TNFSF11
TNF superfamily member 11 | CD254, ODF, OPGL, RANKL, TRANCE

This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dendritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. [provided by RefSeq, Mar 2026]

Developmental clusters: GC5
Biological processes 52 terms
calcium-mediated signaling (GO:0019722)calcium-mediated signaling (GO:0019722)cell communication (GO:0007154)cell surface receptor signaling pathway (GO:0007166)cytokine activity (GO:0005125)cytokine activity (GO:0005125)cytokine activity (GO:0005125)cytokine-mediated signaling pathway (GO:0019221)cytoplasm (GO:0005737)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)identical protein binding (GO:0042802)immune response (GO:0006955)immune response (GO:0006955)membrane (GO:0016020)monocyte chemotaxis (GO:0002548)negative regulation of transcription by RNA polymerase II (GO:0000122)osteoclast differentiation (GO:0030316)osteoclast differentiation (GO:0030316)osteoclast differentiation (GO:0030316)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)positive regulation of ERK1 and ERK2 cascade (GO:0070374)positive regulation of MAPK cascade (GO:0043410)positive regulation of T cell activation (GO:0050870)positive regulation of bone resorption (GO:0045780)positive regulation of canonical NF-kappaB signal transduction (GO:0043123)positive regulation of canonical NF-kappaB signal transduction (GO:0043123)positive regulation of corticotropin-releasing hormone secretion (GO:0051466)positive regulation of corticotropin-releasing hormone secretion (GO:0051466)positive regulation of extrinsic apoptotic signaling pathway (GO:2001238)positive regulation of fever generation by positive regulation of prostaglandin secretion (GO:0071812)positive regulation of fever generation by positive regulation of prostaglandin secretion (GO:0071812)positive regulation of homotypic cell-cell adhesion (GO:0034112)positive regulation of intracellular signal transduction (GO:1902533)positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)positive regulation of osteoclast differentiation (GO:0045672)positive regulation of osteoclast differentiation (GO:0045672)positive regulation of osteoclast differentiation (GO:0045672)positive regulation of transcription by RNA polymerase II (GO:0045944)protein binding (GO:0005515)receptor ligand activity (GO:0048018)signaling (GO:0023052)signaling receptor binding (GO:0005102)tumor necrosis factor receptor binding (GO:0005164)tumor necrosis factor receptor binding (GO:0005164)tumor necrosis factor receptor superfamily binding (GO:0032813)tumor necrosis factor-mediated signaling pathway (GO:0033209)tumor necrosis factor-mediated signaling pathway (GO:0033209)
Expression (TPM)
TNFSF11 — as a Regulated Gene

TFs regulating TNFSF11 0 TFs

Transcription factors with Perturb-seq knockdown data for TNFSF11. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = TNFSF11 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to TNFSF11

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of TNFSF11, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr13:42,573,950–42,575,292 162 bp At TSS Multiome 287
chr13:42,592,966–42,593,984 19.4 kb Distal (>10kb) Multiome 117

Genome Browser

Genomic view of the TNFSF11 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr13:42,563,950 – 42,603,984
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq