ARMC5 Gene: Structure, Function, and Clinical Significance in Primary Bilateral Macronodular Adrenal Hyperplasia
A comprehensive overview of the ARMC5 gene, its protein product, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | ARMC5 |
|---|---|
| Full Name | Armadillo repeat containing 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 79798 ncbi.nlm.nih.gov/gene/79798 |
| Ensembl ID | ENSG00000140678 |
| UniProt ID | Q8N9Z9 |
| OMIM ID | 615923 |
| HGNC ID | 25789 |
| Aliases | FLJ20241, MGC126851, MGC126853 |
Description
The ARMC5 gene encodes a protein containing armadillo repeats, which are involved in protein-protein interactions. ARMC5 is a putative tumor suppressor gene, most notably associated with primary bilateral macronodular adrenal hyperplasia (PBMAH), a condition characterized by bilateral adrenal enlargement and cortisol excess. Somatic and germline mutations in ARMC5 are frequently found in PBMAH, leading to loss of function and dysregulation of adrenal cell proliferation and steroidogenesis. The protein is localized in the cytoplasm and may play a role in apoptosis and cell cycle regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary bilateral macronodular adrenal hyperplasia (PBMAH) | Inactivating mutations (germline and somatic) lead to loss of tumor suppressor function, causing adrenal hyperplasia and cortisol overproduction. | Multiple studies, including those in OMIM (615923) and ClinVar, report ARMC5 mutations in 20-50% of PBMAH cases. |
| Adrenocortical adenoma | Somatic ARMC5 mutations contribute to tumorigenesis in a subset of sporadic adrenocortical adenomas, though less frequent than in PBMAH. | COSMIC database lists ARMC5 mutations in adrenal tumors; ClinVar also includes pathogenic variants. |
| Cushing syndrome | ARMC5 mutations cause ACTH-independent Cushing syndrome due to bilateral adrenal hyperplasia and cortisol hypersecretion. | Clinical evidence from case reports and cohort studies, as referenced in OMIM and PubMed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | High | High expression in adrenal cortex, consistent with its role in adrenal function. |
| Thyroid | Medium | Moderate expression; relevance not fully characterized. |
| Kidney | Medium | Moderate expression; possible role in renal tissues. |
| Liver | Low | Low expression; minimal functional data. |
| Brain | Low | Low expression; not well studied. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| H295R (adrenocortical carcinoma) | High | Adrenal cell line; used for functional studies of ARMC5. |
| SW13 (adrenal carcinoma) | Medium | Adrenal origin; expression lower than H295R. |
| HeLa (cervical cancer) | Low | Non-adrenal; low expression. |
| HEK293 (embryonic kidney) | Low | Common lab cell line; low endogenous expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1540C>T (p.Arg514Ter) | Nonsense | Reported in PBMAH; loss of function | Pathogenic; truncating mutation leading to protein loss. |
| c.1960C>T (p.Arg654Ter) | Nonsense | Reported in PBMAH; loss of function | Pathogenic; truncating mutation. |
| c.2578C>T (p.Arg860Ter) | Nonsense | Reported in PBMAH; loss of function | Pathogenic; truncating mutation. |
| c.1061G>A (p.Trp354Ter) | Nonsense | Reported in PBMAH; loss of function | Pathogenic; truncating mutation. |
| c.2266C>T (p.Arg756Cys) | Missense | Reported in PBMAH; likely loss of function | Uncertain significance; functional studies suggest impaired activity. |
Mutation functional classification
Loss of Function (LOF)
Most ARMC5 mutations are inactivating (nonsense, frameshift, splice-site) leading to haploinsufficiency or complete loss of protein function, consistent with tumor suppressor activity.
Gain of Function (GOF)
No evidence of gain-of-function mutations; ARMC5 acts as a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type protein function, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • cytoplasm |
| • apoptotic process | • cell proliferation |
| • negative regulation of cell population proliferation | • adrenal gland development |
Pathways
• p53 signaling pathway (indirectly via apoptosis regulation)
• cAMP signaling pathway (in adrenal steroidogenesis)
• Cell cycle regulation
Protein Summary
The ARMC5 protein contains armadillo repeats, which are alpha-helical motifs that mediate protein-protein interactions. It is localized in the cytoplasm and is involved in regulating apoptosis and cell proliferation. In adrenal cortex, ARMC5 acts as a tumor suppressor, and its loss leads to abnormal cell growth and cortisol production. The protein may also interact with other proteins to modulate steroidogenic gene expression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARMC5 Knockout HEK293 Cell Line | EDJ-KQ2196 | Human | 79798 | Details Get a Quote |
| ARMC5 Knockout A-549 Cell Line | EDJ-KQ22428 | Human | 79798 | Details Get a Quote |
| ARMC5 Knockout HCT 116 Cell Line | EDJ-KQ22429 | Human | 79798 | Details Get a Quote |
| ARMC5 Knockout HeLa Cell Line | EDJ-KQ22430 | Human | 79798 | Details Get a Quote |
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