quality
stomach	UBERON:0000945	69.60	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	1063.99
E-GEOD-106540	yes	1014.09
E-GEOD-139324	yes	1011.82
E-CURD-79	yes	964.95
E-CURD-88	yes	427.88
E-MTAB-8911	yes	317.63
E-HCAD-4	yes	105.85
E-MTAB-6701	yes	76.56
E-MTAB-9467	yes	70.45
E-HCAD-1	yes	58.46
E-CURD-122	yes	50.11
E-HCAD-8	yes	48.33
E-CURD-120	yes	46.48
E-MTAB-8410	yes	45.61
E-MTAB-8142	yes	39.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BCL2	Activation
BCL2L1	Activation
BIK	Repression

Upstream regulators (CollecTRI, top): PRDM1

miRNA regulators (miRDB)

19 targeting CD27, 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-6768-5P	99.92	67.36	1942
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-1288-3P	96.86	66.95	536
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-193A-5P	95.70	65.33	613

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Functionally differentiated Vgamma9delta2+ T cells lack CD27 expression and are found in reduced numbers in immunocompromised hosts (such as healthy newborns and HIV-infected adults) and during active pulmonary tuberculosis. (PMID:11801693)
• Increased levels of soluble CD27 in the cerebrospinal fluid are not diagnostic for leptomeningeal involvement by lymphoid malignancies.The positive predictive value of sCD27 determination for LI was only 54%, but the negative predictive value was 92%. (PMID:11976819)
• intragraft gene expression is a risk factor for acute cardiac allograft rejection (PMID:12009595)
• IL-10 enhances B-cell IgE synthesis by promoting differentiation into plasma cells, a process that is inhibited by CD27/CD70 interaction (PMID:12197885)
• CD27 and CD40 co-stimulatory signals regulated the p53-amplified apoptotic pathway in B cells through the inhibition of p53-independent apoptotic pathway primarily induced by BCR ligation (PMID:12324477)
• CD27(-) effector CD8(+) T cells might be required for adequate control of chronic viral infection and prevention of disease development. (PMID:12464570)
• CD148 and CD27 are expressed in a wide range of B cell non-Hodgkin’s lymphomas and do not serve to distinguish between neoplastic cells of naive and memory B cell derivation (PMID:12685844)
• In indolent lymphomas, sCD27 proved to be a powerful marker to predict progression-free survival (p = 0.008). (PMID:12743427)
• Systemic lupus erythematosus flares may relate to the retention of CD27+ memory B cells. (review) (PMID:15230280)
• Signals through CD70 in B lymphocytes of CD70 transgenic mice result in enhanced cell cycle entry while preventing differentiation into IgG-secreting plasma cells. (PMID:15356138)
• In primary biliary cirrhosis CpG led to a markedly high frequency of intracellular IgM-positive B cells, associated with high levels of synthesized IgM and identified to be a function of CD27(+) memory B cells. (PMID:15685542)
• functional and lineage relationships of three distinct memory CD4 subpopulations distinguished by their expression of the cysteine chemokine receptor CCR7 and the TNFR family member CD27 (PMID:16272303)
• Interaction of CD70 with CD27 plays a direct role in T cell activation mediated by IL-2. (PMID:16751420)
• In systemic lupus erythematosus (SLE) patients, significant increases of CCR7-, CD27- and CCR7-, CD27+ and a reduction of CCR7+, CD27+ CD4 memory T cells were found. (PMID:16802356)
• The memory B cell reservoir extends beyond the CD27+ compartment because B cells expressing surface IgG, but not CD27, have been found in human blood and provide further insights into B cell disorders of unknown etiology. (PMID:16951333)
• In systemic lupus erythematosus, an increased frequency of CD27-negative memory cells is significantly associated with higher disease activity index and disease-specific autoantibodies. (PMID:17475894)
• 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)
• Failure to increase surface expression of costimulatory molecules CD27 and CD28 following stimulation may contribute to naive T cell impairment in HIV infection. (PMID:17785788)
• marginal zone-like IgM(+)CD27(+) B cells are clonally expanded in certain subjects with mixed cryoglobulinemia (MC) offers insight into mechanisms of HCV-associated MC and B-cell malignancy (PMID:17942751)
• Expression defines phenotypic stages in B cell precursor development. (PMID:18005092)
• A functional role for sCD27 in WM(Waldenstrom macroglobulinemia) pathogenesis, along with its utility as a surrogate marker of disease and a target in the treatment of WM. (PMID:18216294)
• Lack of CD27 expression on natural killer (NK) cells is associated with high cytolytic function and, in combination with CD56, allows a better definition of cytotoxic effector cells. (PMID:18322179)
• a homogeneous subset of CD27-,IgD-,CD95+ memory B cells with an activated phenotype was identified in lupus patients (PMID:18512812)
• CD70/CD27 interaction provides a critical stimulus for expanding effector T cells, enhancing their cytotoxic activity and improving the antileukemic effector response. (PMID:19109206)
• The absolute number of B lymphocytes and the percentage of naive cells (CD23-/CD27-) decreased with age whereas there was an increase in memory cells (CD27+). (PMID:19290077)
• 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)
• A double-negative (IgD-CD27-) B cell population is increased in the peripheral blood of elderly people. (PMID:19698733)
• CD19(+)IgM(+)D(+)CD27(-ve) memory B cells may have a distinct lineage and function, and seem relevant to understanding origins of malignant B cells, in particular those of hairy cell leukemia cells, which display mutated V genes yet lack CD27 expression (PMID:19776762)
• higher proportion of protein-expressing B-cells in the blood of patients with systemic lupus erythematosus (PMID:19866343)
• the CD70-CD27 interaction may play an important role in inducing effective immune responses in dendritic cell-based (PMID:20201989)
• The CD27(+) B-cell population was found to highly express CXCR3 in chronic hepatitis C (CHC), thus suggesting that the CD27(+) B-cell population was recruited from peripheral blood to the inflammatory site of the liver of CHC. (PMID:20377416)
• Compared with tuberculin-positive controls, patients with bacterial culture-positive pulmonary TB had significantly reduced CD27 expression on antigen-specific CD4 T cells (PMID:20393787)
• In this review, CD27 and CD70 constitute a unique ligand and receptor pair which can activate innate and adaptive immunity as well as regulate immunity versus tolerance. (PMID:20699361)
• no correlation between expression on T-lymphocytes and sera levels in children with asthma (PMID:20800938)
• CD27 may have a role in infection in systemic lupus erythematosus (PMID:20879061)
• 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)
• CD27(+) lymphocytes represent abnormal mononuclear cell populations in atrophic oral lichen planus (OLP) lesions indicating forms of OLP might exist with different pathogenesis, despite similar histology and clinical behavior. (PMID:21237436)
• CD27 signalling does influence T(H) cell differentiation. (PMID:21277898)
• Data show that CD27(+)/IgD(-)/ZAP70(+) memory B cells accumulate preferentially in the joints of RA, suggesting a dynamic maturation of the B cells in this compartment. (PMID:21607290)
• down-regulation of CD27 on MTB-specific CD4 T cell could be used as a biomarker of active TB, potentially preceding clinical TB disease (PMID:22087280)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdr	ENSDARG00000004392
danio_rerio	tnfrsfa	ENSDARG00000004451
danio_rerio	cd40	ENSDARG00000054968
danio_rerio	nradd	ENSDARG00000057143
danio_rerio	tnfrsf1b	ENSDARG00000070165
danio_rerio	tnfrsf11a	ENSDARG00000087804
mus_musculus	Cd27	ENSMUSG00000030336
rattus_norvegicus	Cd27	ENSRNOG00000027466

