MAX
MYC associated factor X, the group of Basic helix-loop-helix proteins
Basic information
Region (hg38): 14:65006174-65102695
Links
Phenotypes
GenCC
Source:
- 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
- polydactyly-macrocephaly syndrome (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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 | Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal | 21685915; 38141607 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary_pheochromocytoma-paraganglioma (378 variants)
- Hereditary_cancer-predisposing_syndrome (279 variants)
- not_provided (62 variants)
- Pheochromocytoma (36 variants)
- not_specified (12 variants)
- MAX-related_disorder (10 variants)
- Polydactyly-macrocephaly_syndrome (6 variants)
- Pheochromocytoma,_susceptibility_to (5 variants)
- MAX-associated_Macrocephaly_and_Polydactyly_syndrome (1 variants)
- Retinoblastoma (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. These statistics are base on transcript: NM_000002382.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 117 | 121 | ||||
| missense | 213 | 224 | ||||
| nonsense | 10 | 15 | ||||
| start loss | 3 | 1 | 4 | |||
| frameshift | 15 | 26 | ||||
| splice donor/acceptor (+/-2bp) | 15 | |||||
| Total | 33 | 19 | 231 | 122 | 0 |
Highest pathogenic variant AF is 7.26116e-7
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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