MED4
protein-codingmediator complex subunit 4, the group of Mediator complex
Gene summary
This gene encodes a component of the Mediator complex. The Mediator complex interacts with DNA-binding gene-specific transcription factors to modulate transcription by RNA polymerase II. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
- VDRIP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~41.8 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 MED4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014166.4. 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 | 3 | 3 | ||||
| missense | 29 | 1 | 30 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 38 | 0 | 1 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054885.1 | 7 | MANE Select | |
| Ensembl | ENSP00000258648.2 | 7 | MANE Select | |
| RefSeq | NP_001257558.1 | 6 | Standard | |
| Ensembl | ENSP00000367849.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thyroid hormone signaling pathway - Homo sapiens (human)
- Developmental Biology
- Gene expression (Transcription)
- Generic Transcription Pathway
- RNA Polymerase II Transcription
Biological Process
- regulation of transcription by RNA polymerase II
- transcription by RNA polymerase II
- transcription initiation from RNA polymerase II promoter
- intracellular steroid hormone receptor signaling pathway
- androgen receptor signaling pathway
Molecular Function
- transcription coregulator activity
- protein binding
- nuclear receptor transcription coactivator activity
- signaling receptor activity
- vitamin D receptor binding
Cellular Component
- nucleus
- nucleoplasm
- membrane
- mediator complex
- core mediator complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000258648
- Coding exons
- 7
- Length
- 41809
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125746
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.02 | 104 | 138 | 0.756 | 0.00000641 | 1756 |
| Missense (PolyPhen) | 25 | 48.237 | 0.51827 | 632 | ||
| Synonymous | -1.10 | 61 | 51.0 | 1.20 | 0.00000250 | 485 |
| Loss of Function | 2.16 | 6 | 15.0 | 0.399 | 7.28e-7 | 185 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
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.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.311
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 75.12
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |