MAML1

protein-coding

mastermind like transcriptional coactivator 1

Gene summary

This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate determination. There is in vitro evidence that the human homolog forms a complex with the intracellular portion of human Notch receptors and can increase expression of a Notch-induced gene. This evidence supports its proposed function as a transcriptional co-activator in the Notch signaling pathway. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014757.5

Inheritance

—

ClinVar variants

U:161B:14

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr5:179,732,822-179,777,283

External References & Databases

Ensembl (ENSG00000161021)

Transcript & Mutation Effects

hg38 • Region Span ~44.5 kb

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GenCC 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 MAML1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 161

not providedTotal: 11

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014757.5. 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			2 clinvar	4 clinvar	1 clinvar	7
missense			158 clinvar	8 clinvar	1 clinvar	167
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	161	12	2	175

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014757.5	RefSeq	NP_055572.1	5	MANE Select
ENST00000292599.4	Ensembl	ENSP00000292599.3	5	MANE Select
ENST00000933871.1	Ensembl	ENSP00000603930.1	5	Standard
ENST00000933871.2	Ensembl	ENSP00000603930.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

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

Molecular Function

transcription coactivator activity
protein binding
protein kinase binding
peptide antigen binding

Cellular Component

MAML1-RBP-Jkappa- ICN1 complex
nucleus
nucleoplasm
nuclear speck
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000292599
Coding exons: 5
Length: 63662
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125707
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.481	518	550	0.942	0.0000305	6612
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.0248
RVIS EVS: 0.23
RVIS percentile EVS: 68.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium