GCM2 (Glial Cells Missing Transcription Factor 2)
Key regulator of parathyroid gland development and calcium homeostasis
Gene Information Card
| Symbol | GCM2 |
|---|---|
| Full Name | Glial Cells Missing Transcription Factor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p24.2 |
| NCBI Gene ID | 9247 ncbi.nlm.nih.gov/gene/9247 |
| Ensembl ID | ENSG00000124827 |
| UniProt ID | O75603 |
| OMIM ID | 603716 |
| HGNC ID | 4198 |
| Aliases | GCMB, hGCMb |
Description
GCM2 encodes a transcription factor essential for parathyroid gland development and maintenance. It belongs to the glial cells missing (GCM) family, characterized by a conserved N-terminal DNA-binding domain. GCM2 regulates parathyroid-specific gene expression, including parathyroid hormone (PTH) and calcium-sensing receptor (CASR). Mutations in GCM2 cause familial isolated hypoparathyroidism (FIH) and are implicated in parathyroid carcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial Isolated Hypoparathyroidism (FIH) | Loss-of-function mutations impair parathyroid gland development, leading to deficient PTH secretion and hypocalcemia. | OMIM #146200; NCBI Gene; ClinVar |
| Parathyroid Carcinoma | Somatic gain-of-function mutations (e.g., p.Tyr394Ser) enhance transcriptional activity, promoting tumorigenesis. | COSMIC; PMID: 28119430 |
| Hypoparathyroidism, Autosomal Dominant | Dominant-negative mutations disrupt GCM2 dimerization and DNA binding, reducing target gene activation. | OMIM #146200; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Parathyroid Gland | 12.5 | High |
| Thyroid Gland | 0.8 | Low |
| Kidney | 0.3 | Not detected |
| Bone Marrow | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H508 (Parathyroid) | 15.2 | High expression |
| HEK293 | 0.0 | No endogenous expression |
| MCF7 | 0.0 | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1389T>A (p.Tyr394Ser) | Missense | Somatic; rare | Gain-of-function; increases transcriptional activity in parathyroid carcinoma |
| c.70C>T (p.Arg24*) | Nonsense | Germline; rare | Loss-of-function; truncation leading to hypoparathyroidism |
| c.428G>A (p.Arg143Gln) | Missense | Germline; rare | Dominant-negative; reduces DNA binding and transactivation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg24*) cause haploinsufficiency or complete loss of GCM2 activity, leading to hypoparathyroidism.
Gain of Function (GOF)
Missense mutations (e.g., p.Tyr394Ser) enhance GCM2 transcriptional activity, associated with parathyroid carcinoma.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg143Gln) impair dimerization and DNA binding, reducing wild-type GCM2 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Parathyroid hormone synthesis
• secretion and action (KEGG hsa04928)
• Transcriptional regulation by GCM2 (Reactome R-HSA-9619483)
Protein Summary
GCM2 is a 506-amino acid transcription factor with a conserved N-terminal GCM DNA-binding domain (residues 1-150) that recognizes a specific octamer motif (5'-ATGCGGGT-3'). It forms homodimers and activates target genes such as PTH, CASR, and GATA3. The protein is predominantly nuclear and essential for parathyroid cell survival and differentiation. Mutations in the DNA-binding or transactivation domains disrupt parathyroid function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCM2 Knockout HEK293 Cell Line | EDJ-KQ6520 | Human | 9247 | Details Get a Quote |
| GCM2 Knockout HeLa Cell Line | EDJ-KQ55112 | Human | 9247 | Details Get a Quote |
| GCM2 Knockout A-549 Cell Line | EDJ-KQ63591 | Human | 9247 | Details Get a Quote |
| GCM2 Knockout HCT 116 Cell Line | EDJ-KQ72057 | Human | 9247 | Details Get a Quote |
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