MAML1
mastermind like transcriptional coactivator 1
Basic information
Region (hg38): 5:179732822-179777283
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 MAML1 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 | 4 | |||||
| missense | 64 | 71 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 64 | 8 | 3 |
Variants in MAML1
This is a list of pathogenic ClinVar variants found in the MAML1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-179733158-C-A | not specified | Uncertain significance (Sep 08, 2024) | ||
| 5-179733170-A-G | not specified | Uncertain significance (Dec 26, 2023) | ||
| 5-179733273-A-G | not specified | Uncertain significance (Sep 29, 2023) | ||
| 5-179733291-A-C | not specified | Uncertain significance (Aug 19, 2023) | ||
| 5-179733303-T-C | not specified | Uncertain significance (Aug 11, 2022) | ||
| 5-179733353-A-C | not specified | Likely benign (Jun 23, 2021) | ||
| 5-179733363-C-T | not specified | Uncertain significance (Dec 19, 2022) | ||
| 5-179733374-C-A | not specified | Uncertain significance (Oct 06, 2021) | ||
| 5-179733374-C-G | not specified | Likely benign (Nov 18, 2022) | ||
| 5-179733381-C-G | not specified | Uncertain significance (Jun 30, 2022) | ||
| 5-179733401-G-C | Benign (Dec 31, 2019) | |||
| 5-179733425-A-G | not specified | Likely benign (Jun 26, 2023) | ||
| 5-179765333-A-G | not specified | Uncertain significance (Oct 17, 2024) | ||
| 5-179765340-A-G | Likely benign (Apr 01, 2022) | |||
| 5-179765351-A-C | not specified | Uncertain significance (Aug 11, 2022) | ||
| 5-179765363-C-T | not specified | Uncertain significance (Jul 16, 2021) | ||
| 5-179765365-A-G | not specified | Uncertain significance (Aug 05, 2024) | ||
| 5-179765400-C-T | Likely benign (Apr 01, 2022) | |||
| 5-179765435-G-A | not specified | Uncertain significance (Jun 19, 2024) | ||
| 5-179765461-T-C | not specified | Uncertain significance (Sep 13, 2023) | ||
| 5-179765465-C-G | not specified | Uncertain significance (Jun 24, 2022) | ||
| 5-179765492-T-G | not specified | Uncertain significance (Sep 14, 2022) | ||
| 5-179765494-G-A | not specified | Uncertain significance (Aug 28, 2024) | ||
| 5-179765504-A-T | not specified | Uncertain significance (Nov 05, 2021) | ||
| 5-179765528-T-C | not specified | Uncertain significance (Apr 17, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAML1 | protein_coding | protein_coding | ENST00000292599 | 5 | 63662 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000472 | 125705 | 0 | 2 | 125707 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.481 | 518 | 550 | 0.942 | 0.0000305 | 6612 |
| Missense in Polyphen | 129 | 144.12 | 0.89507 | 1817 | ||
| Synonymous | 0.477 | 231 | 240 | 0.961 | 0.0000151 | 2119 |
| Loss of Function | 5.13 | 1 | 32.6 | 0.0307 | 0.00000156 | 329 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000291 | 0.0000291 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000880 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662, ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:17317671}.;
- Pathway
- Th1 and Th2 cell differentiation - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Notch Signaling Pathway;Canonical and Non-canonical Notch signaling;Notch Signaling Pathway;Notch Signaling Pathway;Notch;Disease;RUNX3 regulates NOTCH signaling;Signal Transduction;Gene expression (Transcription);Transcriptional regulation by RUNX3;Generic Transcription Pathway;RNA Polymerase II Transcription;Notch-HLH transcription pathway;Notch;NICD traffics to nucleus;Pre-NOTCH Transcription and Translation;Pre-NOTCH Expression and Processing;Signaling by NOTCH1;NOTCH2 intracellular domain regulates transcription;Signaling by NOTCH2;NOTCH3 Intracellular Domain Regulates Transcription;Signaling by NOTCH3;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;Notch signaling pathway;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;BMP2 signaling TGF-beta MV;BMP signaling Dro;Notch-mediated HES/HEY network;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription
(Consensus)
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- loftool
- 0.0248
- rvis_EVS
- 0.23
- rvis_percentile_EVS
- 68.57
Haploinsufficiency Scores
- pHI
- 0.568
- hipred
- Y
- hipred_score
- 0.711
- ghis
- 0.529
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Maml1
- Phenotype
- 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); immune system phenotype; embryo phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; 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); hematopoietic system phenotype; 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); craniofacial phenotype; muscle phenotype; cellular phenotype;
Gene ontology
- Biological process
- atrioventricular node development;transcription initiation from RNA polymerase II promoter;protein phosphorylation;Notch signaling pathway;positive regulation of transcription of Notch receptor target;positive regulation of myotube differentiation;myoblast differentiation;positive regulation of Notch signaling pathway;positive regulation of transcription by RNA polymerase II;atrioventricular node cell development
- Cellular component
- MAML1-RBP-Jkappa- ICN1 complex;nucleus;nucleoplasm;nuclear speck;intracellular membrane-bounded organelle
- Molecular function
- transcription coactivator activity;protein binding;protein kinase binding;peptide antigen binding