MAX

Chr 14AD

MYC associated transcriptional regulator X

Also known as: PDMCS, bHLHd4

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.462 OMIM phenotypes
Clinical SummaryMAX
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Gene-Disease Validity (ClinGen)
hereditary pheochromocytoma-paraganglioma · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — MAX
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.834
Z-score 2.68
OE 0.10 (0.030.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.81Z-score
OE missense 0.48 (0.370.61)
45 obs / 94.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.030.46)
00.351.4
Missense OE0.48 (0.370.61)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 1 / 10.3Missense obs/exp: 45 / 94.6Syn Z: 0.56
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMAX-related pheochromocytoma, susceptibility toLOFAD
DN
0.4982th %ile
GOF
0.2895th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.46

Literature Evidence

LOFIndeed 14q deletion is a recurrent somatic rearrangement in NB and MAX somatic and germline loss of function mutation have recently been described in pheochromocytoma and paraganglioma.PMID:24665034

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Melanoma

Adoptive T Cell Immunotherapy for Advanced Melanoma Using Engineered Lymphocytes

RECRUITING
NCT02870244Phase PHASE1Loyola UniversityStarted 2015-02
Escalating Doses
Hematological Malignancies

Exploratory Study on in Vivo CAR-T Therapy Targeting CD20 for the Treatment of Hematological Malignancies

NOT YET RECRUITING
NCT07362602Phase EARLY_PHASE1The 923rd Hospital of Joint Logistics Support Force of People's Liberation ArmyStarted 2026-01-26
In vivo CAR-T drug targeting CD20 based on mRNA-LNP
Skin MicrobiomeGraft Versus Host DiseaseGraft Versus Host Disease in Skin

The Skin Microbiome in Graft Versus Host Disease

ACTIVE NOT RECRUITING
NCT04231500University Hospital, Basel, SwitzerlandStarted 2023-03-01
Skin swabsSkin punch biopsiesadditional blood sampling
MelanomaNon-Small-Cell Lung CancerThyroid Cancer

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.

RECRUITING
NCT05355701Phase PHASE1PfizerStarted 2022-07-05
PF-07799933binimetinibcetuximab
Muscular Atrophy, Spinal

A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy

RECRUITING
NCT05861986Phase PHASE4Hoffmann-La RocheStarted 2024-05-30
Risdiplam
Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING
NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01
ST-01156
Postnatal Depression

Home-based Transcranial Direct Current Stimulation in Postpartum Depression: the Feasibility Study and Pilot Study

NOT YET RECRUITING
NCT05046405Phase NAAna Ganho ÁvilaStarted 2022-10-02
Transcranial Direct Current Stimulation
Interstitial Lung DiseasePulmonary FibrosisInterstitial Lung Fibrosis

P4O2 ILD Extension

RECRUITING
NCT06644144Amsterdam UMC, location VUmcStarted 2024-11-01
No Interventions
Malignant Glioma of BrainAstrocytomaMalignant Astrocytoma

Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

RECRUITING
NCT05686798Phase PHASE1Henry Ford Health SystemStarted 2022-11-29
Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Head and Neck Carcinoma of Unknown PrimaryHead and Neck Squamous Cell CarcinomaStage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7

Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer

ACTIVE NOT RECRUITING
NCT02567422Phase PHASE1National Cancer Institute (NCI)Started 2017-04-17
BerzosertibCisplatinComputed Tomography
HSPHereditary Spastic ParaplegiaHereditary Spastic Paraparesis

Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)

NOT YET RECRUITING
NCT06948019Phase PHASE1, PHASE2BlackfinBio LtdStarted 2025-08
BFB-101 (AAV9-CBh-AP4B1)
Endocrine TumorsNon-Small Cell Lung CancerOvarian Cancer

Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer

RECRUITING
NCT03412877Phase PHASE2National Cancer Institute (NCI)Started 2018-09-06
CyclophosphamideFludarabineAldesleukin
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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