MED11

protein-coding

mediator complex subunit 11, the group of Mediator complex

Gene summary

MED11 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II (Sato et al., 2003 [PubMed 12584197]).[supplied by OMIM, Oct 2008]

MANE transcript

NM_001001683.4

Inheritance

ClinVar variants

P:2U:19

Top phenotype

Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities

gnomAD constraint

pLI —, LoF o/e 1.52

Max pathogenic AF

—

Genomic locus

chr17:4,731,428-4,733,608

External References & Databases

Ensembl (ENSG00000161920)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957225

Submitter: Labcorp Genetics (formerly Invitae)

neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957225

Submitter: PanelApp Australia

neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalitiesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957225

Submitter: G2P

neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalitiesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957225

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalitiesAR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 36001086

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MED11 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 18

Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalitiesTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001001683.4. 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						0
missense			19 clinvar			19
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	1	1	19	0	0	21

Highest pathogenic variant AF is 0.000014250292

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001001683.4	RefSeq	NP_001001683.1	3	MANE Select
ENST00000293777.6	Ensembl	ENSP00000293777.5	3	MANE Select
NM_001305000.2	RefSeq	NP_001291929.1	3	Standard
ENST00000573708.1	Ensembl	ENSP00000459834.1	2	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

regulation of transcription by RNA polymerase II
protein ubiquitination

Molecular Function

transcription coregulator activity
protein binding
ubiquitin protein ligase activity

Cellular Component

ubiquitin ligase complex
mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000293777
Coding exons: 3
Length: 2183
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125747
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.646	54	69.1	0.781	0.00000337	740
Missense (PolyPhen)		17	16.911	1.0053		201
Synonymous	-0.812	34	28.5	1.19	0.00000137	244
Loss of Function	-1.17	9	5.92	1.52	3.35e-7	62

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0014	0.0014	notable
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: 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.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.605
RVIS EVS: 0.01
RVIS percentile EVS: 54.63

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

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