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), TNFRSF1A (ENSG00000067182), CD40 (ENSG00000101017), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF10B (ENSG00000120889), TNFRSF8 (ENSG00000120949), TNFRSF11A (ENSG00000141655), TNFRSF21 (ENSG00000146072), TNFRSF14 (ENSG00000157873), TNFRSF11B (ENSG00000164761), TNFRSF10D (ENSG00000173530), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

CD27 antigen — P26842 (reviewed: P26842)

Alternative names: CD27L receptor, T-cell activation antigen CD27, T14, Tumor necrosis factor receptor superfamily member 7

All UniProt accessions (1): P26842

UniProt curated annotations — full annotation on UniProt →

Function. Costimulatory immune-checkpoint receptor expressed at the surface of T-cells, NK-cells and B-cells which binds to and is activated by its ligand CD70/CD27L expressed by B-cells. The CD70-CD27 signaling pathway mediates antigen-specific T-cell activation and expansion which in turn provides immune surveillance of B-cells. Mechanistically, CD70 ligation activates the TRAF2-PTPN6 axis that subsequently inhibits LCK phosphorylation to promote phenotypic and transcriptional adaptations of T-cell memory. In addition, activation by CD70 on early progenitor cells provides a negative feedback signal to leukocyte differentiation during immune activation and thus modulates hematopoiesis. Negatively regulates the function of Th2 lymphocytes in the adipose tissue.

Subunit / interactions. Homodimer. Interacts with SIVA1; may play a role in apoptosis through association with SIVA1. Interacts with TRAF2. Interacts ith PTPN6.

Subcellular location. Cell membrane.

Tissue specificity. Found in most T-lymphocytes.

Post-translational modifications. Phosphorylated. N-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (7): NP_001233, NP_001400192, NP_001400193, NP_001400194, NP_001400195, NP_001400196, NP_001400197 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR022328	TNFR_7	Family
IPR034000	TNFRSF7_N	Domain
IPR053126	CD27_receptor	Family

Pfam: PF00020

UniProt features (46 total): mutagenesis site 10, strand 10, disulfide bond 8, sequence variant 3, repeat 3, glycosylation site 2, topological domain 2, turn 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5TL5	X-RAY DIFFRACTION	1.8
8DS5	X-RAY DIFFRACTION	1.93
7KX0	X-RAY DIFFRACTION	2.69
5TLK	X-RAY DIFFRACTION	2.7
5TLJ	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26842-F1	71.79	0.42

Antibody-complex structures (SAbDab): 4 — 5TL5, 5TLJ, 5TLK, 8DS5

Functional residue map

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

Post-translational modifications (1): 219

Disulfide bonds (8): 27–39, 40–53, 43–62, 65–81, 84–96, 87–104, 106–120, 112–117

Glycosylation sites (2): 95, 127

Mutagenesis-validated functional residues (10):

Position	Phenotype
30	decreased cd70 binding.
74	decreased cd70 binding.
82	loss of cd70 binding.
83	decreased cd70 binding.
88	decreased cd70 binding.
95	no effect on cd70 binding.
113	decreased cd70 binding.
114	decreased cd70 binding.
118	decreased cd70 binding.
121	decreased cd70 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: 392 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, WALLACE_PROSTATE_CANCER_RACE_UP, MCLACHLAN_DENTAL_CARIES_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_B_CELL_ACTIVATION, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GGGTGGRR_PAX4_03

GO Biological Process (14): cell surface receptor signaling pathway (GO:0007166), immunoglobulin mediated immune response (GO:0016064), T cell activation (GO:0042110), negative regulation of apoptotic process (GO:0043066), response to ethanol (GO:0045471), positive regulation of B cell differentiation (GO:0045579), positive regulation of T cell differentiation (GO:0045582), positive regulation of JNK cascade (GO:0046330), negative regulation of T cell apoptotic process (GO:0070233), adaptive immune memory response involving T cells and B cells (GO:0090717), extrinsic apoptotic signaling pathway (GO:0097191), CD27 signaling pathway (GO:0160162), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), apoptotic process (GO:0006915)

GO Molecular Function (3): transmembrane signaling receptor activity (GO:0004888), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), 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
cellular anatomical structure	3
positive regulation of lymphocyte differentiation	2
cell surface receptor signaling pathway	2
apoptotic signaling pathway	2
signal transduction	1
B cell mediated immunity	1
lymphocyte activation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to alcohol	1
B cell differentiation	1
regulation of B cell differentiation	1
positive regulation of B cell activation	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of T cell activation	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
negative regulation of lymphocyte apoptotic process	1
T cell apoptotic process	1
regulation of T cell apoptotic process	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
adaptive immune memory response	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
programmed cell death	1
execution phase of apoptosis	1
signaling receptor activity	1
cysteine-type endopeptidase regulator activity involved in apoptotic process	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

2304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD27	CD70	P32970	999
CD27	CD86	P42081	992
CD27	CD80	P33681	989
CD27	TNFSF4	P23510	986
CD27	TNFSF9	P41273	982
CD27	A0A087X1L8	A0A087X1L8	964
CD27	ICOSLG	O75144	964
CD27	SIVA1	O15304	950
CD27	TNFRSF8	P28908	934
CD27	CD19	P15391	932
CD27	TNFRSF4	P43489	929
CD27	CD4	P01730	927
CD27	TNFSF8	P32971	920
CD27	CD40LG	P29965	920
CD27	CD40	P25942	919

IntAct

29 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
CD27	SIVA1	psi-mi:“MI:0915”(physical association)	0.630
SIVA1	CD27	psi-mi:“MI:0915”(physical association)	0.630
ACTN2	CD27	psi-mi:“MI:0915”(physical association)	0.560
CD27	CIB1	psi-mi:“MI:0915”(physical association)	0.560
CD27	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
rep	CD27	psi-mi:“MI:0915”(physical association)	0.560
CD27	TRAF2	psi-mi:“MI:0915”(physical association)	0.550
CD27	UHRF2	psi-mi:“MI:0915”(physical association)	0.400
CD27	CIB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (119): C1GALT1 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), ADCK4 (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CTNNA2 (Affinity Capture-MS), FAM115C (Affinity Capture-MS), TTYH3 (Affinity Capture-MS), ADCY9 (Affinity Capture-MS), SCAMP1 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), TRAF2 (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), C4orf32 (Affinity Capture-MS)

ESM2 similar proteins: A4D2P6, A5PJC7, O14836, O19131, P07174, P08138, P15725, P18519, P19438, P20333, P22273, P22934, P25118, P26842, P32927, P41272, P42701, P43489, P47741, P49796, P50555, P52734, P98174, Q01114, Q07303, Q08351, Q13477, Q14162, Q3U4N7, Q3UV31, Q60943, Q60953, Q6AZ51, Q6UWJ8, Q6WN34, Q8BH06, Q8BUM9, Q8BX43, Q8K5A9, Q8NAC3

Diamond homologs: O35305, P20334, P26842, Q07011, Q3ZTK5, Q9Y6Q6, P41272, Q63199, Q7YRL5, Q92956, A5D7R1, O77736, P25445, P25446, P25942, P43489, P47741, P51867, Q3LRP1, Q80WM9, Q9BDN0, Q9BDN4, Q9BDP2, Q9TSN4, O00300, O08712, O08727, O75509, P20333, P27512, Q28203, Q8SQ34, O19131, O95407, P0DSV7, P0DSV8, P0DTN0, P15725, P22934, P25119

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CD70	up-regulates	CD27	binding
CD27	“up-regulates quantity by expression”	BCL2	“transcriptional regulation”
CD27	“up-regulates quantity by expression”	BCL2L1	“transcriptional regulation”
CD27	“down-regulates quantity by repression”	BIK	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	6
Uncertain significance	113
Likely benign	81
Benign	15

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1701181	NM_001242.5(CD27):c.266_267del (p.Ser89fs)	Pathogenic
1961237	NM_001242.5(CD27):c.441T>A (p.Tyr147Ter)	Pathogenic
2126450	NM_001242.5(CD27):c.256del (p.His86fs)	Pathogenic
3244333	NC_000012.11:g.(?6554691)(6560069_?)dup	Pathogenic
3657123	NM_001242.5(CD27):c.399del (p.Gln134fs)	Pathogenic
3690987	NM_001242.5(CD27):c.410del (p.Ser137fs)	Pathogenic
3696331	NM_001242.5(CD27):c.421C>T (p.Gln141Ter)	Pathogenic
578414	NM_001242.5(CD27):c.239dup (p.His80fs)	Pathogenic
827694	NM_001242.5(CD27):c.250dup (p.Cys84fs)	Pathogenic
1339535	NM_001242.5(CD27):c.98G>A (p.Trp33Ter)	Likely pathogenic
3244332	NC_000012.11:g.(?6559440)(6560401_?)del	Likely pathogenic
4682803	GRCh37/hg19 12p13.31(chr12:6071100-6619414)x1	Likely pathogenic
4701655	NM_001242.5(CD27):c.538+1G>C	Likely pathogenic
4770039	NM_001242.5(CD27):c.538+1G>A	Likely pathogenic
636587	NM_001242.5(CD27):c.780_781del (p.Ter261SerextTer?)	Likely pathogenic

SpliceAI

799 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6450307:GCCC:G	donor_gain	1.0000
12:6450539:A:AG	acceptor_gain	1.0000
12:6450540:G:GG	acceptor_gain	1.0000
12:6450540:GA:G	acceptor_gain	1.0000
12:6450540:GAGAT:G	acceptor_gain	1.0000
12:6450626:GCCAC:G	donor_gain	1.0000
12:6450627:CCAC:C	donor_gain	1.0000
12:6450627:CCACG:C	donor_loss	1.0000
12:6450628:CACG:C	donor_loss	1.0000
12:6450629:AC:A	donor_gain	1.0000
12:6450629:ACGTG:A	donor_loss	1.0000
12:6450630:CGTG:C	donor_loss	1.0000
12:6450631:G:GG	donor_gain	1.0000
12:6450632:TGA:T	donor_loss	1.0000
12:6450633:GAG:G	donor_loss	1.0000
12:6450888:A:AG	acceptor_gain	1.0000
12:6450889:T:G	acceptor_gain	1.0000
12:6450892:CA:C	acceptor_loss	1.0000
12:6450893:A:AG	acceptor_gain	1.0000
12:6450894:G:GT	acceptor_gain	1.0000
12:6450894:GC:G	acceptor_gain	1.0000
12:6450894:GCC:G	acceptor_gain	1.0000
12:6450894:GCCC:G	acceptor_gain	1.0000
12:6450894:GCCCA:G	acceptor_gain	1.0000
12:6451015:G:GG	donor_gain	1.0000
12:6448161:GCA:G	donor_gain	0.9900
12:6450169:CCAGG:C	acceptor_loss	0.9900
12:6450170:CAGGT:C	acceptor_loss	0.9900
12:6450171:A:AG	acceptor_gain	0.9900
12:6450171:A:G	acceptor_loss	0.9900

AlphaMissense

1697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6445498:T:C	F71L	0.994
12:6445500:C:A	F71L	0.994
12:6445500:C:G	F71L	0.994
12:6445528:T:A	C81S	0.984
12:6445529:G:C	C81S	0.984
12:6445429:T:C	F48L	0.983
12:6445431:C:A	F48L	0.983
12:6445431:C:G	F48L	0.983
12:6445480:T:A	C65S	0.983
12:6445481:G:C	C65S	0.983
12:6445482:C:G	C65W	0.981
12:6445529:G:A	C81Y	0.981
12:6445481:G:A	C65Y	0.979
12:6450214:T:A	C104S	0.977
12:6450215:G:C	C104S	0.977
12:6450190:T:A	C96S	0.976
12:6450191:G:C	C96S	0.976
12:6445480:T:C	C65R	0.975
12:6445546:T:A	C87S	0.975
12:6445547:G:C	C87S	0.975
12:6450192:C:G	C96W	0.975
12:6445499:T:G	F71C	0.974
12:6445530:T:G	C81W	0.973
12:6445537:T:A	C84S	0.973
12:6445538:G:C	C84S	0.973
12:6450238:T:A	C112S	0.973
12:6450239:G:C	C112S	0.973
12:6445222:T:A	C43S	0.972
12:6445223:G:C	C43S	0.972
12:6445547:G:A	C87Y	0.972

