MGA

protein-coding

MAX dimerization protein MGA, the group of MAX dimerization proteins|MicroRNA protein coding host genes|T-box transcription factors

Gene summary

Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell fate specification and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Part of MLL1 complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001400225.1

Inheritance

ClinVar variants

P:4U:67B:20

Top phenotype

Premature ovarian failure 26

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr15:41,621,134-41,773,081

External References & Databases

Ensembl (ENSG00000174197)

Transcript & Mutation Effects

hg38 • Region Span ~151.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Premature ovarian failure 26AD

Manifestation: Endocrine; Obstetric

Intervention: Obstetric

Rationale: Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency

Refs: 39545409

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MGA variants in ClinVar

5 Conditions Cataloged

not providedTotal: 41

not specifiedTotal: 21

Premature ovarian failure 26Total: 3

MGA related disorderTotal: 3

Multiple myelomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001400225.1. 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			4 clinvar	6 clinvar	3 clinvar	13
missense		1 clinvar	48 clinvar	6 clinvar	5 clinvar	60
nonsense	1 clinvar		7 clinvar			8
start loss						0
frameshift	2 clinvar		3 clinvar			5
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	3	1	67	12	8	91

Highest pathogenic variant AF is 0.0000013682867

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001400225.1	RefSeq	NP_001387154.1	23	MANE Select
ENST00000703841.1	Ensembl	ENSP00000515495.1	23	MANE Select
NM_001080541.3	RefSeq	NP_001074010.2	22	Standard
NM_001164273.2	RefSeq	NP_001157745.1	23	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mgaa	Danio rerio	Structure: forebrain midbrain boundary Quality: amorphous abnormal

Gene / Model

Organism

Observed Phenotype

mgaa

Danio rerio

Structure: forebrain midbrain boundary

Quality: amorphous

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pathways Affected in Adenoid Cystic Carcinoma
Gene expression (Transcription)
Transcriptional Regulation by E2F6
Generic Transcription Pathway
RNA Polymerase II Transcription

Biological Process

regulation of transcription by RNA polymerase II
negative regulation of G0 to G1 transition

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
protein binding
protein dimerization activity

Cellular Component

nucleoplasm
MLL1 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219905
Coding exons: 23
Length: 148720
Individuals with no LoFs: 124639
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 124652
p: 0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	1431	1.55e+3	0.921	0.0000792	19933
Missense (PolyPhen)		330	521.81	0.63241		6663
Synonymous	-0.111	564	561	1.01	0.0000274	6155
Loss of Function	9.58	5	117	0.0428	0.00000690	1480

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000058	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00010	0.000093	rare
European (Non-Finnish)	0.000046	0.000044	rare
South Asian	0.00013	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a dual-specificity transcription factor, regulating the expression of both MAX-network and T-box family target genes. Functions as a repressor or an activator. Binds to 5'-AATTTCACACCTAGGTGTGAAATT-3' core sequence and seems to regulate MYC-MAX target genes. Suppresses transcriptional activation by MYC and inhibits MYC-dependent cell transformation. Function activated by heterodimerization with MAX. This heterodimerization serves the dual function of both generating an E-box-binding heterodimer and simultaneously blocking interaction of a corepressor (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.00847
RVIS EVS: -0.61
RVIS percentile EVS: 17.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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