MED25 (mediator complex subunit 25)

Gene

• Entrez ID: 81857
• Gene name: Mediator complex subunit 25
• Gene symbol: MED25
• Synonyms (NCBI Gene): ACID1, ARC92, BVSYS, CMT2B2, P78, PTOV2, TCBAP0758
• Chromosome: 19
• Chromosome location: 19q13.33
• Summary: This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in p

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs142353864	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs535472885	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs776291104	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1223073957	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555802864	C>T	Likely-pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT052170	hsa-let-7b-5p	CLASH	23622248
MIRT043009	hsa-miR-324-3p	CLASH	23622248
MIRT038966	hsa-miR-21-3p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	17641689
GO:0001223	Function	Transcription coactivator binding	IPI	17641689
GO:0005515	Function	Protein binding	IPI	17641689, 21378963, 21378965, 24882805, 25281560, 25792360, 32296183, 33961781, 35271311
GO:0005634	Component	Nucleus	IDA	24882805
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005667	Component	Transcription regulator complex	IBA
GO:0016592	Component	Mediator complex	IBA
GO:0032968	Process	Positive regulation of transcription elongation by RNA polymerase II	NAS	11559591
GO:0035563	Process	Positive regulation of chromatin binding	IMP	17641689
GO:0042974	Function	Nuclear retinoic acid receptor binding	IPI	17641689
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	17641689
GO:0046965	Function	Nuclear retinoid X receptor binding	IPI	17641689
GO:0048147	Process	Negative regulation of fibroblast proliferation	IMP	17641689
GO:0051123	Process	RNA polymerase II preinitiation complex assembly	NAS	11559591
GO:0060261	Process	Positive regulation of transcription initiation by RNA polymerase II	NAS	11559591
GO:0070847	Component	Core mediator complex	IPI	24882805
GO:2001178	Process	Positive regulation of mediator complex assembly	IMP	17641689

Other IDs

• MIM: 610197
• HGNC: 28845
• e!Ensembl: ENSG00000104973

Protein

• UniProt ID: Q71SY5
• Protein name: Mediator of RNA polymerase II transcription subunit 25 (Activator interaction domain-containing protein 1) (Activator-recruited cofactor 92 kDa component) (ARC92) (Mediator complex subunit 25) (p78)
• Protein 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 RN
• PDB: 2KY6, 2L23, 2L6U, 2XNF, 7EMF, 7LBM, 8GXQ, 8GXS, 8T9D
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF11265	Med25_VWA	12 → 226	Mediator complex subunit 25 von Willebrand factor type A	Family
  PF11235	Med25_SD1	228 → 383	Mediator complex subunit 25 synapsin 1	Domain
  PF11232	Med25	396 → 546	Mediator complex subunit 25 PTOV activation and synapsin 2	Domain
  PF11244	Med25_NR-box	658 → 747	Mediator complex subunit 25 C-terminal NR box-containing	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed. Highest levels in brain, heart, kidney, peripheral leukocytes, placenta, skeletal muscle and spleen. {ECO:0000269|PubMed:14657022, ECO:0000269|PubMed:14983011}.
• Sequence:

  MVPGSEGPARAGSVVADVVFVIEGTANLGPYFEGLRKHYLLPAIEYFNGGPPAETDFGGD
  YGGTQYSLVVFNTVDCAPESYVQCHAPTSSAYEFVTWLDGIKFMGGGGESCSLIAEGLST
  ALQLFDDFKKMREQIGQTHRVCLLICNSPPYLLPAVESTTYSGCTTENLVQQIGERGIHF
  SIVSPRKLPALRLLFEKAAPPALLEPLQPPTDVSQDPRHMVLVRGLVLPVGGGSAPGPLQ
  SKQPVPLPPAAPSGATLSAAPQQPLPPVPPQYQVPGNLSAAQVAAQNAVEAAKNQKAGLG
  PRFSPITPLQQAAPGVGPPFSQAPAPQLPPGPPGAPKPPPASQPSLVSTVAPGSGLAPTA
  QPGAPSMAGTVAPGGVSGPSPAQLGAPALGGQQSVSNKLLAWSGVLEWQEKPKPASVDAN
  TKLTRSLPCQVYVNHGENLKTEQWPQKLIMQLIPQQLLTTLGPLFRNSRMVQFHFTNKDL
  ESLKGLYRIMGNGFAGCVHFPHTAPCEVRVLMLLYSSKKKIFMGLIPYDQSGFVNGIRQV
  ITNHKQVQQQKLEQQQRGMGGQQAPPGLGPILEDQARPSQNLLQLRPPQPQPQGTVGASG
  ATGQPQPQGTAQPPPGAPQGPPGAASGPPPPGPILRPQNPGANPQLRSLLLNPPPPQTGV
  PPPQASLHHLQPPGAPALLPPPHQGLGQPQLGPPLLHPPPAQSWPAQLPPRAPLPGQMLL
  SGGPRGPVPQPGLQPSVMEDDILMDLI

