MAML2

mastermind like transcriptional coactivator 2

Basic information

Region (hg38): 11:95976597-96343195

Links

ENSG00000184384 ∙ NCBI:84441 ∙ OMIM:607537 ∙ HGNC:16259 ∙ Uniprot:Q8IZL2 ∙ 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 MAML2 gene.

• Inborn genetic diseases (38 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAML2 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				1		1
missense			38		1	39
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	38	1	1

Variants in MAML2

This is a list of pathogenic ClinVar variants found in the MAML2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-95979125-T-G		not specified	Uncertain significance (Aug 08, 2023)
11-95979147-T-G		not specified	Uncertain significance (Dec 12, 2023)
11-95979198-G-A		not specified	Uncertain significance (Jun 02, 2023)
11-95979204-G-C		not specified	Uncertain significance (Nov 07, 2023)
11-95979245-A-C		not specified	Uncertain significance (Nov 17, 2022)
11-95979292-G-T		not specified	Uncertain significance (Jul 13, 2022)
11-95979301-T-C		not specified	Uncertain significance (Oct 05, 2023)
11-95979394-A-C			Uncertain significance (-)
11-95979465-C-T		not specified	Uncertain significance (May 13, 2022)
11-95979472-C-G		not specified	Uncertain significance (Aug 02, 2021)
11-95979495-T-C		not specified	Uncertain significance (Oct 04, 2022)
11-95979528-G-T		not specified	Uncertain significance (Feb 28, 2024)
11-95979556-C-T		not specified	Uncertain significance (Feb 02, 2024)
11-95979588-A-G		not specified	Uncertain significance (May 08, 2023)
11-95979667-T-C		not specified	Uncertain significance (Apr 12, 2022)
11-95979677-T-A		not specified	Uncertain significance (Apr 20, 2023)
11-95979834-G-A		not specified	Uncertain significance (Oct 17, 2023)
11-95979859-C-G		not specified	Uncertain significance (Apr 19, 2023)
11-95979921-G-A		not specified	Uncertain significance (Jun 23, 2021)
11-95985591-G-A		not specified	Uncertain significance (Nov 27, 2023)
11-95985611-C-T		not specified	Uncertain significance (Jun 27, 2022)
11-95991555-G-C		not specified	Uncertain significance (Jun 06, 2023)
11-95991594-T-C		not specified	Uncertain significance (Apr 17, 2023)
11-95991644-C-G		not specified	Uncertain significance (Oct 25, 2022)
11-95991668-C-G		not specified	Uncertain significance (Dec 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAML2	protein_coding	protein_coding	ENST00000524717	5	366583

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000131	124671	0	9	124680	0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.450	584	615	0.949	0.0000309	7580
Missense in Polyphen		97	95.577	1.0149		1123
Synonymous	-0.755	249	234	1.06	0.0000122	2261
Loss of Function	5.91	6	51.9	0.116	0.00000273	487

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000647	0.0000619
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
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. Potentiates activation by NOTCH3 and NOTCH4 more efficiently than MAML1 or MAML3. {ECO:0000269|PubMed:12370315, ECO:0000269|PubMed:12386158, ECO:0000269|PubMed:12539049}.
• Disease: DISEASE: Note=A chromosomal aberration involving MAML2 is found in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. Translocation t(11;19)(q21;p13) with CRTC1. The fusion protein consists of the N-terminus of CRTC1 joined to the C-terminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the C-terminus of CRTC1 has been detected in a small number of mucoepidermoid carcinomas. {ECO:0000269|PubMed:15729701}.
• Pathway: Th1 and Th2 cell differentiation - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);NOTCH-Ncore;Canonical and Non-canonical Notch signaling;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: 0.134

Intolerance Scores

• rvis_EVS: 0.21
• rvis_percentile_EVS: 67.52

Haploinsufficiency Scores

• pHI: 0.287
• hipred: N
• hipred_score: 0.314
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Maml2

Gene ontology

• 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
• Cellular component: nucleus;nucleoplasm;nuclear speck
• Molecular function: transcription coactivator activity