MED25

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

Basic information

Region (hg38): 19:49818282-49840383

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 (698 variants)
Inborn_genetic_diseases (91 variants)
not_provided (77 variants)
Charcot-Marie-Tooth_disease (68 variants)
Congenital_cataract-microcephaly-nevus_flammeus_simplex-severe_intellectual_disability_syndrome (48 variants)
not_specified (18 variants)
MED25-related_disorder (15 variants)
Charcot-Marie-Tooth_disease_type_2B2 (11 variants)
Tip-toe_gait (5 variants)
Polyneuropathy (3 variants)
Neurodevelopmental_disorder (2 variants)
Neurodevelopmental_delay (2 variants)
Autism (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. These statistics are base on transcript: NM_000030973.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	228 clinvar	5 clinvar	242
missense	1 clinvar	4 clinvar	276 clinvar	11 clinvar		292
nonsense		2 clinvar	5 clinvar			7
start loss		1				1
frameshift	1 clinvar	7 clinvar	20 clinvar			28
splice donor/acceptor (+/-2bp)		1 clinvar	5 clinvar			6
Total	2	15	315	239	5

Highest pathogenic variant AF is 0.000027294134

Loading clinvar variants...

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