MBNL2

Chr 13

muscleblind like splicing regulator 2

Also known as: MBLL, MBLL39, PRO2032

NCBI Gene: 10150 ENSG00000139793 UniProt: Q5VZF2 OMIM: 607327

The protein regulates pre-mRNA alternative splicing by acting as either an activator or repressor for specific targets, and binds to CUG triplet repeat expansions in myotonic dystrophy cells. Mutations in this gene cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, affecting neurological development and seizure control. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.56), suggesting some tolerance to complete protein loss.

GeneReviews OMIM ResearchSummary from UniProt

This gene is a member of the muscleblind protein family which was initially described in Drosophila melanogaster. This gene encodes a C3H-type zinc finger protein that modulates alternative splicing of pre-mRNAs. Muscleblind proteins bind specifically to expanded dsCUG RNA but not to normal size CUG repeats and may thereby play a role in the pathophysiology of myotonic dystrophy. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. [provided by RefSeq, Mar 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Mechanism· predicted

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GeneReview available — MBNL2

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in MBNL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 300

381 rare PASS variants

Rare truncating (LoF)

1 in 7,900

34 rare PASS variants

Rare synonymous (reference)

1 in 170

207 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MBNL2. 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)	~556k	1 in 340	1 in 6,500
South Asian	~43k	1 in 260	1 in 6,000
Remaining (unassigned)	~30k	1 in 340	1 in 950
European (Finnish)	~27k	1 in 510	≈ 1 in 27,000
Admixed American	~22k	1 in 180	≈ 1 in 11,000
African / African American	~21k	1 in 400	≈ 1 in 17,000
East Asian	~20k	1 in 180	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 2,900	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 290	none seen

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): 5 of 8 coding exons well covered in gnomAD exomes; exons 6, 8, 9 marginal. Genomes: all 8.? see exons ↓