MBNL1

Chr 3

muscleblind like splicing regulator 1

Also known as: EXP, MBNL

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]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.42
Clinical SummaryMBNL1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
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ClinVar Variants
30 VUS of 64 total submissions
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GeneReview available — MBNL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.42LOEUF
pLI 0.706
Z-score 3.50
OE 0.19 (0.090.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.70Z-score
OE missense 0.50 (0.430.58)
114 obs / 228.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.19 (0.090.42)
00.351.4
Missense OE?0.50 (0.430.58)
00.61.4
Synonymous OE?0.94
01.21.6
LoF obs/exp: 4 / 21.5Missense obs/exp: 114 / 228.7Syn Z: 0.42

This gene — mechanism propensity

DN
0.5180th %ile
GOF
0.5268th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.42

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

64 submitted variants in ClinVar

Classification Summary

VUS30
Likely Benign6
Benign2
30
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
29
0
0
30
Likely Benign
0
3
2
1
6
Benign
0
0
1
1
2
Total1323238

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap MBNL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MBNL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →