MBNL1
muscleblind like splicing regulator 1, the group of Zinc fingers CCCH-type
Basic information
Region (hg38): 3:152243828-152465780
Previous symbols: [ "MBNL" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MBNL1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 10 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 3 | |||||
| Total | 0 | 0 | 8 | 5 | 2 |
Variants in MBNL1
This is a list of pathogenic ClinVar variants found in the MBNL1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-152268473-C-T | not specified | Benign (Jul 10, 2015) | ||
| 3-152300313-G-A | MBNL1-related disorder | Benign (Feb 20, 2019) | ||
| 3-152432745-C-T | not specified | Uncertain significance (Jan 03, 2024) | ||
| 3-152432760-C-T | not specified | Uncertain significance (Nov 09, 2021) | ||
| 3-152432765-G-A | not specified | Uncertain significance (Jul 19, 2022) | ||
| 3-152432853-C-T | not specified | Uncertain significance (Apr 07, 2022) | ||
| 3-152445316-G-A | not specified | Uncertain significance (May 30, 2024) | ||
| 3-152445423-C-T | not specified | Uncertain significance (Aug 02, 2021) | ||
| 3-152445526-C-A | not specified | Uncertain significance (Aug 02, 2021) | ||
| 3-152447678-A-G | not specified | Uncertain significance (Sep 26, 2022) | ||
| 3-152447688-C-T | MBNL1-related disorder | Likely benign (Sep 17, 2019) | ||
| 3-152456289-G-A | MBNL1-related disorder | Likely benign (Feb 19, 2019) | ||
| 3-152456304-C-T | not specified | Likely benign (Oct 14, 2023) | ||
| 3-152456338-G-A | not specified | Uncertain significance (Jul 14, 2023) | ||
| 3-152458124-C-T | Likely benign (Nov 01, 2023) | |||
| 3-152459328-A-T | MBNL1-related disorder | Likely benign (Jun 26, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MBNL1 | protein_coding | protein_coding | ENST00000282486 | 8 | 221953 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.706 | 0.294 | 125727 | 0 | 4 | 125731 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.70 | 114 | 229 | 0.498 | 0.0000126 | 2507 |
| Missense in Polyphen | 52 | 108.98 | 0.47715 | 1226 | ||
| Synonymous | 0.424 | 81 | 86.0 | 0.942 | 0.00000522 | 790 |
| Loss of Function | 3.50 | 4 | 21.5 | 0.186 | 0.00000133 | 217 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000995 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000272 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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. Regulates the TNNT2 exon 5 skipping through competition with U2AF2. Inhibits the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA. Binds to the stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Binds to the 5'-YGCU(U/G)Y- 3'consensus sequence. Binds to the IR RNA. Binds to expanded CUG repeat RNA, which folds into a hairpin structure containing GC base pairs and bulged, unpaired U residues. {ECO:0000269|PubMed:10970838, ECO:0000269|PubMed:15257297, ECO:0000269|PubMed:16946708, ECO:0000269|PubMed:18335541, ECO:0000269|PubMed:19470458}.;
- Disease
- DISEASE: Corneal dystrophy, Fuchs endothelial, 3 (FECD3) [MIM:613267]: A late-onset form of Fuchs endothelial corneal dystrophy, a disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition. {ECO:0000269|PubMed:25593321}. Note=The protein represented in this entry is involved in disease pathogenesis. In corneal endothelial cells from patients, MBNL1 is sequestered by TCF4 RNAs containing pathogenic CUG triplet repeat expansions. This results in missplicing of essential MBNL1-regulated mRNAs. {ECO:0000269|PubMed:25593321}.;
- Pathway
- miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Adipogenesis
(Consensus)
Recessive Scores
- pRec
- 0.250
Intolerance Scores
- loftool
- 0.159
- rvis_EVS
- -0.45
- rvis_percentile_EVS
- 24
Haploinsufficiency Scores
- pHI
- 0.823
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.681
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.967
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mbnl1
- Phenotype
- growth/size/body region phenotype; muscle phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype;
Gene ontology
- Biological process
- regulation of alternative mRNA splicing, via spliceosome;in utero embryonic development;mRNA processing;nervous system development;RNA splicing;embryonic limb morphogenesis;regulation of RNA splicing;myoblast differentiation
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;cytoplasmic stress granule
- Molecular function
- regulatory region RNA binding;RNA binding;double-stranded RNA binding;protein binding;metal ion binding