MED23

mediator complex subunit 23, the group of Mediator complex

Basic information

Region (hg38): 6:131573965-131628242

Previous symbols: [ "CRSP3", "MRT18" ]

Links

ENSG00000112282 ∙ NCBI:9439 ∙ OMIM:605042 ∙ HGNC:2372 ∙ Uniprot:Q9ULK4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 18 (Limited), mode of inheritance: AR
• intellectual disability, autosomal recessive 18 (Moderate), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 18 (Strong), mode of inheritance: AR
• syndromic intellectual disability (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy	AR	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	Neurologic	21868677; 27311965; 27457812; 30847200; 31164858
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection (eg, ketogenic diet has been described as beneficial)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MED23 gene.

• Arginase deficiency (401 variants)
• not provided (97 variants)
• Inborn genetic diseases (96 variants)
• not specified (30 variants)
• Intellectual disability, autosomal recessive 18 (23 variants)
• MED23-related condition (2 variants)
• Intellectual disability (2 variants)
• ARG1-related condition (1 variants)
• Neurodevelopmental disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED23 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	38	2	42
missense	1	4	71			76
nonsense	2	4	1			7
start loss						0
frameshift	1	3	2			6
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	1	1			3
splice region		1	7	3	1	12
non coding	45	48	127	172	14	406
Total	50	60	206	210	16

Highest pathogenic variant AF is 0.0000197

Variants in MED23

This is a list of pathogenic ClinVar variants found in the MED23 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-131576370-G-A			Likely benign (Apr 08, 2021)
6-131576645-T-A		Arginase deficiency	Uncertain significance (May 24, 2022)
6-131576645-T-C		Arginase deficiency	Uncertain significance (Jun 19, 2022)
6-131576646-A-G		Arginase deficiency	Likely benign (Aug 15, 2022)
6-131576646-A-T		Arginase deficiency	Likely benign (Nov 23, 2021)
6-131576646-ATTT-A		Arginase deficiency	Likely benign (Oct 28, 2022)
6-131576647-T-C		Arginase deficiency	Likely benign (Jul 13, 2023)
6-131576655-T-C		Arginase deficiency	Uncertain significance (Aug 19, 2022)
6-131576661-A-C		Arginase deficiency	Likely pathogenic (Feb 02, 2018)
6-131576661-A-T		Arginase deficiency	Likely pathogenic (Dec 17, 2022)
6-131576664-C-T		Arginase deficiency	Uncertain significance (Sep 01, 2021)
6-131576666-C-G		Arginase deficiency • not specified	Uncertain significance (Mar 18, 2024)
6-131576666-C-T		Arginase deficiency • Inborn genetic diseases	Pathogenic (Nov 02, 2023)
6-131576667-G-A		Arginase deficiency	Conflicting classifications of pathogenicity (Oct 17, 2022)
6-131576668-A-G		Arginase deficiency	Likely benign (Oct 16, 2023)
6-131576671-A-AG		Arginase deficiency	Likely pathogenic (Dec 17, 2022)
6-131576672-G-T		Arginase deficiency	Uncertain significance (Mar 11, 2022)
6-131576674-G-A		Arginase deficiency	Likely benign (Jan 26, 2022)
6-131576675-G-C		Arginase deficiency	Uncertain significance (Feb 03, 2022)
6-131576680-A-C		Arginase deficiency	Conflicting classifications of pathogenicity (Oct 24, 2023)
6-131576680-A-G		Arginase deficiency	Conflicting classifications of pathogenicity (Jan 21, 2024)
6-131576681-G-A		Arginase deficiency	Uncertain significance (Mar 25, 2021)
6-131576681-GA-G		Arginase deficiency	Pathogenic (Jul 01, 1990)
6-131576685-G-A		Arginase deficiency	Conflicting classifications of pathogenicity (Aug 07, 2020)
6-131576686-C-T		Arginase deficiency	Likely benign (Apr 12, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MED23	protein_coding	protein_coding	ENST00000368068	29	54264

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.10e-8	1.00	125665	0	83	125748	0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.73	369	728	0.507	0.0000371	9047
Missense in Polyphen		144	368.6	0.39067		4718
Synonymous	1.21	232	257	0.904	0.0000132	2589
Loss of Function	5.09	27	74.4	0.363	0.00000404	862

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000568	0.000568
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000436	0.000435
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000353	0.000352
Middle Eastern	0.000436	0.000435
South Asian	0.000461	0.000457
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for transcriptional activation subsequent to the assembly of the pre-initiation complex (By similarity). 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 pre-initiation complex with RNA polymerase II and the general transcription factors. Required for transcriptional activation by adenovirus E1A protein. Required for ELK1-dependent transcriptional activation in response to activated Ras signaling. {ECO:0000250, ECO:0000269|PubMed:10353252, ECO:0000269|PubMed:14759369, ECO:0000269|PubMed:16595664}.
• Disease: DISEASE: Mental retardation, autosomal recessive 18 (MRT18) [MIM:614249]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21868677}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: WNT-Ncore;Developmental Biology;Gene expression (Transcription);Generic Transcription Pathway;Hedgehog;RNA Polymerase II Transcription;Transcriptional regulation of white adipocyte differentiation (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.412
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.48

Haploinsufficiency Scores

• pHI: 0.123
• hipred: Y
• hipred_score: 0.694
• ghis: 0.691

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.932

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Med23
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: med23
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;positive regulation of nucleic acid-templated transcription
• Cellular component: nucleoplasm;transcription factor complex
• Molecular function: transcription coactivator activity;protein binding