MED12L

mediator complex subunit 12L, the group of Mediator complex

Basic information

Region (hg38): 3:151085285-151437072

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

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.

• Inborn genetic diseases (131 variants)
• not provided (123 variants)
• Nizon-Isidor syndrome (41 variants)
• not specified (12 variants)
• MED12L-related condition (12 variants)
• Platelet-type bleeding disorder 8 (7 variants)
• Impaired ADP-induced platelet aggregation (3 variants)
• Developmental disorder (2 variants)
• Neurodevelopmental disorder (2 variants)
• See cases (2 variants)
• MED12L-related neurodevelopmental disorder (2 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• Premature ovarian failure (1 variants)
• Abnormal platelet function (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.

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				3	2	5
missense			143	12	2	157
nonsense	2	7	2			11
start loss						0
frameshift		2				2
inframe indel			3			3
splice donor/acceptor (+/-2bp)		2	1			3
splice region			4	1	2	7
non coding		4	88	20	19	131
Total	2	15	237	35	23

Variants in MED12L

This is a list of pathogenic ClinVar variants found in the MED12L region.

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

Position	Type	Phenotype	Significance	ClinVar
3-151086958-A-G		Inborn genetic diseases	Uncertain significance (Nov 07, 2023)
3-151086987-C-T		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
3-151087000-A-G			Uncertain significance (Feb 28, 2023)
3-151087008-G-T			Uncertain significance (Oct 25, 2022)
3-151087012-C-G		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
3-151087022-G-C			Uncertain significance (Jul 15, 2022)
3-151116351-C-T			Uncertain significance (Jan 12, 2023)
3-151116386-G-A		Nizon-Isidor syndrome	Uncertain significance (Dec 22, 2022)
3-151116405-A-G		Inborn genetic diseases	Uncertain significance (Mar 16, 2022)
3-151116422-A-G			Uncertain significance (Jun 28, 2023)
3-151116423-T-G			Uncertain significance (Jun 26, 2022)
3-151116442-G-A			Uncertain significance (Nov 29, 2022)
3-151122797-T-G		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
3-151122844-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
3-151122926-G-A		Nizon-Isidor syndrome	Likely pathogenic (-)
3-151122926-G-T			Uncertain significance (May 26, 2017)
3-151127887-G-T		Inborn genetic diseases	Uncertain significance (May 26, 2021)
3-151127892-G-A		Nizon-Isidor syndrome	Uncertain significance (May 04, 2022)
3-151127936-A-T		Inborn genetic diseases	Uncertain significance (Apr 28, 2021)
3-151127976-C-T		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
3-151156169-C-T		Nizon-Isidor syndrome	Likely pathogenic (Jan 26, 2024)
3-151156270-G-T		Inborn genetic diseases	Likely benign (Jan 21, 2022)
3-151156271-G-T			Uncertain significance (Jul 31, 2021)
3-151156284-T-G		not specified	Uncertain significance (Aug 29, 2022)
3-151156305-A-G		Nizon-Isidor syndrome • MED12L-related disorder	Uncertain significance (Mar 27, 2023)

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