MXD3

protein-coding

MAX dimerization protein 3, the group of Basic helix-loop-helix proteins|MAX dimerization proteins

Gene summary

This gene encodes a member of the Myc superfamily of basic helix-loop-helix leucine zipper transcriptional regulators. The encoded protein forms a heterodimer with the cofactor MAX which binds specific E-box DNA motifs in the promoters of target genes and regulates their transcription. Disruption of the MAX-MXD3 complex is associated with uncontrolled cell proliferation and tumorigenesis. Transcript variants of this gene encoding different isoforms have been described.[provided by RefSeq, Dec 2008]

MANE transcript

NM_031300.4

Inheritance

—

ClinVar variants

U:37B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr5:177,301,461-177,312,757

External References & Databases

Ensembl (ENSG00000213347)

Transcript & Mutation Effects

hg38 • Region Span ~11.3 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 MXD3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 39

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031300.4. 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				1 clinvar		1
missense			35 clinvar	4 clinvar		39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	37	5	0	42

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031300.4	RefSeq	NP_112590.1	6	MANE Select
ENST00000439742.7	Ensembl	ENSP00000401867.2	6	MANE Select
NM_001142935.2	RefSeq	NP_001136407.1	6	Standard
NM_001394986.1	RefSeq	NP_001381915.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
protein binding
protein dimerization activity

Cellular Component

RNA polymerase II transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000439742
Coding exons: 6
Length: 11297
Individuals with no LoFs: 125674
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125696
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.194	120	126	0.951	0.00000896	1280
Missense (PolyPhen)		44	49.386	0.89094		522
Synonymous	-1.66	72	56.2	1.28	0.00000355	424
Loss of Function	1.15	5	8.64	0.579	3.66e-7	118

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000090	0.000088	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor. Binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. Antagonizes MYC transcriptional activity by competing for MAX and suppresses MYC dependent cell transformation (By similarity). {ECO:0000250}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.963

Gene Damage Prediction

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