MID1

midline 1, the group of Tripartite motif family|Ring finger proteins|Fibronectin type III domain containing

Basic information

Region (hg38): X:10445309-10833654

Links

ENSG00000101871 ∙ ∙ OMIM:300552 ∙ HGNC:7095 ∙ Uniprot:O15344 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked Opitz G/BBB syndrome (Definitive), mode of inheritance: XLR
• X-linked Opitz G/BBB syndrome (Strong), mode of inheritance: XL
• X-linked Opitz G/BBB syndrome (Definitive), mode of inheritance: XL
• X-linked Opitz G/BBB syndrome (Definitive), mode of inheritance: XL
• X-linked Opitz G/BBB syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Opitz GBBB syndrome, type I	XL	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Neurologic	9354791; 11030761; 12833403; 15121778; 15558842; 16619207; 20301502; 20671548; 22407675

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MID1 gene.

• not provided (163 variants)
• Inborn genetic diseases (40 variants)
• X-linked Opitz G/BBB syndrome (38 variants)
• not specified (32 variants)
• MID1-related condition (3 variants)
• Dandy-Walker syndrome (1 variants)
• Low-set ears;Hypertelorism;Abnormal facial shape;Corpus callosum, agenesis of;Clinodactyly of the 5th finger (1 variants)
• History of neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MID1 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	40	15	59
missense	1	3	68	8	2	82
nonsense	9	5				14
start loss						0
frameshift	11	5	1			17
inframe indel			4			4
splice donor/acceptor (+/-2bp)	2	2				4
splice region	1			3	5	9
non coding			1	7	12	20
Total	23	15	78	55	29

Variants in MID1

This is a list of pathogenic ClinVar variants found in the MID1 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-10449371-C-T			Likely benign (Dec 05, 2023)
X-10449372-G-A		not specified • X-linked Opitz G/BBB syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 01, 2024)
X-10449383-T-C			Likely benign (Nov 15, 2023)
X-10449384-G-A		Inborn genetic diseases • MID1-related disorder	Conflicting classifications of pathogenicity (Jan 25, 2024)
X-10449386-G-A			Likely benign (Aug 05, 2023)
X-10449389-G-A			Likely benign (Jan 14, 2024)
X-10449389-G-C			Benign (Jan 24, 2024)
X-10449394-A-G			Likely benign (Jan 21, 2024)
X-10449404-G-A		Inborn genetic diseases	Benign (Jan 30, 2024)
X-10449419-G-A		MID1-related disorder	Likely benign (Nov 10, 2023)
X-10449424-T-G			Uncertain significance (Dec 03, 2021)
X-10449428-C-CA			Likely pathogenic (Jun 05, 2023)
X-10449429-A-G			Likely pathogenic (Oct 25, 2023)
X-10449435-T-C			Uncertain significance (May 19, 2022)
X-10449436-TGTTCCACACGGTGAAGGTGGGGC-GCCCCACCTTCACCGTGTGGAACA		X-linked Opitz G/BBB syndrome	Uncertain significance (Sep 02, 2022)
X-10449446-G-A			Likely benign (Dec 03, 2022)
X-10449448-T-G		X-linked Opitz G/BBB syndrome	Likely pathogenic (Aug 10, 2021)
X-10449454-TG-T		X-linked Opitz G/BBB syndrome	Pathogenic (Sep 13, 2018)
X-10449470-C-T			Likely benign (Sep 20, 2023)
X-10449476-T-G			Benign (Jan 11, 2024)
X-10449479-G-A			Likely benign (Jul 23, 2022)
X-10449482-G-C			Uncertain significance (Apr 09, 2023)
X-10449484-C-T		not specified	Uncertain significance (Jun 19, 2018)
X-10449485-G-A			Likely benign (Jan 21, 2024)
X-10449488-G-A			Likely benign (Jan 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MID1	protein_coding	protein_coding	ENST00000317552	9	438424

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.980	0.0203	125716	0	3	125719	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.92	152	293	0.519	0.0000252	4402
Missense in Polyphen		37	116.77	0.31686		1732
Synonymous	-0.187	122	119	1.02	0.0000107	1298
Loss of Function	3.81	2	20.7	0.0965	0.00000160	336

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000122	0.00000879
Middle Eastern	0.000217	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination. {ECO:0000269|PubMed:10400985, ECO:0000269|PubMed:11685209, ECO:0000269|PubMed:22613722}.
• Disease: DISEASE: Opitz GBBB syndrome 1 (GBBB1) [MIM:300000]: A congenital midline malformation syndrome characterized by hypertelorism, genital-urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects. {ECO:0000269|PubMed:11030761, ECO:0000269|PubMed:15558842, ECO:0000269|PubMed:9354791, ECO:0000269|PubMed:9718340}. Note=The disease is caused by mutations affecting the gene represented in this entry. MID1 mutations produce proteins with a decreased affinity for microtubules.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Cytokine Signaling in Immune system;Immune System;Interferon gamma signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.290

Intolerance Scores

• loftool: 0.448
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.77

Haploinsufficiency Scores

• pHI: 0.177
• hipred: Y
• hipred_score: 0.746
• ghis: 0.615

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mid1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo 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); normal 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); growth/size/body region phenotype

Gene ontology

• Biological process: microtubule cytoskeleton organization;negative regulation of microtubule depolymerization;pattern specification process;positive regulation of stress-activated MAPK cascade;protein localization to microtubule;interferon-gamma-mediated signaling pathway
• Cellular component: spindle;cytosol;microtubule;microtubule associated complex;cytoplasmic microtubule
• Molecular function: protein binding;microtubule binding;zinc ion binding;transferase activity;ubiquitin protein ligase binding;identical protein binding;protein homodimerization activity;protein heterodimerization activity;phosphoprotein binding