| Category | Evidence summary | Key citations |
|---|---|---|
| Identity/domains | **nhr-80** in *Caenorhabditis elegans* matches the UniProt target Q8ITW8/H10E21.3 and is consistently described in the literature as an HNF4-like nuclear hormone receptor; recent work also describes it as a **C4 zinc-finger nuclear receptor**. Functionally, it belongs to the nematode-expanded NHR family and is linked to lipid-metabolic transcriptional control. | (pqac-00000000, pqac-00000003, pqac-00000005) |
| Localization/expression | NHR-80 is expressed in the **intestine**, the major fat-metabolic tissue, and localizes to the **nucleus**; in germline-less animals its mRNA/protein levels rise in intestinal cells. Palmitic acid and mTORC1 inhibition also promote intestinal nuclear localization in recent work. | (pqac-00000001, pqac-00000015, pqac-00000018, pqac-00000019, pqac-00000006) |
| Core molecular function | NHR-80 acts as a **transcription factor regulating fatty-acid desaturation/lipogenesis**, especially maintenance of monounsaturated fatty-acid production from saturated precursors. It is required for adaptive induction of Δ9 desaturase genes and can transactivate lipogenic targets downstream of mitochondrial stress. | (pqac-00000001, pqac-00000005, pqac-00000011, pqac-00000017) |
| Key downstream targets | Best-supported targets are the Δ9 desaturases **fat-5, fat-6, and fat-7**; in germline-loss longevity, **fat-6** and its oleic-acid product are especially important. Under UPRmt/citrate signaling, NHR-80 also promotes **dgat-2** and lipogenic/desaturase genes. | (pqac-00000000, pqac-00000005, pqac-00000010, pqac-00000011, pqac-00000013, pqac-00000015) |
| Key upstream regulators/inputs | Upstream inputs include **germline loss**, which induces nhr-80; **DVE-1/UBL-5-dependent mitochondrial UPR/citrate signaling**, which activates nhr-80 transcription; and **palmitic acid** plus **mTORC1 inhibition**, which promote NHR-80 nuclear localization in the FEDUS developmental program. | (pqac-00000000, pqac-00000005, pqac-00000006, pqac-00000014, pqac-00000015) |
| Binding partners | NHR-80 physically and functionally partners with **NHR-49** to activate fatty-acid desaturase genes; this partnership is a central node in lipid-homeostasis regulation. Reviews note they likely dimerize yet also retain some non-overlapping functions. | (pqac-00000002, pqac-00000004, pqac-00000008, pqac-00000010) |
| Pathways/phenotypes | Major pathways are **fatty-acid desaturation**, **germline-loss longevity**, **lysosome-to-nucleus lipid signaling**, **mitochondrial UPR-driven lipogenesis**, and **starvation-triggered early development (FEDUS)**. Phenotypes include altered fatty-acid composition, synthetic inviability when desaturation capacity is limited, mitochondrial defects, and suppression of longevity programs when nhr-80 is lost. | (pqac-00000000, pqac-00000008, pqac-00000009, pqac-00000012, pqac-00000014, pqac-00000026) |
| Ligands/metabolites | The strongest direct metabolite evidence is **oleoylethanolamide (OEA)**, increased by LIPL-4 signaling and reported to bind **NHR-80** and activate NHR-49/NHR-80 target transcription. **Oleic acid (OA)** is a critical functional product of the NHR-80/FAT-6 pathway, and **palmitic acid** acts upstream to stimulate NHR-80-dependent developmental signaling. | (pqac-00000009, pqac-00000010, pqac-00000015, pqac-00000026) |
| Quantitative data highlights | In nhr-80 mutants, **18:0 rises to 10.2 ± 0.3%** and **18:1Δ9 falls to 2.2 ± 0.1%** vs wild type **6.8 ± 0.2%** and **3.2 ± 0.1%**; triglycerides remain ~**44 ± 1% vs 45 ± 1%** in WT. In germline-less **glp-1** animals, loss of nhr-80 causes a **45% reduction in mean lifespan** (**p < 0.0001**); in **mes-1** mutants lifespan drops **21 d to 14 d** with nhr-80 RNAi. LIPL-4 overexpression increases mean lifespan by **55%**, lbp-8 transgenics by **30%**, and both effects require nhr-80; in FEDUS co-culture, ~**40%** of WT larvae develop without palmitic acid. | (pqac-00000009, pqac-00000011, pqac-00000012, pqac-00000015, pqac-00000026) |
| Recent 2023-2024 updates | 2023 reviews place NHR-80 in the conserved desaturase/membrane-fluidity module with NHR-49 and Δ9 desaturases. In 2024, palmitic acid was shown to drive **intestinal nuclear localization of NHR-80** and promote starvation-resistant developmental initiation via an NHR-49/80-peroxisome-neuron axis; parallel 2024 work on host/microbial fat-desaturation signals further strengthens the broader NHR-49-centered circuit in which NHR-80 is an established partner. | (pqac-00000006, pqac-00000020, pqac-00000023, pqac-00000024) |
| Applications/implementations | nhr-80-linked biology is used in **aging research**, **lipid-metabolism and membrane-fluidity studies**, and **nutraceutical/drug screening**. Examples include qPCR-based anti-obesity/nutraceutical assays tracking **nhr-80** expression as a lipid-signaling readout, and translational platforms coupling *C. elegans* phenotypes with **HEK293 PPARα reporter assays** for lipid-sensing molecules. | (pqac-00000025, pqac-00000026) |


*Table: This table summarizes experimentally supported functional annotation for *C. elegans* nhr-80 (UniProt Q8ITW8), including identity, localization, molecular role, pathways, quantitative findings, and recent updates. It is useful as a compact evidence map for gene-function reporting and downstream annotation work.*