dbSNP variants (sampled 300 via entrez): RS1001010800 (12:6449204 C>A,T), RS1001127637 (12:6444794 G>A), RS1001185463 (12:6449537 T>A), RS1001471174 (12:6444419 C>T), RS1001546591 (12:6449501 C>T), RS1001721549 (12:6449811 T>C), RS1002424631 (12:6444692 G>A), RS1003016298 (12:6447581 C>G), RS1003103813 (12:6447735 T>TA), RS1003429706 (12:6446061 GT>G,GTT), RS1003565744 (12:6445858 G>A,C), RS1003658742 (12:6451927 G>T), RS1003660100 (12:6451332 G>A,T), RS1003722454 (12:6451291 C>A,G), RS1003929588 (12:6451019 G>C)

Disease associations

OMIM: gene MIM:186711 | disease phenotypes: MIM:615122, MIM:300755

GenCC curated gene-disease

Disease	Classification	Inheritance
lymphoproliferative syndrome 2	Strong	Autosomal recessive
autosomal recessive lymphoproliferative disease	Supportive	Autosomal recessive

Mondo (5): lymphoproliferative syndrome 2 (MONDO:0014054), autoinflammatory syndrome (MONDO:0019751), combined immunodeficiency (MONDO:0015131), immunodeficiency disease (MONDO:0021094), (MONDO:0016536)

Orphanet (3): Combined immunodeficiency due to CD27 deficiency (Orphanet:238505), Autoinflammatory syndrome (Orphanet:93665), Combined T and B cell immunodeficiency (Orphanet:101972)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000155	Oral ulcer
HP:0000554	Uveitis
HP:0001433	Hepatosplenomegaly
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0001876	Pancytopenia
HP:0001915	Aplastic anemia
HP:0001945	Fever
HP:0002240	Hepatomegaly
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0005523	Lymphoproliferative disorder
HP:0006532	Recurrent pneumonia
HP:0012156	Hemophagocytosis
HP:0012189	Hodgkin lymphoma
HP:0020072	Persistent EBV viremia
HP:0031381	Decreased mitogen-induced T-cell proliferation
HP:0032170	Severe varicella zoster infection
HP:0033508	EBV meningitis
HP:0033509	EBV encephalitis
HP:0100806	Sepsis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003044_41	Crohn’s disease	1.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713333 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Tumour necrosis factor (TNF) receptor family

