MED25

mediator complex subunit 25, the group of Mediator complex|MicroRNA protein coding host genes

Basic information

Region (hg38): 19:49818281-49840383

Links

ENSG00000104973 ∙ NCBI:81857 ∙ OMIM:610197 ∙ HGNC:28845 ∙ Uniprot:Q71SY5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (Definitive), mode of inheritance: AR
• congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (Moderate), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 2B2 (Supportive), mode of inheritance: AR
• congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (Supportive), mode of inheritance: AR
• congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 2B2 (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Basel-Vanagait-Smirin-Yosef syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic; Ophthalmologic	19290556; 25792360

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MED25 gene.

• Charcot-Marie-Tooth disease type 2 (615 variants)
• Charcot-Marie-Tooth disease (71 variants)
• not provided (67 variants)
• Inborn genetic diseases (32 variants)
• Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (28 variants)
• not specified (21 variants)
• Charcot-Marie-Tooth disease type 2B2 (7 variants)
• Tip-toe gait (4 variants)
• Polyneuropathy (3 variants)
• Charcot-Marie-Tooth disease type 2B2;Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (3 variants)
• Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome;Charcot-Marie-Tooth disease type 2B2 (2 variants)
• Neurodevelopmental disorder (2 variants)
• Neurodevelopmental delay (2 variants)
• 8 conditions (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED25 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			7	175	5	187
missense	1		246	8	1	256
nonsense		1	5			6
start loss						0
frameshift	1	1	20			22
inframe indel			11			11
splice donor/acceptor (+/-2bp)		2	3			5
splice region			19	39	4	62
non coding			2	87	16	105
Total	2	4	294	270	22

Highest pathogenic variant AF is 0.0000526

Variants in MED25

This is a list of pathogenic ClinVar variants found in the MED25 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-49818330-A-G		not specified • Charcot-Marie-Tooth disease • Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome	Benign (Oct 20, 2023)
19-49818343-T-G		Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome	Likely pathogenic (Jan 24, 2024)
19-49818345-G-C		Charcot-Marie-Tooth disease type 2 • Charcot-Marie-Tooth disease	Uncertain significance (Jun 25, 2022)
19-49818348-CCCGGGTCCGAGGGCCCGGCCCGCG-C		Charcot-Marie-Tooth disease type 2	Uncertain significance (Nov 07, 2022)
19-49818350-C-T		Charcot-Marie-Tooth disease type 2	Likely benign (Oct 07, 2022)
19-49818356-C-T		Charcot-Marie-Tooth disease type 2	Likely benign (Jul 31, 2019)
19-49818357-G-C		Charcot-Marie-Tooth disease type 2	Uncertain significance (Aug 16, 2022)
19-49818361-G-T		Charcot-Marie-Tooth disease type 2	Uncertain significance (Feb 14, 2021)
19-49818364-C-A			Uncertain significance (Sep 29, 2017)
19-49818364-C-T		Charcot-Marie-Tooth disease type 2	Uncertain significance (Aug 24, 2021)
19-49818369-C-T		Charcot-Marie-Tooth disease type 2	Uncertain significance (Mar 06, 2022)
19-49818370-G-T		Charcot-Marie-Tooth disease type 2	Uncertain significance (Dec 12, 2021)
19-49818377-G-C		Charcot-Marie-Tooth disease type 2	Likely benign (Mar 04, 2022)
19-49818389-C-T		Charcot-Marie-Tooth disease type 2	Likely benign (May 25, 2023)
19-49818399-T-A		Charcot-Marie-Tooth disease type 2	Uncertain significance (Mar 13, 2022)
19-49818402-G-A		Charcot-Marie-Tooth disease type 2	Uncertain significance (Aug 30, 2021)
19-49818422-C-T		Charcot-Marie-Tooth disease type 2	Likely benign (Jul 31, 2020)
19-49818428-A-G		Charcot-Marie-Tooth disease type 2	Likely benign (Feb 23, 2022)
19-49818434-C-T		Charcot-Marie-Tooth disease type 2 • Charcot-Marie-Tooth disease • Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome	Benign/Likely benign (Jan 19, 2024)
19-49818437-C-T		Charcot-Marie-Tooth disease type 2	Benign (Mar 04, 2022)
19-49818439-A-G		Charcot-Marie-Tooth disease type 2	Uncertain significance (Oct 08, 2022)
19-49818439-AG-A		Charcot-Marie-Tooth disease type 2	Uncertain significance (Apr 26, 2019)
19-49818443-G-A		Charcot-Marie-Tooth disease type 2	Likely benign (Apr 16, 2023)
19-49818443-G-T		Charcot-Marie-Tooth disease type 2	Likely benign (Oct 10, 2022)
19-49818448-G-A		Charcot-Marie-Tooth disease type 2 • Charcot-Marie-Tooth disease	Uncertain significance (Oct 31, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MED25	protein_coding	protein_coding	ENST00000312865	18	20535

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.42e-7	1.00	125666	0	82	125748	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	380	455	0.835	0.0000288	4691
Missense in Polyphen		124	171.02	0.72505		1798
Synonymous	-2.45	247	203	1.22	0.0000145	1631
Loss of Function	3.28	17	39.1	0.435	0.00000201	403

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000646	0.000565
Ashkenazi Jewish	0.000211	0.000198
East Asian	0.000877	0.000870
Finnish	0.0000484	0.0000462
European (Non-Finnish)	0.000333	0.000308
Middle Eastern	0.000877	0.000870
South Asian	0.000429	0.000425
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. Required for RARA/RXRA-mediated transcription. {ECO:0000269|PubMed:14657022, ECO:0000269|PubMed:14983011, ECO:0000269|PubMed:17641689}.
• Disease: DISEASE: Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) [MIM:616449]: An autosomal recessive syndrome characterized by eye, brain, cardiac and palatal abnormalities as well as growth retardation, microcephaly and severe intellectual disability. {ECO:0000269|PubMed:25792360}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Developmental Biology;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Transcriptional regulation of white adipocyte differentiation (Consensus)

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.433
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.78

Haploinsufficiency Scores

• pHI: 0.160
• hipred: Y
• hipred_score: 0.547
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.517

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Med25
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); limbs/digits/tail phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: med25
• Affected structure: peripheral neuron
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;positive regulation of chromatin binding;positive regulation of transcription by RNA polymerase II;negative regulation of fibroblast proliferation;positive regulation of cell cycle arrest;positive regulation of mediator complex assembly
• Cellular component: nucleoplasm;mediator complex;nuclear transcription factor complex
• Molecular function: protein binding;transcription factor binding;retinoic acid receptor binding;retinoid X receptor binding