GRAMD1C Gene: Structure, Function, and Clinical Relevance
A comprehensive biomedical overview of GRAMD1C, a lipid transfer protein implicated in cholesterol homeostasis and cancer.
Gene Information Card
| Symbol | GRAMD1C |
|---|---|
| Full Name | GRAM domain containing 1C |
| Gene Type | protein-coding |
| Chromosomal Location | 3q25.33 |
| NCBI Gene ID | 54762 ncbi.nlm.nih.gov/gene/54762 |
| Ensembl ID | ENSG00000114023 |
| UniProt ID | Q5VWZ1 |
| OMIM ID | 616550 |
| HGNC ID | 26008 |
| Aliases | GRAMD1C, DKFZp686K23112, FLJ14700 |
Description
GRAMD1C encodes a protein containing a GRAM domain, which is involved in lipid binding and membrane trafficking. It functions as a lipid transfer protein, specifically mediating the transport of cholesterol and phosphatidylserine between membranes. GRAMD1C is part of the GRAMD1 family and is implicated in cellular cholesterol homeostasis, autophagy, and potentially in cancer progression. Its expression is regulated by sterol regulatory element-binding proteins (SREBPs) and it localizes to the endoplasmic reticulum and plasma membrane contact sites.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered expression and mutations may affect cholesterol metabolism and signaling pathways, promoting tumor growth. | COSMIC and literature reports indicate somatic mutations and differential expression in multiple cancer types. |
| Cholesterol metabolism disorders | Defects in lipid transfer function could disrupt cellular cholesterol distribution, contributing to metabolic dysregulation. | Inferred from functional studies; no direct OMIM disease association yet. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.3 | Low |
| Brain | 8.5 | Low |
| Breast | 15.2 | Medium |
| Colon | 10.1 | Low |
| Kidney | 9.8 | Low |
| Liver | 7.4 | Low |
| Lung | 11.6 | Low |
| Muscle | 6.2 | Low |
| Ovary | 13.4 | Medium |
| Pancreas | 8.9 | Low |
| Prostate | 14.7 | Medium |
| Skin | 12.0 | Low |
| Small intestine | 9.3 | Low |
| Spleen | 7.8 | Low |
| Stomach | 10.5 | Low |
| Testis | 16.8 | Medium |
| Thyroid | 11.2 | Low |
| Uterus | 12.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 18.5 | Moderate expression |
| MCF7 (breast cancer) | 22.3 | High expression |
| HepG2 (liver cancer) | 14.2 | Moderate expression |
| HeLa (cervical cancer) | 16.7 | Moderate expression |
| K562 (leukemia) | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.01% (COSMIC) | Unknown; predicted benign |
| c.567C>T (p.Pro189Leu) | Missense | 0.02% (COSMIC) | Unknown; may affect protein stability |
| c.890_891insA (p.Leu297fs) | Frameshift | 0.005% (COSMIC) | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the GRAM domain are likely to impair lipid transfer activity, leading to altered cholesterol homeostasis.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression in some cancers may contribute to tumor progression.
Dominant Negative (DN)
No evidence for dominant-negative effects; GRAMD1C likely functions as a monomer or homodimer, but dominant-negative mutations have not been characterized.
View complete mutation data：
Gene Ontology (GO)
| • lipid binding | • phosphatidylserine binding |
| • cholesterol binding | • membrane |
| • endoplasmic reticulum | • plasma membrane |
| • lipid transport | • cholesterol transport |
| • cellular response to sterol |
Pathways
• Cholesterol metabolism
• Lipid transport
• Autophagy
• SREBP signaling
Protein Summary
GRAMD1C is a 657-amino acid protein with a GRAM domain at the N-terminus and a transmembrane domain. It localizes to the endoplasmic reticulum and plasma membrane contact sites, where it facilitates the transfer of cholesterol and phosphatidylserine. The protein is involved in maintaining cellular cholesterol homeostasis and has been implicated in autophagy and cancer. Its expression is regulated by SREBPs, and it interacts with other lipid transfer proteins. Structural studies suggest it forms a homodimer and undergoes conformational changes upon lipid binding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRAMD1C Knockout HEK293 Cell Line | EDJ-KQ13678 | Human | 54762 | Details Get a Quote |
| GRAMD1C Knockout A-549 Cell Line | EDJ-KQ43375 | Human | 54762 | Details Get a Quote |
| GRAMD1C Knockout HCT 116 Cell Line | EDJ-KQ43376 | Human | 54762 | Details Get a Quote |
| GRAMD1C Knockout HeLa Cell Line | EDJ-KQ43377 | Human | 54762 | Details Get a Quote |
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