MXI1

protein-coding

MAX interactor 1, dimerization protein, the group of Basic helix-loop-helix proteins|MAX dimerization proteins

Gene summary

Expression of the c-myc gene, which produces an oncogenic transcription factor, is tightly regulated in normal cells but is frequently deregulated in human cancers. The protein encoded by this gene is a transcriptional repressor thought to negatively regulate MYC function, and is therefore a potential tumor suppressor. This protein inhibits the transcriptional activity of MYC by competing for MAX, another basic helix-loop-helix protein that binds to MYC and is required for its function. Defects in this gene are frequently found in patients with prostate tumors. Three alternatively spliced transcripts encoding different isoforms have been described. Additional alternatively spliced transcripts may exist but the products of these transcripts have not been verified experimentally. [provided by RefSeq, Jul 2008]

MANE transcript

NM_130439.3

Inheritance

—

ClinVar variants

P:6U:53B:6

Top phenotype

MXI1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr10:110,207,605-110,287,365

External References & Databases

Ensembl (ENSG00000119950)

Transcript & Mutation Effects

hg38 • Region Span ~79.8 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 MXI1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 48

MXI1-related disorderTotal: 5

Prostate cancerTotal: 3

Ovarian cancerTotal: 3

not providedTotal: 1

NeurofibrosarcomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_130439.3. 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	2 clinvar	1 clinvar	4
missense	2 clinvar	2 clinvar	49 clinvar	1 clinvar	2 clinvar	56
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	4	2	53	3	3	65

Highest pathogenic variant AF is 0.000024781397

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_130439.3	RefSeq	NP_569157.2	6	MANE Select
ENST00000332674.9	Ensembl	ENSP00000331152.5	6	MANE Select
NM_001008541.1	RefSeq	NP_001008541.1	4	Standard
NM_005962.5	RefSeq	NP_005953.4	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hematopoietic Stem Cell Differentiation

Biological Process

negative regulation of transcription by RNA polymerase II
negative regulation of cell population proliferation
cytoplasmic sequestering of transcription factor

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
DNA binding
transcription corepressor activity

Cellular Component

nucleus
nucleolus
cytosol
RNA polymerase II transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332674
Coding exons: 6
Length: 79761
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.17	114	155	0.736	0.00000872	1909
Missense (PolyPhen)		40	71.183	0.56193		852
Synonymous	-0.0137	59	58.9	1.00	0.00000316	578
Loss of Function	2.29	8	18.7	0.428	0.00000150	163

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000061	0.000058	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor. MXI1 binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. MXI1 thus antagonizes MYC transcriptional activity by competing for MAX.;

Recessive Scores

pRec: 0.181

Intolerance Scores

LoFtool: 0.531
RVIS EVS: -0.21
RVIS percentile EVS: 38.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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