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression, decreases methylation	2
Nickel	increases expression	2
bisphenol A	increases expression	1
VX-agent	increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
poly(propyleneimine)	decreases expression	1
licochalcone B	increases expression	1
bisphenol S	affects expression, increases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	increases expression	1
Zoledronic Acid	affects expression	1
Arsenic Trioxide	increases expression	1
alpha-Chlorohydrin	increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydroxychloroquine	affects cotreatment, decreases expression	1
Menthol	increases expression	1
Methotrexate	affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Paraquat	decreases expression	1
Pyrethrins	decreases expression	1
Sulfasalazine	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Trichloroethylene	decreases expression	1
Valproic Acid	increases methylation	1
Simvastatin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4677431	Binding	Binding affinity to human Fc-tagged CD27 at 500 nM measured after 600 sec by biolayer interferometry	Design, Synthesis, and Biological Evaluation of Linear Aliphatic Amine-Linked Triaryl Derivatives as Potent Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction with Promising Antitumor Effects In Vivo. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1BK	Abcam Raji CD27 KO	Cancer cell line	Male
CVCL_E8F1	Jurkat-Lucia hCD27	Cancer cell line	Male
CVCL_KA26	CHO-K1/CD27	Spontaneously immortalized cell line	Female
CVCL_XZ55	HT1080 human CD27	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001542	PHASE4	COMPLETED	Fluconazole Prophylaxis of Thrush in AIDS
NCT00144157	PHASE4	COMPLETED	Open Label Study of NVP+CBV Treatment in Women Who Have Received sdNVP for the pMTCT of HIV
NCT00162643	PHASE4	UNKNOWN	PI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00273988	PHASE4	COMPLETED	Pharmacokinetic Study of Interaction Between Nevirapine and Methadone in HIV-1 Infected, Opioid-dependent Adults
NCT00981318	PHASE4	TERMINATED	Pilot Assessment of Lopinavir/Ritonavir and Maraviroc
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01090102	PHASE4	COMPLETED	Mesalamine to Reduce T Cell Activation in HIV Infection
NCT01147042	PHASE4	TERMINATED	Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease
NCT01230580	PHASE4	UNKNOWN	Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
NCT01465958	PHASE4	COMPLETED	Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
NCT02274662	PHASE4	COMPLETED	Expanded Access Protocol Thymus Transplantation
NCT02348177	PHASE4	COMPLETED	Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
NCT02396979	PHASE4	COMPLETED	Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02490956	PHASE4	UNKNOWN	Diagnostic Immunization With Rabies Vaccine in Patients With PID
NCT02503293	PHASE4	COMPLETED	A Study to Compare Quality of Life and Satisfaction in Primary Immunodeficient Patients Treated With Subcutaneous Injections of Gammanorm® 165 mg/mL Administered With Two Different Delivery Devices: Injections Using Pump or Rapid Push
NCT02881437	PHASE4	COMPLETED	IgG Level in Primary Immunodeficiency Switching From Standard SCIG to Every Other Week HyQvia
NCT03033745	PHASE4	COMPLETED	Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT04192487	PHASE4	COMPLETED	Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04566692	PHASE4	COMPLETED	A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
NCT05493969	PHASE4	NOT_YET_RECRUITING	Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
NCT06576024	PHASE4	COMPLETED	Immunogenicity and Safety of Inactivated Hepatitis A Vaccine in HIV-infected People
NCT06634641	PHASE4	RECRUITING	Clozapine-related Immunodeficiency in Parkinsons Disease
NCT07076446	PHASE4	ACTIVE_NOT_RECRUITING	An Open-label, Multicenter Study to Assess the Pharmacokinetics (PK), Safety, and Tolerability of Subcutaneous IgPro20 in Immunoglobulin (IG) Treatment-naïve Participants With Primary Immunodeficiency (PID)
NCT00000118	PHASE3	COMPLETED	Ganciclovir Implant Study for Cytomegalovirus Retinitis
NCT00000134	PHASE3	COMPLETED	Studies of the Ocular Complications of AIDS (SOCA)–Cytomegalovirus Retinitis Retreatment Trial (CRRT)
NCT00000590	PHASE3	COMPLETED	Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
NCT00001267	PHASE3	COMPLETED	A Randomized Pilot Study for the Treatment of AIDS or AIDS Related Complex With an Alternating or Simultaneous Combination Regimen of AZT and 2’,3’-Dideoxyinosine
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00144183	PHASE3	COMPLETED	A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)
NCT00243568	PHASE3	WITHDRAWN	Vicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT00474370	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04889AM8)(COMPLETED)
NCT00478231	PHASE3	COMPLETED	Multicenter, Safety Study Of Maraviroc
NCT00523211	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04405AM5)
NCT00698334	PHASE3	COMPLETED	Efficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis
NCT00966160	PHASE3	COMPLETED	CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
NCT01363011	PHASE3	COMPLETED	Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
NCT01440569	PHASE3	COMPLETED	Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
NCT01475838	PHASE3	COMPLETED	Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients