TNFSF12

TNF superfamily member 12, the group of Tumor necrosis factor superfamily

Basic information

Region (hg38): 17:7548507-7557890

Links

ENSG00000239697 ∙ NCBI:8742 ∙ OMIM:602695 ∙ HGNC:11927 ∙ Uniprot:O43508 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• common variable immunodeficiency (Supportive), mode of inheritance: AD
• common variable immunodeficiency (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNFSF12 gene.

• Common variable immunodeficiency (172 variants)
• not provided (10 variants)
• not specified (4 variants)
• TNFSF12-related condition (4 variants)
• Inborn genetic diseases (3 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNFSF12 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				45	7	52
missense			83			83
nonsense			4			4
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			5	6	1	12
non coding				18	4	22
Total	0	0	90	63	11

Variants in TNFSF12

This is a list of pathogenic ClinVar variants found in the TNFSF12 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-7549159-C-G			Likely benign (Jun 01, 2018)
17-7549164-G-C		Common variable immunodeficiency	Uncertain significance (Oct 14, 2022)
17-7549176-G-A		Common variable immunodeficiency	Uncertain significance (Aug 28, 2021)
17-7549179-G-A		Common variable immunodeficiency	Uncertain significance (Jul 22, 2021)
17-7549182-G-C		Common variable immunodeficiency	Uncertain significance (Jun 14, 2023)
17-7549188-G-C		Common variable immunodeficiency	Uncertain significance (Nov 28, 2023)
17-7549191-G-A		Common variable immunodeficiency	Uncertain significance (Aug 24, 2021)
17-7549195-G-A		Common variable immunodeficiency	Likely benign (Aug 30, 2023)
17-7549196-G-A		Common variable immunodeficiency • See cases	Uncertain significance (Jan 29, 2024)
17-7549199-C-A		Common variable immunodeficiency	Uncertain significance (Nov 27, 2023)
17-7549204-C-A		Common variable immunodeficiency	Likely benign (Nov 15, 2022)
17-7549207-C-T		Common variable immunodeficiency	Likely benign (Nov 06, 2023)
17-7549208-G-A		Common variable immunodeficiency	Uncertain significance (Jan 06, 2024)
17-7549212-T-C		Common variable immunodeficiency	Uncertain significance (Sep 15, 2022)
17-7549213-G-C		Common variable immunodeficiency	Likely benign (Feb 20, 2022)
17-7549213-G-T		Common variable immunodeficiency	Likely benign (Oct 15, 2020)
17-7549217-G-C		Common variable immunodeficiency	Uncertain significance (Sep 11, 2018)
17-7549221-C-T		Common variable immunodeficiency	Uncertain significance (Aug 15, 2022)
17-7549222-G-A		Common variable immunodeficiency	Likely benign (May 24, 2023)
17-7549225-C-T		Common variable immunodeficiency	Benign (Jan 31, 2024)
17-7549228-GCTGGGC-G		Common variable immunodeficiency	Uncertain significance (Feb 11, 2023)
17-7549228-G-GCTGGGC		Common variable immunodeficiency	Uncertain significance (Dec 07, 2022)
17-7549233-G-T		Common variable immunodeficiency	Uncertain significance (Dec 31, 2022)
17-7549240-C-T		Common variable immunodeficiency	Likely benign (Apr 10, 2022)
17-7549241-C-G		Common variable immunodeficiency	Uncertain significance (Mar 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNFSF12	protein_coding	protein_coding	ENST00000557233	11	12718

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.770	0.230	124514	0	15	124529	0.0000602

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.983	137	173	0.790	0.0000101	2068
Missense in Polyphen		31	55.131	0.56229		612
Synonymous	-0.330	74	70.5	1.05	0.00000413	699
Loss of Function	3.60	4	22.4	0.178	0.00000137	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000461	0.000460
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000607	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000269	0.0000269
Middle Eastern	0.0000607	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines. Promotes IL8 secretion. {ECO:0000269|PubMed:10085077, ECO:0000269|PubMed:23667509}.
• Pathway: Cytokine-cytokine receptor interaction - Homo sapiens (human);TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;TWEAK;induction of apoptosis through dr3 and dr4/5 death receptors;TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Immune System (Consensus)

Recessive Scores

• pRec: 0.504

Intolerance Scores

• loftool: 0.174
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.302
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0777

Mouse Genome Informatics

• Gene name: Tnfsf12
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: angiogenesis;positive regulation of endothelial cell proliferation;apoptotic process;immune response;signal transduction;regulation of signaling receptor activity;cell differentiation;tumor necrosis factor-mediated signaling pathway;endothelial cell migration;positive regulation of protein catabolic process;positive regulation of angiogenesis;extrinsic apoptotic signaling pathway;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: extracellular region;extracellular space;plasma membrane;integral component of plasma membrane;perinuclear region of cytoplasm
• Molecular function: signaling receptor binding;cytokine activity;tumor necrosis factor receptor binding;protein binding