TNFSF12

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

Basic information

Region (hg38): 17:7548508-7557890

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 (237 variants)
not_provided (11 variants)
not_specified (10 variants)
TNFSF12-related_disorder (9 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. These statistics are base on transcript: NM_000003809.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				61 clinvar	4 clinvar	65
missense			116 clinvar	1 clinvar		117
nonsense			5 clinvar			5
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	124	62	4

Loading clinvar variants...

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

pHI
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