GAN

Chr 16AR

gigaxonin

Also known as: GAN1, GIG, KLHL16

NCBI Gene: 8139 ENSG00000261609 UniProt: Q9H2C0 OMIM: 605379

The protein functions as a cytoskeletal component that maintains neurofilament architecture and acts as a substrate-specific adapter for ubiquitin-mediated degradation of neuronal proteins including MAP1B and TBCB. Mutations cause giant axonal neuropathy-1, a progressive neurodegenerative disorder that typically presents in early childhood with peripheral neuropathy and distinctive giant axons containing neurofilament accumulations. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the cytoskeletal BTB/kelch (Broad-Complex, Tramtrack and Bric a brac) repeat family. The encoded protein plays a role in neurofilament architecture and is involved in mediating the ubiquitination and degradation of some proteins. Defects in this gene are a cause of giant axonal neuropathy (GAN). [provided by RefSeq, Oct 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Giant axonal neuropathy-1MIM #256850

Clinical highlights

Management implications

GAN has therapies in development

Gene-disease validity (ClinGen)

giant axonal neuropathy 1 · ARDefinitivesufficient 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

2003

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

LOF

Mechanism· G2P

scAAV9/JeT-GAN
AAV gene therapyPhase 1
Intrathecal delivery of the GAN gene.
Delivery: Intrathecal

Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.

ClinicalTrials.gov

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.025

Z-score 3.71

OE 0.29 (0.17–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.73Z-score

OE missense 1.11 (1.02–1.21)

367 obs / 329.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.29 (0.17–0.50)

0≤0.351.4

Missense OE?1.11 (1.02–1.21)

0≤0.61.4

Synonymous OE?1.55

0≤1.21.6

LoF obs/exp: 9 / 31.4Missense obs/exp: 367 / 329.9Syn Z: -4.74

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GAN · 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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Seasonal Allergic RhinitisSAR

A Phase III Study to Assess the Efficacy and Safety of PG-011 Nasal Spray in Adults With Moderate to Severe Seasonal Allergic Rhinitis

NOT YET RECRUITING

NCT07146126Phase PHASE3Prime Gene Therapeutics Co., Ltd.Started 2025-09-15

PG-011 nasal spray 0.6%(twice daily)Placebo

Acute Myeloid LeukemiaAcute Lymphoblastic LeukemiaMixed Lineage Acute Leukemia

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

RECRUITING

NCT04065399Phase PHASE1, PHASE2Syndax PharmaceuticalsStarted 2019-11-05

revumenibcobicistat

Mitochondrial DiseasesPearson Syndrome

Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)

RECRUITING

NCT06017869Phase PHASE2Minovia Therapeutics Ltd.Started 2023-07-31

MNV-201

Non-Allergic Rhinitis With Eosinophilia Syndrome

Efficacy and Safety of Stapokibart in Non-Allergic Rhinitis With Eosinophilia Syndrome

NOT YET RECRUITING

NCT07240376Phase NAHuazhong University of Science and TechnologyStarted 2025-11-25

Stapokibart (CM310)Placebo

Neovascular Age-Related Macular Degeneration (nAMD)

Single Intravitreal (IVT) Injection of 4D-150 in Patients With Macular Neovascularization Secondary to Age-Related Macular Degeneration

RECRUITING

NCT07064759Phase PHASE34D Molecular TherapeuticsStarted 2025-07-22