MBNL1

Chr 3

muscleblind like splicing regulator 1

Also known as: EXP, MBNL

NCBI Gene: 4154 ENSG00000152601 UniProt: Q9NR56 OMIM: 606516

This gene encodes a member of the muscleblind protein family which was initially described in Drosophila melanogaster. The encoded protein is 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. Mice lacking this gene exhibited muscle abnormalities and cataracts. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. The different isoforms are thought to have different binding specificities and/or splicing activities. [provided by RefSeq, Sep 2015]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDystrophia myotonica 1

UniProtCorneal dystrophy, Fuchs endothelial, 3

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

0.42

LOEUF

LOF

Mechanism· predicted

📖

GeneReview available — MBNL1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.706

Z-score 3.50

OE 0.19 (0.09–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.70Z-score

OE missense 0.50 (0.43–0.58)

114 obs / 228.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.42)

0≤0.351.4

Missense OE?0.50 (0.43–0.58)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 4 / 21.5Missense obs/exp: 114 / 228.7Syn Z: 0.42

Background carrier burden — how many people carry a rare variant somewhere in MBNL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 440

373 rare PASS variants

Rare truncating (LoF)

1 in 4,300

40 rare PASS variants

Rare synonymous (reference)

1 in 250

166 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MBNL1. 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 470	1 in 4,600
South Asian	~43k	1 in 400	1 in 1,800
Remaining (unassigned)	~30k	1 in 460	1 in 6,000
European (Finnish)	~27k	1 in 1,700	none seen
Admixed American	~22k	1 in 290	1 in 3,500
African / African American	~21k	1 in 280	1 in 3,600
East Asian	~20k	1 in 230	none seen
Ashkenazi Jewish	~13k	1 in 1,600	none seen
Middle Eastern	~2,884	1 in 360	≈ 1 in 2,900

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