MID2

Chr XXLR

midline 2

Also known as: FXY2, MRX101, RNF60, TRIM1, XLID101

NCBI Gene: 11043 ENSG00000080561 UniProt: Q9UJV3 OMIM: 300204

MID2 encodes an E3 ubiquitin ligase that mediates microtubule stabilization and regulates LRRK2 protein degradation in neurons through polyubiquitination. Mutations cause X-linked intellectual developmental disorder with males being affected and females typically being carriers. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.496), suggesting some tolerance to protein-disrupting changes.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Intellectual developmental disorder, X-linked 101MIM #300928

XLR

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.175

Z-score 3.39

OE 0.25 (0.14–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.58Z-score

OE missense 0.74 (0.66–0.83)

217 obs / 293.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.14–0.50)

0≤0.351.4

Missense OE?0.74 (0.66–0.83)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 6 / 23.9Missense obs/exp: 217 / 293.3Syn Z: 1.12

Background carrier burden — how many people carry a rare variant somewhere in MID2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

469 rare PASS variants

Rare truncating (LoF)

1 in 11,000

31 rare PASS variants

Rare synonymous (reference)

1 in 240

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MID2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 290	1 in 15,000
South Asian	~36k	1 in 150	none seen
Remaining (unassigned)	~31k	1 in 190	≈ 1 in 7,600
European (Finnish)	~27k	1 in 1,200	1 in 4,500
Admixed American	~23k	1 in 220	≈ 1 in 5,900
African / African American	~21k	1 in 110	1 in 1,300
East Asian	~20k	1 in 190	≈ 1 in 10,000
Ashkenazi Jewish	~13k	≈ 1 in 6,400	≈ 1 in 13,000
Middle Eastern	~2,758	1 in 210	≈ 1 in 2,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