MLXIP

protein-coding

MLX interacting protein, the group of Basic helix-loop-helix proteins

Gene summary

This gene encodes a protein that functions as part of a heterodimer to activate transcription. The encoded protein forms a heterodimer with Max-like protein X (MLX) and is involved in the regulation of genes in response to cellular glucose levels. [provided by RefSeq, Mar 2014]

MANE transcript

NM_014938.6

Inheritance

—

ClinVar variants

U:55

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr12:122,078,756-122,147,344

External References & Databases

Ensembl (ENSG00000175727)

Transcript & Mutation Effects

hg38 • Region Span ~68.6 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 MLXIP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014938.6. 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
missense			49 clinvar			49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	55	0	0	55

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014938.6	RefSeq	NP_055753.3	17	MANE Select
ENST00000319080.12	Ensembl	ENSP00000312834.6	17	MANE Select
ENST00000366272.6	Ensembl	ENSP00000445891.1	6	Standard
ENST00000535430.5	Ensembl	ENSP00000438206.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin resistance - Homo sapiens (human)
Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)

Biological Process

regulation of transcription by RNA polymerase II
positive regulation of transcription by RNA polymerase II
regulation of carbohydrate metabolic process by regulation of transcription from RNA polymerase II promoter

Molecular Function

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

Cellular Component

nucleus
mitochondrial outer membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000319080
Coding exons: 17
Length: 115267
Individuals with no LoFs: 124654
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 124660
p: 0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.25	377	521	0.723	0.0000318	5922
Missense (PolyPhen)		88	181.91	0.48375		2220
Synonymous	-0.492	236	227	1.04	0.0000152	1873
Loss of Function	4.76	5	35.7	0.140	0.00000153	427

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds DNA as a heterodimer with MLX and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation. {ECO:0000250|UniProtKB:Q2VPU4, ECO:0000269|PubMed:12446771, ECO:0000269|PubMed:16782875}.;

Recessive Scores

pRec: 0.111

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.698

Gene Damage Prediction

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