MED8

protein-coding

mediator complex subunit 8, the group of Mediator complex

Gene summary

This gene encodes a protein component of the mediator complex, which aids in transcriptional activation through interaction with RNA polymerase II and gene-specific transcription factors. The encoded protein may also function in ubiquitin ligation and protein degradation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

MANE transcript

NM_201542.5

Inheritance

—

ClinVar variants

U:25

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr1:43,383,917-43,389,808

External References & Databases

Ensembl (ENSG00000159479)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb

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GenCC 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 MED8 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_201542.5. 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			22 clinvar			22
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	25	0	0	25

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_201542.5	RefSeq	NP_963836.2	7	MANE Select
ENST00000372457.9	Ensembl	ENSP00000361535.4	7	MANE Select
NM_001001653.3	RefSeq	NP_001001653.1	5	Standard
NM_052877.5	RefSeq	NP_443109.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Herpes simplex infection - 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 initiation from RNA polymerase II promoter
protein ubiquitination

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
transcription coregulator activity
protein binding

Cellular Component

nucleoplasm
mediator complex
core mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290663
Coding exons: 8
Length: 5892
Individuals with no LoFs: 125546
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125593
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.970	130	165	0.787	0.00000906	1939
Missense (PolyPhen)		35	52.347	0.66862		620
Synonymous	1.40	47	60.9	0.772	0.00000309	596
Loss of Function	1.27	11	16.6	0.664	8.79e-7	181

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00083	0.00082	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

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 play a role as a target recruitment subunit in E3 ubiquitin-protein ligase complexes and thus in ubiquitination and subsequent proteasomal degradation of target proteins.;

Recessive Scores

pRec: 0.0898

Intolerance Scores

LoFtool: 0.266
RVIS EVS: -0.21
RVIS percentile EVS: 38.58

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.778

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium