MED18

protein-coding

mediator complex subunit 18, the group of Mediator complex

Gene summary

MED18 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_017638.3

Inheritance

—

ClinVar variants

U:31B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr1:28,329,002-28,335,965

External References & Databases

Ensembl (ENSG00000130772)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 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 MED18 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017638.3. 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			30 clinvar	1 clinvar		31
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	31	1	0	32

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017638.3	RefSeq	NP_060108.2	2	MANE Select
ENST00000373842.9	Ensembl	ENSP00000362948.4	2	MANE Select
NM_001127350.2	RefSeq	NP_001120822.1	2	Standard
ENST00000398997.2	Ensembl	ENSP00000381963.2	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
termination of RNA polymerase II transcription

Molecular Function

transcription coregulator activity
protein binding

Cellular Component

mediator complex
core mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373842
Coding exons: 2
Length: 6964
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125747
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.05	92	125	0.736	0.00000737	1395
Missense (PolyPhen)		28	40.57	0.69017		400
Synonymous	-0.530	47	42.6	1.10	0.00000228	398
Loss of Function	0.261	6	6.73	0.891	4.58e-7	69

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000098	0.000087	rare
Ashkenazi Jewish	0.00092	0.00089	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0.00050	0.00049	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.;

Recessive Scores

pRec: 0.128

Intolerance Scores

LoFtool: 0.511
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

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