MLXIPL

protein-coding

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

Gene summary

This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Previous symbols:

WBSCR14

MANE transcript

NM_032951.3

Inheritance

—

ClinVar variants

U:127B:57

Top phenotype

Williams syndrome

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr7:73,593,194-73,624,543

External References & Databases

Ensembl (ENSG00000009950)

Transcript & Mutation Effects

hg38 • Region Span ~31.3 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 MLXIPL variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 55

Williams syndromeTotal: 2

MLXIPL-related disorderTotal: 1

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032951.3. 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				25 clinvar	6 clinvar	31
missense			122 clinvar	19 clinvar	7 clinvar	148
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	127	44	13	184

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032951.3	RefSeq	NP_116569.1	17	MANE Select
ENST00000313375.8	Ensembl	ENSP00000320886.3	17	MANE Select
NM_032952.3	RefSeq	NP_116570.1	17	Standard
NM_032953.3	RefSeq	NP_116571.1	17	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)
Metformin Pathway, Pharmacodynamic
Angiopoietin Like Protein 8 Regulatory Pathway
Liver steatosis AOP

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription, DNA-templated
regulation of transcription by RNA polymerase II
positive regulation of cell population proliferation
anatomical structure morphogenesis

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity
transcription factor binding

Cellular Component

nucleus
nucleoplasm
transcription factor complex
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313375
Coding exons: 17
Length: 31350
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.23	391	466	0.839	0.0000298	5359
Missense (PolyPhen)		162	190.92	0.84853		2234
Synonymous	0.891	179	195	0.919	0.0000121	1804
Loss of Function	3.90	9	33.2	0.271	0.00000161	381

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000082	0.000062	rare
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)	0.00010	0.000097	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor. Binds to the canonical and non-canonical E box sequences 5'-CACGTG-3' (By similarity). {ECO:0000250}.;
Disease: DISEASE: Note=WBSCR14 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of WBSCR14 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. {ECO:0000269|PubMed:10780788}.;

Intolerance Scores

LoFtool: 0.427
RVIS EVS: 0.6
RVIS percentile EVS: 82.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

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