MAX

MYC associated factor X, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 14:65006173-65102695

Links

ENSG00000125952 ∙ NCBI:4149 ∙ OMIM:154950 ∙ HGNC:6913 ∙ Uniprot:P61244 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pheochromocytoma (Definitive), mode of inheritance: AD
• hereditary pheochromocytoma-paraganglioma (Supportive), mode of inheritance: AD
• pheochromocytoma (Definitive), mode of inheritance: AD
• pheochromocytoma (Strong), mode of inheritance: AD
• hereditary pheochromocytoma-paraganglioma (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pheochromocytoma	AD	Oncologic	Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of neoplasms, which may may reduce morbidity and mortality	Oncologic	21685915

ClinVar

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

• Hereditary pheochromocytoma-paraganglioma (300 variants)
• Hereditary cancer-predisposing syndrome (199 variants)
• Pheochromocytoma (74 variants)
• not provided (53 variants)
• not specified (13 variants)
• Pheochromocytoma, susceptibility to (4 variants)
• MAX-related condition (3 variants)
• MAX-associated Macrocephaly and Polydactyly syndrome (1 variants)
• Retinoblastoma (1 variants)
• Inborn genetic diseases (1 variants)
• POLYDACTYLY-MACROCEPHALY SYNDROME (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAX 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			1	100		101
missense	3	1	165	8		177
nonsense	8	2	4	1		15
start loss	1					1
frameshift	11	4	3			18
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	1	1			4
splice region			9	14		23
non coding		1	29	50	29	109
Total	25	9	204	159	29

Variants in MAX

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

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

Position	Type	Phenotype	Significance	ClinVar
14-65006243-A-C			Pathogenic (Sep 01, 2023)
14-65006289-G-T		Hereditary cancer-predisposing syndrome • Pheochromocytoma • MAX-related disorder	Likely benign (Jan 24, 2023)
14-65006478-G-A			Benign (Jun 15, 2018)
14-65012397-C-A		not specified	Benign (Aug 15, 2023)
14-65032594-G-A		not specified	Likely benign (Aug 15, 2023)
14-65032676-C-T			Likely benign (Jun 01, 2023)
14-65044403-G-A			Likely benign (Jan 01, 2023)
14-65053272-C-T			Benign (Dec 01, 2023)
14-65075168-G-A		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
14-65075191-A-G		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
14-65075198-G-A		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
14-65075200-C-G		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
14-65075247-G-A		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
14-65075349-C-G		Pheochromocytoma	Benign (Jun 14, 2016)
14-65075353-T-G		Pheochromocytoma	Benign (Jan 13, 2018)
14-65075441-G-A		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
14-65075453-G-A		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
14-65075533-C-T		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
14-65075534-G-A		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
14-65075603-A-G		Pheochromocytoma	Uncertain significance (Jan 13, 2018)
14-65075759-A-G		Pheochromocytoma	Benign (Jun 14, 2016)
14-65075776-C-A		Pheochromocytoma	Benign (Jan 13, 2018)
14-65075798-G-A		Pheochromocytoma	Uncertain significance (Jan 12, 2018)
14-65075860-G-A		Pheochromocytoma	Benign (Jan 13, 2018)
14-65075864-CTG-C		Pheochromocytoma	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAX	protein_coding	protein_coding	ENST00000358664	5	96522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.834	0.166	125739	0	3	125742	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.81	45	94.6	0.476	0.00000616	1064
Missense in Polyphen		10	33.549	0.29807		356
Synonymous	0.560	32	36.3	0.882	0.00000218	288
Loss of Function	2.68	1	10.3	0.0973	6.40e-7	103

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription regulator. Forms a sequence-specific DNA- binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a repressor. May repress transcription via the recruitment of a chromatin remodeling complex containing H3 'Lys-9' histone methyltransferase activity. Represses MYC transcriptional activity from E-box elements. {ECO:0000269|PubMed:26070438}.
• Disease: DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine- producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269|PubMed:21685915, ECO:0000269|PubMed:22452945, ECO:0000269|PubMed:26070438}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Small cell lung cancer - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);EGF-Core;B Cell Receptor Signaling Pathway;Pathways Affected in Adenoid Cystic Carcinoma;MAPK Signaling Pathway;p38 MAPK Signaling Pathway;Gene expression (Transcription);p38 mapk signaling pathway;overview of telomerase protein component gene htert transcriptional regulation;mapkinase signaling pathway;Transcriptional Regulation by E2F6;Generic Transcription Pathway;RNA Polymerase II Transcription;Cyclin E associated events during G1/S transition ;Mitotic G1-G1/S phases;G1/S Transition;C-MYC pathway;Cell Cycle;Cell Cycle, Mitotic;Validated targets of C-MYC transcriptional repression;Validated targets of C-MYC transcriptional activation;Regulation of Telomerase;Signaling events mediated by HDAC Class I;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.573

Intolerance Scores

• loftool: 0.156
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.250
• hipred: Y
• hipred_score: 0.774
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Max
• Phenotype: cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: max
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;cellular response to starvation;response to insulin;positive regulation of transcription by RNA polymerase II;response to axon injury;neuron apoptotic process;retina development in camera-type eye;protein-containing complex assembly;negative regulation of G0 to G1 transition;cellular response to peptide hormone stimulus
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm;PML body;dendrite;protein-DNA complex;MLL1 complex;RNA polymerase II transcription factor complex
• 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;transcription coregulator activity;transcription coactivator activity;protein binding;protein homodimerization activity;protein-containing complex binding;protein heterodimerization activity;E-box binding