MED13

mediator complex subunit 13, the group of Mediator complex

Basic information

Region (hg38): 17:61942605-62065278

Previous symbols: [ "THRAP1" ]

Links

ENSG00000108510 ∙ NCBI:9969 ∙ OMIM:603808 ∙ HGNC:22474 ∙ Uniprot:Q9UHV7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder 61 (Definitive), mode of inheritance: AD
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual developmental disorder 61 (Strong), mode of inheritance: AD
• intellectual developmental disorder 61 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual developmental disorder 61 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 61	AD	General	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	29740699

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MED13 gene.

• not_provided (256 variants)
• Inborn_genetic_diseases (220 variants)
• Intellectual_developmental_disorder_61 (100 variants)
• MED13-related_disorder (59 variants)
• not_specified (10 variants)
• See_cases (4 variants)
• Autosomal_dominant_isolated_somatotropin_deficiency (3 variants)
• Neurodevelopmental_disorder (2 variants)
• Autism_spectrum_disorder (2 variants)
• Intellectual_disability (2 variants)
• MED13-related_neurodevelopmental_disorder (1 variants)
• CDK8-kinase_module-associated_disorder (1 variants)
• Intellectual_disability,_autosomal_dominant_13 (1 variants)
• MED13-associated_disorder (1 variants)
• Developmental_disorder (1 variants)
• Autistic_behavior (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED13 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005121.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	33	7	43
missense	2	12	364	83	6	467
nonsense	12	5	2			19
start loss						0
frameshift	12	10	1			23
splice donor/acceptor (+/-2bp)	9	2				11
Total	35	29	370	116	13

Highest pathogenic variant AF is 0.00000137905

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MED13	protein_coding	protein_coding	ENST00000397786	30	122678

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.84e-16	124782	0	3	124785	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.62	871	1.12e+3	0.779	0.0000556	14195
Missense in Polyphen		314	529.75	0.59273		6708
Synonymous	-1.38	422	388	1.09	0.0000191	4248
Loss of Function	9.19	0	98.4	0.00	0.00000492	1257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.00000886	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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. {ECO:0000269|PubMed:16595664}.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Developmental Biology;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Transcriptional regulation of white adipocyte differentiation (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.0136
• rvis_EVS: -1.43
• rvis_percentile_EVS: 4.05

Haploinsufficiency Scores

• pHI: 0.546
• hipred: Y
• hipred_score: 0.777
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.692

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Med13
• Phenotype: liver/biliary system phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: med13b
• Affected structure: cranial neural crest cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;intracellular steroid hormone receptor signaling pathway;androgen receptor signaling pathway;cholesterol homeostasis;negative regulation of DNA-binding transcription factor activity;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;triglyceride homeostasis
• Cellular component: nucleus;nucleoplasm;membrane;mediator complex
• Molecular function: transcription coregulator activity;transcription coactivator activity;nuclear receptor transcription coactivator activity;signaling receptor activity;vitamin D receptor binding;thyroid hormone receptor binding