MED28
protein-codingmediator complex subunit 28, the group of Mediator complex
Gene summary
Predicted to enable actin binding activity. Predicted to be involved in RNA polymerase II preinitiation complex assembly; positive regulation of transcription elongation by RNA polymerase II; and positive regulation of transcription initiation by RNA polymerase II. Predicted to act upstream of or within negative regulation of smooth muscle cell differentiation and stem cell population maintenance. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MED28 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_025205.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 37 | 1 | 38 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 40 | 1 | 0 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079481.2 | 4 | MANE Select | |
| Ensembl | ENSP00000237380.6 | 4 | MANE Select | |
| Ensembl | ENSP00000426529.1 | 5 | Standard | |
| Ensembl | ENSP00000759037.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Developmental Biology
- Transcriptional regulation of white adipocyte differentiation
Biological Process
- stem cell population maintenance
- negative regulation of smooth muscle cell differentiation
Molecular Function
- actin binding
- protein binding
Cellular Component
- nucleoplasm
- membrane
- mediator complex
- cortical actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000237380
- Coding exons
- 4
- Length
- 19475
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125747
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.279 | 106 | 98.2 | 1.08 | 0.00000491 | 1144 |
| Missense (PolyPhen) | 16 | 16.485 | 0.97055 | 233 | ||
| Synonymous | -2.48 | 62 | 41.6 | 1.49 | 0.00000227 | 355 |
| Loss of Function | 0.717 | 7 | 9.37 | 0.747 | 4.65e-7 | 101 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000089 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May be part of a complex containing NF2/merlin that participates in cellular signaling to the actin cytoskeleton downstream of tyrosine kinase signaling pathways. {ECO:0000269|PubMed:15467741}.;
Recessive Scores
- pRec
- 0.166
Intolerance Scores
- LoFtool
- 0.377
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |