MED12L

mediator complex subunit 12L, the group of Mediator complex

Basic information

Region (hg38): 3:151085286-151437072

Links

ENSG00000144893 ∙ NCBI:116931 ∙ OMIM:611318 ∙ HGNC:16050 ∙ Uniprot:Q86YW9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Nizon-Isidor syndrome (Moderate), mode of inheritance: AD
• Nizon-Isidor syndrome (Moderate), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• Nizon-Isidor syndrome (Moderate), mode of inheritance: AD
• Nizon-Isidor syndrome (Strong), mode of inheritance: AD
• Nizon-Isidor syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nizon-Isidor syndrome	AD	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	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	31155615

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MED12L gene.

• not_provided (231 variants)
• not_specified (219 variants)
• Inborn_genetic_diseases (204 variants)
• Nizon-Isidor_syndrome (68 variants)
• MED12L-related_disorder (36 variants)
• Platelet-type_bleeding_disorder_8 (9 variants)
• P2RY12-related_disorder (6 variants)
• Intellectual_disability (4 variants)
• Impaired_ADP-induced_platelet_aggregation (3 variants)
• Developmental_disorder (3 variants)
• Thrombocytopenia (2 variants)
• Neurodevelopmental_disorder (2 variants)
• Abnormal_bleeding (2 variants)
• See_cases (2 variants)
• MED12L-related_neurodevelopmental_disorder (2 variants)
• Abnormal_platelet_function (1 variants)
• MED12L-associated_neurodevelopmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED12L gene is commonly pathogenic or not. These statistics are base on transcript: NM_001393769.1. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	21	1	24
missense	1	1	337	35	1	375
nonsense	2	11	1			14
start loss						0
frameshift	3	4	1			8
splice donor/acceptor (+/-2bp)	2	6	2			10
Total	8	22	343	56	2

Highest pathogenic variant AF is 0.000047091

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MED12L	protein_coding	protein_coding	ENST00000474524	43	351377

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.51e-10	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.13	869	1.17e+3	0.742	0.0000645	14032
Missense in Polyphen		251	449.12	0.55888		5520
Synonymous	-0.464	465	452	1.03	0.0000268	4124
Loss of Function	9.13	15	125	0.120	0.00000683	1383

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000154	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.0000990	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be a 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 (By similarity). {ECO:0000250}.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.345
• rvis_EVS: -2.54
• rvis_percentile_EVS: 0.88

Haploinsufficiency Scores

• pHI: 0.385
• hipred: Y
• hipred_score: 0.627
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.763

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Med12l

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;positive regulation of nucleic acid-templated transcription
• Cellular component: nucleus;mediator complex
• Molecular function: transcription coactivator activity;beta-catenin binding