MID2

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]

MANE transcript

NM_012216.4

Inheritance

ClinVar variants

P:5U:192B:20

Top phenotype

Intellectual developmental disorder, X-linked 101

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chrX:107,825,755-107,931,637

External References & Databases

Ensembl (ENSG00000080561)

Transcript & Mutation Effects

hg38 • Region Span ~105.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

non-syndromic X-linked intellectual disabilitySUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0019181

Submitter: Orphanet

intellectual disability, X-linked 101LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0010489

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked 101XL

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 24115387

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MID2 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 29

Intellectual disability, X-linked 101Total: 15

MID2-related disorderTotal: 5

Pyloric stenosisTotal: 1

AutismTotal: 1

Developmental delayTotal: 1

Esophageal atresiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012216.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			13 clinvar	13 clinvar	2 clinvar	28
missense		2 clinvar	160 clinvar	4 clinvar	1 clinvar	167
nonsense		1 clinvar	7 clinvar			8
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	1	4	192	17	3	217

Highest pathogenic variant AF is 0.000016574197

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012216.4	RefSeq	NP_036348.2	10	MANE Select
ENST00000262843.11	Ensembl	ENSP00000262843.6	10	MANE Select
NM_001382751.1	RefSeq	NP_001369680.1	9	Standard
NM_001382752.1	RefSeq	NP_001369681.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

microtubule binding
zinc ion binding
transferase activity
protein homodimerization activity
protein heterodimerization activity

Cellular Component

cytoplasm
microtubule
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262843
Coding exons: 10
Length: 101439
Individuals with no LoFs: 125717
Homozygous LoFs: 3
Heterozygous LoFs: 7
Defined: 125727
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.58	217	293	0.740	0.0000228	4881
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00015	0.00012	rare
Latino/Admixed American	0.000073	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00014	0.00011	rare
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000037	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

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