MID2

midline 2, the group of Fibronectin type III domain containing|Tripartite motif family|Ring finger proteins

Basic information

Region (hg38): X:107825754-107931637

Links

ENSG00000080561 ∙ NCBI:11043 ∙ OMIM:300204 ∙ HGNC:7096 ∙ Uniprot:Q9UJV3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• intellectual disability, X-linked 101 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 101	XL	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; Neurologic	24115387

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MID2 gene.

• not provided (18 variants)
• Intellectual disability, X-linked 101 (12 variants)
• Inborn genetic diseases (11 variants)
• not specified (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MID2 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				4	4	8
missense		1	27		1	29
nonsense		1				1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1	1	2
non coding				2		2
Total	1	2	28	6	5

Highest pathogenic variant AF is 0.0000178

Variants in MID2

This is a list of pathogenic ClinVar variants found in the MID2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-107840832-G-A		not specified	Uncertain significance (Dec 21, 2022)
X-107840840-G-A		not specified	Uncertain significance (Feb 13, 2024)
X-107840845-A-C		Intellectual disability, X-linked 101	Benign (Sep 05, 2021)
X-107840973-T-G		Intellectual disability, X-linked 101	Uncertain significance (Dec 23, 2020)
X-107840979-G-C		not specified	Uncertain significance (Mar 07, 2024)
X-107841026-C-T		not specified	Uncertain significance (Jan 17, 2024)
X-107841027-G-A			Uncertain significance (Jul 01, 2022)
X-107841027-G-T		not specified	Uncertain significance (Aug 12, 2021)
X-107841038-A-G		Intellectual disability, X-linked 101	Uncertain significance (May 31, 2020)
X-107841062-T-A		not specified	Uncertain significance (May 19, 2022)
X-107841067-C-G		not specified	Uncertain significance (Apr 18, 2022)
X-107841113-G-T		Intellectual disability, X-linked 101	Uncertain significance (Mar 20, 2024)
X-107841155-C-G		not specified	Uncertain significance (Apr 18, 2023)
X-107841155-C-T		not specified	Uncertain significance (Dec 11, 2023)
X-107841156-G-A		Intellectual disability, X-linked 101	Uncertain significance (Mar 05, 2018)
X-107841225-A-G		not specified	Uncertain significance (Dec 15, 2022)
X-107841247-C-A			Benign (Dec 31, 2019)
X-107841332-C-T			Uncertain significance (Dec 01, 2016)
X-107841402-G-A			Likely benign (Jun 15, 2017)
X-107854646-G-A		not specified	Uncertain significance (Nov 11, 2015)
X-107903948-T-G			Likely benign (May 23, 2018)
X-107903989-T-C		not specified	Uncertain significance (Apr 10, 2023)
X-107904009-G-A		not specified	Uncertain significance (Aug 13, 2021)
X-107904041-C-T			Likely benign (Jan 03, 2019)
X-107904072-C-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MID2	protein_coding	protein_coding	ENST00000262843	10	101439

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.175	0.824	125717	3	7	125727	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.58	217	293	0.740	0.0000228	4881
Missense in Polyphen		87	132.55	0.65636		2220
Synonymous	1.12	93	108	0.863	0.00000810	1399
Loss of Function	3.39	6	23.9	0.251	0.00000200	372

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000225	0.000196
Ashkenazi Jewish	0.00	0.00
East Asian	0.000144	0.000109
Finnish	0.0000627	0.0000462
European (Non-Finnish)	0.0000367	0.0000264
Middle Eastern	0.000144	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in microtubule stabilization. {ECO:0000303|PubMed:24115387}.
• Disease: DISEASE: Mental retardation, X-linked 101 (MRX101) [MIM:300928]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non- syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. MRX101 clinical features include global developmental delay, hyperactivity often with aggressive outbursts, and seizures in some patients. Several affected individuals have long face, prominent ears, and squint or strabismus. {ECO:0000269|PubMed:24115387}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.141

Intolerance Scores

• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.585
• hipred: Y
• hipred_score: 0.743
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mid2

Gene ontology

• Biological process: positive regulation of autophagy;protein ubiquitination;negative regulation of viral transcription;protein localization to microtubule;positive regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;negative regulation of viral entry into host cell;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;negative regulation of viral release from host cell
• Cellular component: cytoplasm;microtubule;extracellular exosome
• Molecular function: microtubule binding;zinc ion binding;transferase activity;protein homodimerization activity;protein heterodimerization activity;phosphoprotein binding