• Sequence length: 747

Pathways

Reactome:

PPARA activates gene expression
Generic Transcription Pathway
Transcriptional regulation of white adipocyte differentiation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Charcot-Marie-Tooth disease type 2	Likely pathogenic; Pathogenic	rs781140315	RCV000689030	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome	Likely pathogenic; Pathogenic	rs781140315, rs794729668, rs2514495299	RCV004556753 RCV000185605 RCV003988254	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder	Likely pathogenic	rs551069830	RCV001374945	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth disease	Benign; Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar ClinVar, Disgenet ClinVar, Disgenet ClinVar, Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Charcot-Marie-Tooth disease type 2B2	Conflicting classifications of pathogenicity; Uncertain significance; Benign; Likely benign	ClinVar ClinGen, ClinVar, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2B2	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, TYPE 2B2	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY MOTOR AND SENSORY-NEUROPATHY TYPE II	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MED25-related disorder	Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental delay	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polyneuropathy	Benign; Likely benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tip-toe gait	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absence of septum pellucidum	Absence Of Septum Pellucidum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	BEFREE	26556829		★☆☆☆☆ Found in Text Mining only
Alopecia	Alopecia	BEFREE	10942113		★☆☆☆☆ Found in Text Mining only
Alopecia Areata	Alopecia Areata	BEFREE	10942113		★☆☆☆☆ Found in Text Mining only
Anemia, Hemolytic	Anemia	BEFREE	28214868		★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	30039206	Associate	★☆☆☆☆ Found in Text Mining only
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal recessive non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME	Basel-Vanagaite-Smirin-Yosef Syndrome	GENOMICS_ENGLAND_DG	25527630, 25792360, 30800049		★☆☆☆☆ Found in Text Mining only
BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME	Basel-Vanagaite-Smirin-Yosef Syndrome	ORPHANET_DG	25792360		★☆☆☆☆ Found in Text Mining only
BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME	Basel-Vanagaite-Smirin-Yosef Syndrome	UNIPROT_DG	25792360		★☆☆☆☆ Found in Text Mining only
Basel-Vanagaite-Smirin-Yosef syndrome	Basel-Vanagaite-Smirin-Yosef Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME	Basel-Vanagaite-Smirin-Yosef Syndrome	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME	Basel-Vanagaite-Smirin-Yosef Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Blepharophimosis	Blepharophimosis	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	29144746		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	34137598	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	35069777	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Central Core Myopathy (disorder)	Myopathy	BEFREE	31299492		★☆☆☆☆ Found in Text Mining only
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	BEFREE	17347251, 19290556, 30039206		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Charcot-Marie-Tooth disease type 2B2	Charcot-Marie-Tooth Disease	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Charcot-Marie-Tooth disease, Type 2B1	Charcot-Marie-Tooth disease	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth disease, Type 2B2	Charcot-Marie-Tooth disease	GENOMICS_ENGLAND_DG	19290556		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth disease, Type 2B2	Charcot-Marie-Tooth disease	UNIPROT_DG	19290556		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth disease, Type 2B2	Charcot-Marie-Tooth disease	BEFREE	30039206		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth disease, Type 2B2	Charcot-Marie-Tooth disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth disease, Type 2B2	Charcot-Marie-Tooth disease	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	21919647		★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	31255603		★☆☆☆☆ Found in Text Mining only
Congenital Hyperinsulinism	Hyperinsulinemic hypoglycemia	BEFREE	29116340		★☆☆☆☆ Found in Text Mining only
Cortical Dysplasia	Cortical Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	30599971		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	30599971		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	22952853		★☆☆☆☆ Found in Text Mining only
Distal amyotrophy	Distal amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	10942113		★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	28575990		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	28575990		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	28575990		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	25527630, 25792360		★☆☆☆☆ Found in Text Mining only
Kidney Calculi	Kidney stone	BEFREE	28616648		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	29144746		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	21919647		★☆☆☆☆ Found in Text Mining only
Maturity onset diabetes mellitus in young	Mason type diabetes	BEFREE	22952853		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	25792360		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcornea	Microcornea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28575990		★☆☆☆☆ Found in Text Mining only
Nephrolithiasis	Nephrolithiasis	BEFREE	28616648		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	28927789, 29644528		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	19290556		★☆☆☆☆ Found in Text Mining only
Nevus	Nevus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral axonal neuropathy	Peripheral axonal neuropathy	BEFREE	26556829		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	26556829	Associate	★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Posteriorly rotated ear	Posteriorly Rotated Ear	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	21110951		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Salaam Seizures	Salaam Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	BEFREE	25792360		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia Hereditary	Hereditary spastic paraplegia	Pubtator	26556829	Associate	★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	34137598, 38527936	Associate	★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	30362597		★☆☆☆☆ Found in Text Mining only