MAX

Chr 14

MYC associated transcriptional regulator X

Also known as: MEN5, PDMCS, bHLHd4

NCBI Gene: 4149 ENSG00000125952 UniProt: P61244

MAX encodes a basic helix-loop-helix leucine zipper transcription factor that forms heterodimers with MYC and MAD proteins to regulate gene expression by binding to E-box DNA sequences. Mutations cause autosomal dominant pheochromocytoma susceptibility and polydactyly-macrocephaly syndrome. The gene is highly constrained against loss-of-function variants (pLI 0.83, LOEUF 0.46), reflecting its essential role in transcriptional regulation.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. It is able to form homodimers and heterodimers with other family members, which include Mad, Mxi1 and Myc. Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E box) and rearrangement among these dimer forms provides a complex system of transcriptional regulation. Mutations of this gene have been reported to be associated with hereditary pheochromocytoma. A pseudogene of this gene is located on the long arm of chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPheochromocytoma

UniProtPolydactyly-macrocephaly syndrome

Clinical highlights

Gene-disease validity (ClinGen)

hereditary pheochromocytoma-paraganglioma · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

11069

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — MAX

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.834

Z-score 2.68

OE 0.10 (0.03–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.81Z-score

OE missense 0.48 (0.37–0.61)

45 obs / 94.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.03–0.46)

0≤0.351.4

Missense OE?0.48 (0.37–0.61)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 1 / 10.3Missense obs/exp: 45 / 94.6Syn Z: 0.56

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MAX · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — MAX

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

ANCA Associated Vasculitis (AAV)

The Safety, Efficacy, and Cellular Metabolic Kinetics of CT1192 in Treating Patients With Anti Neutrophil Cytoplasmic Antibody Associated Vasculitis

NOT YET RECRUITING

NCT07033299Phase PHASE1Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyStarted 2025-07-01

CAR-T Therapy

CMTCMT (Charcot Marie Tooth Disease)CMT - Charcot-Marie-Tooth Disease

A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)

RECRUITING

NCT07476365University Medical Center GoettingenStarted 2025-03-24

Friedreich's Ataxia

Biomarkers in Friedreich's Ataxia

RECRUITING

NCT02497534University of FloridaStarted 2015-09

Myotonic Dystrophy

A Study to Investigate the Safety, Tolerability, and Efficacy of SAR446268, an Adeno-associated Viral Vector-mediated Gene Therapy in Participants Aged 10 to 55 Years of Age With Non-congenital Myotonic Dystrophy Type 1

RECRUITING

NCT06844214Phase PHASE1, PHASE2SanofiStarted 2025-07-23

SAR446268

Treatment of Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)

A Clinical Trial of EHT102 Injection in Pediatric Patients With Biallelic hOTOF Mutations

RECRUITING

NCT07288580Phase PHASE1, PHASE2Shanghai Euhearing Therapeutics Co., LtdStarted 2026-04-02

EHT102 Injection

Fabry Disease

Natural History in Fabry Disease With IVS4+919G>A Mutations

ACTIVE NOT RECRUITING

NCT07506083Chinese University of Hong KongStarted 2022-10-20