MLX

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

Basic information

Region (hg38): 17:42567072-42573239

Previous symbols: [ "TCFL4" ]

Links

ENSG00000108788 ∙ NCBI:6945 ∙ OMIM:602976 ∙ HGNC:11645 ∙ Uniprot:Q9UH92 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MLX gene.

• Ovarian dysgenesis 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MLX gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	1	4
missense			14		1	15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding	1		2	1	1	5
Total	1	0	16	4	3

Variants in MLX

This is a list of pathogenic ClinVar variants found in the MLX region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-42567146-C-A		not specified	Uncertain significance (Dec 13, 2023)
17-42567190-C-T			Likely benign (Nov 15, 2017)
17-42567232-C-T			Likely benign (Nov 09, 2017)
17-42567251-C-T		not specified	Uncertain significance (Jan 30, 2024)
17-42567257-T-C		not specified	Uncertain significance (Aug 30, 2022)
17-42567284-C-T		not specified	Uncertain significance (May 24, 2024)
17-42567651-C-T			Benign (Jul 02, 2018)
17-42568473-T-A		not specified	Uncertain significance (May 03, 2023)
17-42568482-A-G		not specified	Uncertain significance (Jan 06, 2023)
17-42568488-C-T		not specified	Uncertain significance (Oct 16, 2023)
17-42568490-C-T		not specified	Uncertain significance (Apr 25, 2023)
17-42568494-A-G		not specified	Uncertain significance (Aug 17, 2022)
17-42568525-C-T			Likely benign (Dec 13, 2017)
17-42568526-G-A		not specified	Uncertain significance (Dec 14, 2022)
17-42568530-C-T		not specified	Uncertain significance (Jun 29, 2023)
17-42568832-C-T			Likely benign (Dec 22, 2017)
17-42569595-G-C		not specified	Uncertain significance (Dec 18, 2023)
17-42570011-A-G			Benign (Jul 13, 2018)
17-42570027-A-C		not specified	Uncertain significance (Sep 22, 2021)
17-42570104-A-G		not specified	Uncertain significance (Apr 24, 2024)
17-42571563-T-C		not specified	Uncertain significance (Feb 13, 2024)
17-42571566-T-G		not specified	Uncertain significance (Sep 14, 2023)
17-42572959-G-A			Benign (May 30, 2020)
17-42572976-C-T		PSMC3IP-related disorder	Likely benign (Mar 20, 2024)
17-42572988-C-A		not specified	Uncertain significance (Jun 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MLX	protein_coding	protein_coding	ENST00000246912	8	6172

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.110	0.884	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.476	136	153	0.892	0.00000885	1946
Missense in Polyphen		39	58.682	0.66459		725
Synonymous	-0.127	61	59.8	1.02	0.00000338	554
Loss of Function	2.42	4	13.6	0.294	5.81e-7	179

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000454	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription regulator. Forms a sequence-specific DNA- binding protein complex with MAD1, MAD4, MNT, WBSCR14 and MLXIP which recognizes the core sequence 5'-CACGTG-3'. The TCFL4-MAD1, TCFL4-MAD4, TCFL4-WBSCR14 complexes are transcriptional repressors. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation. {ECO:0000269|PubMed:10593926, ECO:0000269|PubMed:12446771, ECO:0000269|PubMed:16782875}.
• Pathway: Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Metabolism;ChREBP activates metabolic gene expression;Integration of energy metabolism (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.290
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

• pHI: 0.0499
• hipred: Y
• hipred_score: 0.699
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.984

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mlx

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;nuclear membrane
• 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;DNA-binding transcription factor activity;protein binding;transcription factor binding;protein homodimerization activity;protein heterodimerization activity