MAML3

protein-coding

mastermind like transcriptional coactivator 3

Gene summary

Enables transcription coactivator activity. Involved in Notch signaling pathway and positive regulation of transcription by RNA polymerase II. Located in nuclear speck. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

TNRC3

MANE transcript

NM_018717.5

Inheritance

—

ClinVar variants

U:86B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr4:139,716,753-140,154,184

External References & Databases

Ensembl (ENSG00000196782)

Transcript & Mutation Effects

hg38 • Region Span ~437.4 kb

Loading mutation effect viewer...

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 MAML3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018717.5. 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			3 clinvar	3 clinvar		6
missense			81 clinvar	1 clinvar		82
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	86	4	0	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018717.5	RefSeq	NP_061187.3	5	MANE Select
ENST00000509479.6	Ensembl	ENSP00000421180.1	5	MANE Select
ENST00000502696.1	Ensembl	ENSP00000422783.1	4	Standard
ENST00000899537.1	Ensembl	ENSP00000569596.1	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-Ncore
Notch Signaling Pathway

Biological Process

transcription initiation from RNA polymerase II promoter
Notch signaling pathway
positive regulation of transcription of Notch receptor target
positive regulation of Notch signaling pathway
positive regulation of transcription by RNA polymerase II

Molecular Function

transcription coactivator activity

Cellular Component

nucleus
nucleoplasm
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000509479
Coding exons: 5
Length: 437432
Individuals with no LoFs: 22445
Homozygous LoFs: 71581
Heterozygous LoFs: 31229
Defined: 125255
p: 0.577

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.902	573	637	0.899	0.0000340	7480
Missense (PolyPhen)		178	213.07	0.83542		2575
Synonymous	1.19	233	257	0.906	0.0000154	2238
Loss of Function	5.68	5	47.0	0.106	0.00000248	423

Population LoF Frequency

Population	CAF	p-value	Status
African	0.83	0.32	notable
Latino/Admixed American	1.3	0.57	notable
Ashkenazi Jewish	1.5	0.66	notable
East Asian	1.2	0.52	notable
Finnish	1.6	0.64	notable
European (Non-Finnish)	1.6	0.59	notable
South Asian	1.5	0.69	notable
Other	1.5	0.61	notable

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. {ECO:0000269|PubMed:12370315, ECO:0000269|PubMed:12386158}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.595
RVIS EVS: 0.03
RVIS percentile EVS: 55.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.979

Gene Damage Prediction

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