TNFSF12-TNFSF13

protein-coding

TNFSF12-TNFSF13 readthrough

Gene summary

This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]

MANE transcript

N/A

Inheritance

—

ClinVar variants

U:81B:46

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr17:7,549,099-7,561,601

External References & Databases

Ensembl (ENSG00000248871)

NCBI Gene (407977)

HGNC:33537

GenCC

ClinVar (TNFSF12-TNFSF13)

Transcript & Mutation Effects

hg38 • Region Span ~12.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TNFSF12-TNFSF13 variants in ClinVar

0 Conditions Cataloged

No annotated ClinVar phenotypes.

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				41 clinvar	4 clinvar	45
missense			75 clinvar		1 clinvar	76
nonsense			4 clinvar			4
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	81	41	5	127

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172089.4	RefSeq	NP_742086.1	11	Standard
ENST00000293826.4	Ensembl	ENSP00000293826.4	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

immune response
regulation of signaling receptor activity

Molecular Function

cytokine activity
tumor necrosis factor receptor binding

Cellular Component

extracellular space
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000293826
Coding exons: 11
Length: 12503
Individuals with no LoFs: 124514
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 124529
p: 0.0000602

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.983	137	173	0.790	0.0000101	2068
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000061	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Intolerance Scores

RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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