CD27

CD27 molecule, the group of CD molecules|Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 12:6444955-6451718

Previous symbols: [ "TNFRSF7" ]

Links

ENSG00000139193 ∙ NCBI:939 ∙ OMIM:186711 ∙ HGNC:11922 ∙ Uniprot:P26842 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lymphoproliferative syndrome 2 (Moderate), mode of inheritance: AR
• autosomal recessive lymphoproliferative disease (Supportive), mode of inheritance: AR
• lymphoproliferative syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lymphoproliferative syndrome 2	AR	Allergy/Immunology/Infectious; Hematologic; Oncologic	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	Allergy/Immunology/Infectious; Hematologic; Oncologic	22197273; 22365582; 22801960

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD27 gene.

• Lymphoproliferative syndrome 2 (6 variants)
• not provided (2 variants)
• Combined immunodeficiency (1 variants)
• Immunodeficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD27 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				49		49
missense	1		90		2	93
nonsense	2	1				3
start loss						0
frameshift	5	2	1			8
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	8		11
non coding			1	19	6	26
Total	8	3	92	68	8

Highest pathogenic variant AF is 0.0000131

Variants in CD27

This is a list of pathogenic ClinVar variants found in the CD27 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-6445096-A-G		not specified	Uncertain significance (Nov 03, 2022)
12-6445102-C-T		Lymphoproliferative syndrome 2	Uncertain significance (Dec 04, 2023)
12-6445103-G-A		Lymphoproliferative syndrome 2	Uncertain significance (Jul 20, 2022)
12-6445110-T-A		Lymphoproliferative syndrome 2	Uncertain significance (Mar 04, 2020)
12-6445110-T-G		Lymphoproliferative syndrome 2	Uncertain significance (Jan 20, 2022)
12-6445117-T-C		Lymphoproliferative syndrome 2	Uncertain significance (Sep 29, 2019)
12-6445117-T-G		Lymphoproliferative syndrome 2	Uncertain significance (Dec 29, 2021)
12-6445119-G-A		Lymphoproliferative syndrome 2	Pathogenic (Mar 01, 2012)
12-6445120-C-T		Lymphoproliferative syndrome 2	Likely benign (Jun 04, 2023)
12-6445125-C-T		Lymphoproliferative syndrome 2 • Autoinflammatory syndrome • CD27-related disorder	Benign/Likely benign (Jan 29, 2024)
12-6445126-G-A		Lymphoproliferative syndrome 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 06, 2023)
12-6445132-G-A		Lymphoproliferative syndrome 2 • Autoinflammatory syndrome • not specified	Uncertain significance (Aug 23, 2022)
12-6445132-G-T		Lymphoproliferative syndrome 2 • Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
12-6445133-G-T		Lymphoproliferative syndrome 2	Uncertain significance (Aug 23, 2022)
12-6445137-C-A		Lymphoproliferative syndrome 2	Likely benign (Jul 11, 2019)
12-6445146-G-C		CD27-related disorder	Likely benign (Oct 30, 2020)
12-6445158-T-A		Lymphoproliferative syndrome 2	Likely benign (Aug 10, 2023)
12-6445162-G-A		Lymphoproliferative syndrome 2	Uncertain significance (Dec 14, 2022)
12-6445167-C-G		Lymphoproliferative syndrome 2	Likely benign (Jun 21, 2023)
12-6445168-A-G		Lymphoproliferative syndrome 2	Uncertain significance (Mar 02, 2022)
12-6445172-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)
12-6445183-A-G		Lymphoproliferative syndrome 2	Uncertain significance (Sep 17, 2021)
12-6445193-G-A		Lymphoproliferative syndrome 2	Likely pathogenic (Dec 28, 2021)
12-6445196-C-T		Lymphoproliferative syndrome 2	Uncertain significance (Sep 02, 2021)
12-6445201-G-A		Lymphoproliferative syndrome 2	Uncertain significance (Oct 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD27	protein_coding	protein_coding	ENST00000266557	6	6852

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0100	0.948	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.132	148	153	0.970	0.00000841	1679
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000970	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.432

Intolerance Scores

• loftool: 0.361
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.66

Haploinsufficiency Scores

• pHI: 0.152
• hipred: Y
• hipred_score: 0.594
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.743

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cd27
• Phenotype: immune system phenotype; hematopoietic system phenotype; cellular phenotype

Gene ontology

• 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;response to ethanol;positive regulation of B cell differentiation;positive regulation of T cell differentiation;positive regulation of JNK cascade;negative regulation of T cell apoptotic process;extrinsic apoptotic signaling pathway;positive regulation of NIK/NF-kappaB signaling
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;external side of plasma membrane
• Molecular function: transmembrane signaling receptor activity;protein binding;cysteine-type endopeptidase inhibitor activity involved in apoptotic process