MED12 Gene - Mediator Complex Subunit 12
MED12: A key regulator of transcription and its role in developmental disorders and cancer
Gene Information Card
| Symbol | MED12 |
|---|---|
| Full Name | Mediator Complex Subunit 12 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq13.1 |
| NCBI Gene ID | 9968 ncbi.nlm.nih.gov/gene/9968 |
| Ensembl ID | ENSG00000184634 |
| UniProt ID | Q93074 |
| OMIM ID | 300188 |
| HGNC ID | 11978 |
| Aliases | HOPA, OPA1, TRAP230, ARC240, CAGH45, TNRC11, MED12S |
Description
MED12 encodes a component of the Mediator complex, a multiprotein complex that acts as a bridge between transcription factors and RNA polymerase II. MED12 is involved in transcriptional regulation, cell growth, and development. Mutations in MED12 are associated with X-linked intellectual disability syndromes (FG syndrome, Lujan syndrome) and somatic mutations are frequently found in uterine leiomyomas and breast cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| FG syndrome (FGS1) | Loss-of-function or hypomorphic mutations in MED12 disrupt Mediator complex function, leading to impaired transcriptional regulation during development. | OMIM #305450; ClinVar |
| Lujan syndrome (LNS) | Missense mutations (e.g., p.Asn1007Ser) alter MED12 interaction with other Mediator subunits, affecting neuronal gene expression. | OMIM #309520; ClinVar |
| Uterine leiomyoma | Somatic hotspot mutations (e.g., p.Gly44Asp) in MED12 exon 2 are gain-of-function or alter Mediator complex activity, promoting tumor growth. | COSMIC; ClinVar; PMID: 21795666 |
| Breast cancer | Somatic mutations in MED12 (including exon 2) are recurrent in fibroepithelial tumors and some breast cancers, suggesting a role in tumorigenesis. | COSMIC; PMID: 25670082 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 10.5 | Medium |
| Kidney | 11.3 | Medium |
| Lung | 9.7 | Low |
| Ovary | 13.1 | Medium |
| Uterus | 14.5 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.2 | High expression |
| HeLa | 15.6 | Medium expression |
| MCF7 | 14.1 | Medium expression |
| K562 | 12.3 | Medium expression |
| HepG2 | 11.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.131G>A (p.Gly44Asp) | Missense | ~70% in uterine leiomyoma | Gain-of-function; alters Mediator complex activity |
| c.100G>A (p.Gly34Glu) | Missense | <5% in uterine leiomyoma | Likely gain-of-function |
| c.3020A>G (p.Asn1007Ser) | Missense | Rare; Lujan syndrome | Loss-of-function; disrupts Mediator function |
| c.2881C>T (p.Arg961Trp) | Missense | Rare; FG syndrome | Loss-of-function; impairs transcription |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the C-terminal region (e.g., p.Asn1007Ser, p.Arg961Trp) impair Mediator complex assembly and transcriptional activation, leading to X-linked intellectual disability syndromes.
Gain of Function (GOF)
Hotspot mutations in exon 2 (e.g., p.Gly44Asp) in uterine leiomyoma are considered gain-of-function, enhancing Mediator activity and promoting cell proliferation.
Dominant Negative (DN)
Some MED12 mutations may act in a dominant-negative manner by disrupting the Mediator complex, but specific evidence is limited; further studies are needed.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mediator complex (Reactome: R-HSA-212436)
• Transcription by RNA polymerase II (Reactome: R-HSA-73857)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
MED12 is a 2,177-amino acid protein (UniProt Q93074) that serves as a subunit of the Mediator complex. It contains a leucine-rich region and a conserved C-terminal domain. MED12 interacts with other Mediator subunits (e.g., MED13, Cyclin C-CDK8) to regulate transcription. The protein is ubiquitously expressed and plays critical roles in development, cell cycle control, and signal transduction. Mutations in MED12 are linked to neurodevelopmental disorders and various cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MED12L Knockout HEK293 Cell Line | EDJ-KQ7585 | Human | 116931 | Details Get a Quote |
| MED12L Knockout HCT 116 Cell Line | EDJ-KQ32911 | Human | 116931 | Details Get a Quote |
| MED12L Knockout HeLa Cell Line | EDJ-KQ57999 | Human | 116931 | Details Get a Quote |
| MED12L Knockout A-549 Cell Line | EDJ-KQ66486 | Human | 116931 | Details Get a Quote |
| MED12 (p.R18G) Point Mutation in HAP1 Cell Line | EDC03539 | Human | 9968 | Details Get a Quote |
| MED12 (c.6408+53C>T )Point Mutation in HAP1 Cell Line | EDC03540 | Human | 9968 | Details Get a Quote |
