MBNL3
protein-codingmuscleblind like splicing regulator 3, the group of Zinc fingers CCCH-type
Gene summary
This gene encodes a member of the muscleblind-like family of proteins. The encoded protein may function in regulation of alternative splicing and may play a role in the pathophysiology of myotonic dystrophy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Dec 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~120.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MBNL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001386889.1. 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 | 11 | 11 | ||||
| missense | 62 | 1 | 63 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 12 | 12 | ||||
| Total | 0 | 0 | 87 | 1 | 0 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001373818.1 | 8 | MANE Select | |
| Ensembl | ENSP00000359890.3 | 8 | MANE Select | |
| RefSeq | NP_001164172.2 | 7 | Standard | |
| RefSeq | NP_001164173.2 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- regulation of transcription by RNA polymerase II
- mRNA processing
- multicellular organism development
- RNA splicing
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA binding
- protein binding
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370853
- Coding exons
- 8
- Length
- 120652
- Individuals with no LoFs
- 123142
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 2
- Defined
- 123145
- p
- 0.0000122
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.39 | 102 | 150 | 0.681 | 0.0000120 | 2300 |
| Missense (PolyPhen) | 28 | 62.137 | 0.45062 | 865 | ||
| Synonymous | 1.96 | 35 | 53.1 | 0.659 | 0.00000443 | 726 |
| Loss of Function | 2.75 | 2 | 12.5 | 0.160 | 0.00000104 | 188 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000077 | 0.000063 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000074 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000012 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. May play a role in myotonic dystrophy pathophysiology (DM). Could inhibit terminal muscle differentiation, acting at approximately the time of myogenin induction. {ECO:0000269|PubMed:12297108, ECO:0000269|PubMed:15257297}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.129
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.614
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |