NCOA4
Nuclear Receptor Coactivator 4
Gene Information Card
| Symbol | NCOA4 |
|---|---|
| Full Name | Nuclear Receptor Coactivator 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q11.22 |
| NCBI Gene ID | 8031 ncbi.nlm.nih.gov/gene/8031 |
| Ensembl ID | ENSG00000165630 |
| UniProt ID | Q13772 |
| OMIM ID | 601984 |
| HGNC ID | 7671 |
| Aliases | ARA70, ELE1, PTC3, RFG, TCO |
Description
NCOA4 (Nuclear Receptor Coactivator 4) encodes a protein that functions as a coactivator of nuclear receptors, including androgen receptor. It also acts as a selective autophagy receptor for ferritin (ferritinophagy), mediating the delivery of ferritin to lysosomes for degradation, thereby regulating intracellular iron levels. NCOA4 is involved in thyroid cancer through chromosomal rearrangements (e.g., RET/PTC3) and has roles in cellular iron homeostasis, oxidative stress response, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Thyroid carcinoma (papillary) | RET/PTC3 fusion (NCOA4-RET) leads to constitutive RET kinase activation, driving oncogenesis. | PMID: 7906866, COSMIC |
| Prostate cancer | NCOA4 coactivates androgen receptor; overexpression may promote androgen-independent growth. | PMID: 10521347 |
| Iron overload disorders | Dysregulation of NCOA4-mediated ferritinophagy alters iron homeostasis, contributing to cellular iron accumulation. | PMID: 24695223 |
| Neurodegeneration (Alzheimer's, Parkinson's) | Impaired ferritinophagy leads to iron dyshomeostasis and oxidative stress in neurons. | PMID: 31006538 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Liver | 10.2 | Medium |
| Thyroid | 8.9 | Medium |
| Testis | 7.6 | Low |
| Brain | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.1 | Cervical cancer cell line |
| HepG2 | 11.8 | Hepatocellular carcinoma |
| K562 | 9.4 | Chronic myeloid leukemia |
| MCF7 | 8.2 | Breast cancer |
| PC3 | 7.5 | Prostate cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| NCOA4-RET fusion (PTC3) | Chromosomal rearrangement | Common in radiation-induced papillary thyroid carcinoma | Constitutive RET kinase activation |
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of function |
| c.1234C>T (p.Arg412Trp) | Missense | Rare | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Loss of ferritinophagy leads to iron accumulation and oxidative stress.
Gain of Function (GOF)
NCOA4-RET fusions result in constitutive RET signaling, promoting cell proliferation.
Dominant Negative (DN)
Not well characterized; potential interference with wild-type NCOA4 in autophagy.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Autophagy - ferritinophagy (hsa04140)
• Thyroid cancer signaling (hsa05216)
• RET signaling (hsa04010)
Protein Summary
NCOA4 is a 614-amino acid protein (UniProt Q13772) that contains a nuclear receptor interaction domain and a coiled-coil region. It functions as a coactivator for nuclear receptors, particularly androgen receptor, and as a selective autophagy receptor for ferritin (FTH1/FTL). Through its interaction with LC3 and ferritin, NCOA4 mediates ferritinophagy, releasing free iron for cellular use. The protein is localized to the cytoplasm and nucleus, and its dysregulation is implicated in cancer and iron-related disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCOA4 Knockout HEK293 Cell Line | EDJ-KQ985 | Human | 8031 | Details Get a Quote |
| NCOA4 Knockout HeLa Cell Line | EDJ-KQ20010 | Human | 8031 | Details Get a Quote |
| NCOA4 Knockout HCT 116 Cell Line | EDJ-KQ18690 | Human | 8031 | Details Get a Quote |
| NCOA4 Knockout BEAS-2B Cell Line | EDJ-KZ36 | Human | 8031 | Details Get a Quote |
| NCOA4 Knockout A-549 Cell Line | EDJ-KQ63305 | Human | 8031 | Details Get a Quote |
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