MAML1

mastermind like transcriptional coactivator 1

Basic information

Region (hg38): 5:179732821-179777283

Links

ENSG00000161021

∙ NCBI:9794 ∙ OMIM:605424 ∙ HGNC:13632 ∙ Uniprot:Q92585 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAML1 gene.

Inborn genetic diseases (47 variants)
not provided (9 variants)

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 clinvar		4
missense			44 clinvar	4 clinvar	3 clinvar	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region ? Intron variants in splice region, excluding donor/acceptor (+/-2bp)					1	1
non coding ? UTR, intron and other, non coding variants						0
Total	0	0	44	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	Phenotype	Significance	ClinVar
5-179733170-A-G	not specified	Uncertain significance (Dec 26, 2023)	3122402
5-179733273-A-G	not specified	Uncertain significance (Sep 29, 2023)	3122392
5-179733291-A-C	not specified	Uncertain significance (Aug 19, 2023)	2601708
5-179733303-T-C	not specified	Uncertain significance (Aug 11, 2022)	2306405
5-179733353-A-C	not specified	Likely benign (Jun 23, 2021)	2344167
5-179733363-C-T	not specified	Uncertain significance (Dec 19, 2022)	2408561
5-179733374-C-A	not specified	Uncertain significance (Oct 06, 2021)	2352648
5-179733374-C-G	not specified	Likely benign (Nov 18, 2022)	2327455
5-179733381-C-G	not specified	Uncertain significance (Jun 30, 2022)	2299613
5-179733401-G-C		Benign (Dec 31, 2019)	769312
5-179733425-A-G	not specified	Likely benign (Jun 26, 2023)	2601666
5-179765340-A-G		Likely benign (Apr 01, 2022)	2656134
5-179765351-A-C	not specified	Uncertain significance (Aug 11, 2022)	2306457
5-179765363-C-T	not specified	Uncertain significance (Jul 16, 2021)	2238126
5-179765400-C-T		Likely benign (Apr 01, 2022)	2656135
5-179765461-T-C	not specified	Uncertain significance (Sep 13, 2023)	2623792
5-179765465-C-G	not specified	Uncertain significance (Jun 24, 2022)	2400629
5-179765492-T-G	not specified	Uncertain significance (Sep 14, 2022)	2311801
5-179765504-A-T	not specified	Uncertain significance (Nov 05, 2021)	2390219
5-179765579-G-A		Likely benign (Mar 01, 2023)	717077
5-179765621-C-G	not specified	Uncertain significance (Jan 26, 2023)	2457212
5-179765673-C-T		Likely benign (Apr 01, 2022)	2656136
5-179765728-C-T	not specified	Uncertain significance (Dec 14, 2023)	3122403
5-179765744-A-G	not specified	Uncertain significance (Jul 25, 2023)	2590144
5-179765915-T-G	not specified	Uncertain significance (Aug 13, 2021)	2244815

GnomAD

Source: gnomAD

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: dbNSFP

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