MYLIP (Myosin Regulatory Light Chain Interacting Protein): Gene, Function, and Clinical Significance
A comprehensive overview of the MYLIP gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | MYLIP |
|---|---|
| Full Name | Myosin regulatory light chain interacting protein |
| Gene Type | Protein coding |
| Chromosomal Location | 6p22.3 |
| NCBI Gene ID | 29116 ncbi.nlm.nih.gov/gene/29116 |
| Ensembl ID | ENSG00000007944 |
| UniProt ID | Q8WXI7 |
| OMIM ID | 607545 |
| HGNC ID | HGNC:29655 |
| Aliases | IDOL, MIR, FLJ14294 |
Description
MYLIP (myosin regulatory light chain interacting protein), also known as IDOL (inducible degrader of the LDL receptor), encodes an E3 ubiquitin ligase that regulates cholesterol homeostasis by targeting the low-density lipoprotein receptor (LDLR) for ubiquitination and degradation. It is involved in cellular lipid uptake and has been implicated in various metabolic and cardiovascular conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypercholesterolemia | MYLIP variants may affect LDLR degradation, influencing plasma LDL cholesterol levels. | ClinVar: risk allele associated with altered LDL cholesterol; PMID: 21763484 |
| Coronary artery disease | Dysregulation of LDLR degradation via MYLIP can contribute to atherosclerosis. | GWAS: MYLIP locus associated with CAD risk; PMID: 26343387 |
| Familial hypercholesterolemia (modifier) | MYLIP mutations may modify phenotype in FH patients by affecting LDLR expression. | ClinVar: variants reported in FH patients; PMID: 23375655 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Adipose tissue | 8.5 | Low |
| Skeletal muscle | 5.2 | Low |
| Brain | 3.1 | Low |
| Kidney | 2.4 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Liver cancer cell line; high expression |
| A549 | 4.3 | Lung carcinoma; moderate |
| MCF7 | 2.1 | Breast cancer; low |
| K562 | 1.0 | Leukemia; very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs9370867 | SNV (intronic) | Allele frequency ~0.30 (1000 Genomes) | Associated with LDL cholesterol levels; likely regulatory |
| rs11185316 | SNV (3' UTR) | Allele frequency ~0.15 | May affect mRNA stability; linked to lipid traits |
| c.1043C>T (p.Pro348Leu) | Missense | Rare (<0.01) | Reported in ClinVar as uncertain significance; potential effect on protein function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MYLIP would reduce LDLR degradation, leading to increased LDLR on cell surface and lower plasma LDL cholesterol. Such variants are rare and may be protective against hypercholesterolemia.
Gain of Function (GOF)
Gain-of-function mutations would enhance LDLR degradation, reducing LDL clearance and increasing plasma LDL cholesterol, predisposing to hypercholesterolemia and cardiovascular disease.
Dominant Negative (DN)
Dominant-negative mutations could interfere with the normal E3 ligase activity, potentially leading to haploinsufficiency or altered regulation of LDLR.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • zinc ion binding |
| • protein ubiquitination | • low-density lipoprotein receptor catabolic process |
| • cholesterol homeostasis | • negative regulation of low-density lipoprotein receptor activity |
Pathways
• LDL receptor degradation pathway
• Cholesterol metabolism
• Ubiquitin-proteasome pathway
Protein Summary
The MYLIP protein (IDOL) is a 445-amino acid E3 ubiquitin ligase with an N-terminal FERM domain and a C-terminal RING finger domain. It ubiquitinates the cytoplasmic tail of LDLR, marking it for proteasomal degradation. This process is induced by sterols via the liver X receptor (LXR) pathway, providing a feedback mechanism for cholesterol uptake. MYLIP is primarily expressed in liver and adipose tissue, where it regulates lipid metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MYLIP Knockout HEK293 Cell Line | EDJ-KQ8994 | Human | 29116 | Details Get a Quote |
| MYLIP Knockout A-549 Cell Line | EDJ-KQ35430 | Human | 29116 | Details Get a Quote |
| MYLIP Knockout HCT 116 Cell Line | EDJ-KQ35431 | Human | 29116 | Details Get a Quote |
| MYLIP Knockout HeLa Cell Line | EDJ-KQ35432 | Human | 29116 | Details Get a Quote |
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