GCM1: Glial Cells Missing Transcription Factor 1
A key regulator of placental development and trophoblast differentiation
Gene Information Card
| Symbol | GCM1 |
|---|---|
| Full Name | Glial Cells Missing Transcription Factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.1 |
| NCBI Gene ID | 8521 ncbi.nlm.nih.gov/gene/8521 |
| Ensembl ID | ENSG00000137270 |
| UniProt ID | O75616 |
| OMIM ID | 603715 |
| HGNC ID | 4197 |
| Aliases | GCMa, hGCMa |
Description
GCM1 (Glial Cells Missing Transcription Factor 1) encodes a transcription factor that is a master regulator of placental development. It is essential for the differentiation of cytotrophoblasts into syncytiotrophoblasts, fusion of trophoblast cells, and expression of placental hormones such as human chorionic gonadotropin (hCG). GCM1 binds to specific DNA sequences (GCM motifs) in target gene promoters. It is primarily expressed in the placenta and plays a critical role in branching morphogenesis of chorionic villi. Dysregulation of GCM1 is associated with pregnancy complications including preeclampsia and intrauterine growth restriction (IUGR).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Preeclampsia | Reduced GCM1 expression leads to impaired trophoblast fusion and syncytiotrophoblast formation, contributing to placental dysfunction and hypertension during pregnancy. | ClinVar, PMID: 16968736 |
| Intrauterine Growth Restriction (IUGR) | Decreased GCM1 levels are associated with abnormal placental villous development and reduced nutrient transport to the fetus. | ClinVar, PMID: 16968736 |
| Placental Insufficiency | Loss-of-function mutations or downregulation of GCM1 impair placental angiogenesis and trophoblast invasion. | ClinVar, PMID: 16968736 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 28.5 | High |
| Testis | 0.3 | Low |
| Thyroid | 0.2 | Low |
| Lung | 0.1 | Low |
| Kidney | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| BeWo (choriocarcinoma) | 15.2 | Trophoblast cell line, high expression |
| JEG-3 (choriocarcinoma) | 12.8 | Trophoblast cell line, moderate expression |
| HEK293 | 0.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.964C>T (p.Arg322Trp) | Missense | Rare | Loss of DNA-binding activity; associated with placental dysfunction |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression; likely pathogenic |
| c.1045G>A (p.Gly349Ser) | Missense | Rare | Reduced transcriptional activity; reported in IUGR |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the DNA-binding domain (e.g., p.Arg322Trp) impair target gene activation, leading to trophoblast fusion defects.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Placenta development (Reactome: R-HSA-983170)
• Transcriptional regulation by GCM1 (Reactome: R-HSA-983168)
Protein Summary
GCM1 is a 436-amino acid transcription factor containing a conserved N-terminal DNA-binding domain (GCM domain) and a C-terminal transactivation domain. It forms homodimers and binds to palindromic GCM motifs in target gene promoters. GCM1 is essential for the fusion of cytotrophoblasts into the multinucleated syncytiotrophoblast layer, which is critical for placental hormone production and nutrient exchange. The protein is predominantly nuclear in trophoblast cells. Post-translational modifications include phosphorylation, which modulates its activity. GCM1 also regulates genes involved in placental angiogenesis, such as VEGF and PGF.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCM1 Knockout HEK293 Cell Line | EDJ-KQ6268 | Human | 8521 | Details Get a Quote |
| GCM1 Knockout HeLa Cell Line | EDJ-KQ54929 | Human | 8521 | Details Get a Quote |
| GCM1 Knockout A-549 Cell Line | EDJ-KQ63415 | Human | 8521 | Details Get a Quote |
| GCM1 Knockout HCT 116 Cell Line | EDJ-KQ71879 | Human | 8521 | Details Get a Quote |
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