TNFSF12 TNF superfamily member 12 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TNFSF12provided by HGNC
Official Full Name: TNF superfamily member 12provided by HGNC
Primary source: HGNC:HGNC:11927
See related: Ensembl:ENSG00000239697 MIM:602695; AllianceGenome:HGNC:11927
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APO3L; DR3LG; TWEAK; TNLG4A
Summary: The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]
Expression: Ubiquitous expression in fat (RPKM 27.5), lung (RPKM 20.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p13.1

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (7549058..7557881)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (7453339..7462142)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (7452375..7461198)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-alpha in older adults: A case-control study.
Title: Sarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in older adults: A case-control study.
TWEAK and Fn14 are overexpressed in immune-mediated necrotizing myopathy: implications for muscle damage and repair.
Title: TWEAK and Fn14 are overexpressed in immune-mediated necrotizing myopathy: implications for muscle damage and repair.
Sclerostin and TNF-related weak inducer of apoptosis: can they be important in the patients with glomerulonephritis?
Title: Sclerostin and TNF-related weak inducer of apoptosis: can they be important in the patients with glomerulonephritis?
Relief of Extracellular Matrix Deposition Repression by Downregulation of IRF1-Mediated TWEAK/Fn14 Signaling in Keloids.
Title: Relief of Extracellular Matrix Deposition Repression by Downregulation of IRF1-Mediated TWEAK/Fn14 Signaling in Keloids.
TWEAK/Fn14 signaling may function as a reactive compensatory mechanism against extracellular matrix accumulation in keloid fibroblasts.
Title: TWEAK/Fn14 signaling may function as a reactive compensatory mechanism against extracellular matrix accumulation in keloid fibroblasts.
Status of TWEAK DNA methylation and mRNA expression in systemic lupus erythematosus.
Title: Status of TWEAK DNA methylation and mRNA expression in systemic lupus erythematosus.
TWEAK-Fn14 Axis Induces Calcium-Associated Autophagy and Cell Death To Control Mycobacterial Survival in Macrophages.
Title: TWEAK-Fn14 Axis Induces Calcium-Associated Autophagy and Cell Death To Control Mycobacterial Survival in Macrophages.
TWEAK and TNFalpha, Both TNF Ligand Family Members and Multiple Sclerosis-Related Cytokines, Induce Distinct Gene Response in Human Brain Microvascular Endothelial Cells.
Title: TWEAK and TNFα, Both TNF Ligand Family Members and Multiple Sclerosis-Related Cytokines, Induce Distinct Gene Response in Human Brain Microvascular Endothelial Cells.
Can plasma TWEAK levels predict coronary slow flow in patients with chronic kidney disease?
Title: Can plasma TWEAK levels predict coronary slow flow in patients with chronic kidney disease?
Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for gamma-secretase activity.
Title: Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for γ-secretase activity.

Submit: New GeneRIF Correction See all GeneRIFs (214)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:484141

TNFSF12_268.2 (e-PCR)
- UniSTS:277833

RH98958 (e-PCR)
- UniSTS:85338

Readthrough TNFSF12-TNFSF13

Readthrough gene: TNFSF12-TNFSF13, Included gene: TNFSF13

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor ligand activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed
enables tumor necrosis factor receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell migration	TAS Traceable Author Statement more info	PubMed
involved_in extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of angiogenesis	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of endothelial cell proliferation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tumor necrosis factor ligand superfamily member 12

Names: APO3 ligand; APO3/DR3 ligand; TNF-related WEAK inducer of apoptosis; tumor necrosis factor (ligand) superfamily, member 12; tumor necrosis factor ligand 4A; tumor necrosis factor superfamily member 12

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052944.1 RefSeqGene

Range

5001..13824

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1320

mRNA and Protein(s)

NM_003809.3 → NP_003800.1 tumor necrosis factor ligand superfamily member 12 proprotein

See identical proteins and their annotated locations for NP_003800.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript but encodes the functional protein.

Source sequence(s)

AF030099, AI091441, BC104420

Consensus CDS

CCDS11109.1

UniProtKB/Swiss-Prot

O43508, Q8IZK7, Q8WUZ7

UniProtKB/TrEMBL

A0A8V8TP82, Q4ACW9

Related

ENSP00000293825.6, ENST00000293825.11

Conserved Domains (1) summary

smart00207
Location:131 → 248

TNF; Tumour necrosis factor family

RNA

NR_037146.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) includes an additional exon in the central region, compared to variant 1. This variant is represented as non-coding because the use of the supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC019047

Related

ENST00000322272.11