MED12
mediator complex subunit 12, the group of Mediator complex
Basic information
Region (hg38): X:71118543-71144103
Previous symbols: [ "TNRC11", "FGS1" ]
Links
Phenotypes
GenCC
Source:
- X-linked intellectual disability with marfanoid habitus (Supportive), mode of inheritance: XL
- FG syndrome 1 (Supportive), mode of inheritance: XL
- blepharophimosis - intellectual disability syndrome, MKB type (Supportive), mode of inheritance: XL
- FG syndrome 1 (Definitive), mode of inheritance: XL
- X-linked intellectual disability with marfanoid habitus (Definitive), mode of inheritance: XL
- blepharophimosis - intellectual disability syndrome, MKB type (Strong), mode of inheritance: XL
- cholestasis-pigmentary retinopathy-cleft palate syndrome (Strong), mode of inheritance: XL
- X-linked intellectual disability with marfanoid habitus (Strong), mode of inheritance: XL
- FG syndrome 1 (Strong), mode of inheritance: XL
- MED12-related intellectual disability syndrome (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hardikar syndrome | XL | Cardiovascular | Among other findings in Hardikar syndrome, congenital cardiovascular anomalies may occur, and early identificaiton and management may be beneficial | Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic | 4365204; 6711603; 3322000; 10405444; 10508979; 17036352; 17334363; 17369503; 18973276; 19938245; 20301719; 20507344; 20981778; 23395478; 33244166 |
| Aortic root dilatation and ventricular septal defect were reported in one individual and his maternal uncle |
ClinVar
This is a list of variants' phenotypes submitted to
- FG_syndrome (1381 variants)
- Familial_thoracic_aortic_aneurysm_and_aortic_dissection (592 variants)
- not_provided (578 variants)
- not_specified (137 variants)
- FG_syndrome_1 (103 variants)
- MED12-related_disorder (92 variants)
- Blepharophimosis_-_intellectual_disability_syndrome,_MKB_type (61 variants)
- X-linked_intellectual_disability_with_marfanoid_habitus (57 variants)
- Cholestasis-pigmentary_retinopathy-cleft_palate_syndrome (35 variants)
- Uterine_leiomyoma (28 variants)
- MED12-related_intellectual_disability_syndrome (15 variants)
- Intellectual_disability (12 variants)
- Inborn_genetic_diseases (10 variants)
- See_cases (5 variants)
- Cardiovascular_phenotype (3 variants)
- Nonspecific_Intellectual_Disability (3 variants)
- Neurodevelopmental_disorder (2 variants)
- History_of_neurodevelopmental_disorder (2 variants)
- Global_developmental_delay (2 variants)
- X-linked_MED12-related_disorder (2 variants)
- Abnormal_facial_shape (2 variants)
- Glioblastoma (1 variants)
- Corpus_callosum,_agenesis_of (1 variants)
- Syndromic_intellectual_disability (1 variants)
- Expressive_language_delay (1 variants)
- MED12-related_neurodevelopmental_delay (1 variants)
- Microcephaly (1 variants)
- Angiosarcoma (1 variants)
- Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
- Imperforate_anus (1 variants)
- Dilated_cardiomyopathy_1Y (1 variants)
- Seizure (1 variants)
- Simpson-Golabi-Behmel_syndrome_type_1 (1 variants)
- Wilms_tumor_1 (1 variants)
- Ventriculomegaly (1 variants)
- Neurodevelopmental_delay (1 variants)
- Ehlers-Danlos_syndrome,_classic_type (1 variants)
- Absent_speech (1 variants)
- Nephroblastoma (1 variants)
- Broad_thumb (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005120.3. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 21 | 539 | 25 | 585 | ||
| missense | 48 | 710 | 136 | 17 | 917 | |
| nonsense | 12 | 24 | ||||
| start loss | 0 | |||||
| frameshift | 18 | |||||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| Total | 26 | 71 | 743 | 675 | 42 |
Highest pathogenic variant AF is 0.000005477511
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MED12 | protein_coding | protein_coding | ENST00000374080 | 45 | 23898 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 1.91e-13 | 121517 | 1 | 0 | 121518 | 0.00000411 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 6.58 | 343 | 898 | 0.382 | 0.0000742 | 14199 |
| Missense in Polyphen | 66 | 275 | 0.24 | 4257 | ||
| Synonymous | 1.25 | 314 | 343 | 0.914 | 0.0000269 | 4324 |
| Loss of Function | 8.53 | 2 | 88.7 | 0.0226 | 0.00000676 | 1318 |
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 | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000127 | 0.00000916 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway. {ECO:0000269|PubMed:16565090, ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:17000779}.;
- Disease
- DISEASE: Lujan-Fryns syndrome (LUJFRYS) [MIM:309520]: Clinically, Lujan-Fryns syndrome can be distinguished from Opitz-Kaveggia syndrome by tall stature, hypernasal voice, hyperextensible digits and high nasal root. {ECO:0000269|PubMed:17369503}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ohdo syndrome, X-linked (OHDOX) [MIM:300895]: A syndrome characterized by mental retardation, feeding problems, and distinctive facial appearance with coarse facial features, severe blepharophimosis, ptosis, a bulbous nose, micrognathia and a small mouth. Dental hypoplasia and deafness can be considered as common manifestations of the syndrome. Male patients show cryptorchidism and scrotal hypoplasia. {ECO:0000269|PubMed:23395478}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Thyroid hormone signaling pathway - Homo sapiens (human);WNT-Ncore;Developmental Biology;Gene expression (Transcription);Generic Transcription Pathway;Hedgehog;RNA Polymerase II Transcription;Transcriptional regulation of white adipocyte differentiation;Regulation of nuclear beta catenin signaling and target gene transcription
(Consensus)
Recessive Scores
- pRec
- 0.306
Intolerance Scores
- loftool
- rvis_EVS
- -1
- rvis_percentile_EVS
- 8.47
Haploinsufficiency Scores
- pHI
- 0.462
- hipred
- Y
- hipred_score
- 0.673
- ghis
- 0.581
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.952
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Med12
- Phenotype
- growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; skeleton phenotype; embryo phenotype; 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); 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); limbs/digits/tail 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);
Zebrafish Information Network
- Gene name
- med12
- Affected structure
- neutrophil
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- neural tube closure;regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;endoderm development;heart development;oligodendrocyte development;Schwann cell development;protein ubiquitination;stem cell population maintenance;spinal cord development;negative regulation of Wnt signaling pathway;intracellular steroid hormone receptor signaling pathway;androgen receptor signaling pathway;post-anal tail morphogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic neurocranium morphogenesis;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;axis elongation involved in somitogenesis;embryonic brain development
- Cellular component
- ubiquitin ligase complex;nucleus;nucleoplasm;membrane;mediator complex
- Molecular function
- RNA polymerase II distal enhancer sequence-specific DNA binding;chromatin binding;transcription coregulator activity;transcription coactivator activity;protein binding;beta-catenin binding;protein C-terminus binding;protein domain specific binding;nuclear receptor transcription coactivator activity;signaling receptor activity;vitamin D receptor binding;thyroid hormone receptor binding;ubiquitin protein ligase activity