GAN

Chr 16AR

gigaxonin

NCBI Gene: 8139ENSG00000261609UniProt: Q9H2C0

Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. May act as a substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB. Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival

Primary Disease Associations & Inheritance

Giant axonal neuropathy-1MIM #256850
AR
593
ClinVar variants
55
Pathogenic / LP
0.02
pLI score
12
Active trials
Clinical Summary— GAN
🧬
Gene-Disease Validity (ClinGen)
giant axonal neuropathy 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 307 VUS of 593 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.73Z-score
OE missense 1.11 (1.02–1.21)
367 obs / 329.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.17–0.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.02–1.21)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.55
0≤1.21.6
LoF obs/exp: 9 / 31.4Missense obs/exp: 367 / 329.9Syn Z: -4.74

ClinVar Variant Classifications

593 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic20
VUS307
Likely Benign199
Benign24
Conflicting8
35
Pathogenic
20
Likely Pathogenic
307
VUS
199
Likely Benign
24
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
23
0
35
Likely Pathogenic
7
3
10
0
20
VUS
4
252
46
5
307
Likely Benign
0
0
70
129
199
Benign
0
0
23
1
24
Conflicting
—8
Total21257172135593

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

Gene2Phenotype Curations

GAN-related giant axonal neuropathy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
GIGAXONIN; GAN
MIM #605379 · *

Giant axonal neuropathy-1

MIM #256850

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hepatoprotective effects of semaglutide, lanifibranor and dietary intervention in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH.
Møllerhøj MB et al.·Clin Transl Sci
2022Functional
Human translatability of the GAN diet-induced obese mouse model of non-alcoholic steatohepatitis.
Hansen HH et al.·BMC Gastroenterol
2020Functional
Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis.
Hansen HH et al.·Sci Rep
2023Functional
Intrathecal Gene Therapy for Giant Axonal Neuropathy.
Bharucha-Goebel DX et al.·N Engl J Med
2024
Giant axonal neuropathy.
Hentati F et al.·Handb Clin Neurol
2013Review
Generative Adversarial Networks in Cardiology.
Skandarani Y et al.·Can J Cardiol
2022Review
Tao J et al.·Yao Xue Xue Bao
2017
Advanced Studies on Rhizoma Dioscoreae Collettii.
Li LL et al.·Chin J Integr Med
2020Review
Clinical-GAN: Trajectory Forecasting of Clinical Events using Transformer and Generative Adversarial Networks.
Shankar V et al.·Artif Intell Med
2023
Applications of generative adversarial networks in neuroimaging and clinical neuroscience.
Wang R et al.·Neuroimage
2023Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
ObesityGenetic Obesity

EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

ACTIVE NOT RECRUITING
NCT05093634Phase PHASE3Rhythm Pharmaceuticals, Inc.Started 2021-12-10
SetmelanotidePlacebo
Solid Tumor

A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients

RECRUITING
NCT06010342Phase PHASE2Teligene USStarted 2023-03-16
TL118 Capsule
Pancreas CancerPancreas CystPancreatic Ductal Adenocarcinoma

Pancreatic Cancer Early Detection Consortium

RECRUITING
NCT04970056Arbor Research Collaborative for HealthStarted 2020-09-18
Neurofibromatosis Type 1

PASS of Paediatric Patients Initiating Selumetinib

RECRUITING
NCT05388370AstraZenecaStarted 2022-05-23
TNBC, Triple Negative Breast Cancer

Neoadjuvant Chemotherapy Combined With Toripalimab for TNBC (NEOTORCH-BREAST02)

RECRUITING
NCT06682195Phase PHASE2First Affiliated Hospital of Zhejiang UniversityStarted 2024-10-09
Neoadjuvant chemotherapy combined with Toripalimab
Leukemia, Myeloid, Acute

A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

RECRUITING
NCT06852222Phase PHASE3Janssen Research & Development, LLCStarted 2025-06-04
BleximenibVenetoclax (VEN)Azacitidine (AZA)
Acute Coronary Syndrome

A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome

ACTIVE NOT RECRUITING
NCT05754957Phase PHASE3Janssen Research & Development, LLCStarted 2023-04-07
MilvexianPlacebo
Hearing LossGenetic DiseaseSpeech Perception

A Comparative Analysis of Speech Perception Between Cochlear Implant Patients and DFNB9 Patients Receiving Gene Therapy

RECRUITING
NCT06237790Eye & ENT Hospital of Fudan UniversityStarted 2024-04-06
Carcinoma, Non-Small-Cell Lung

A Study of Clinical Outcomes in Participants With EGFR Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) in a Real-World Setting

RECRUITING
NCT07230691Janssen Research & Development, LLCStarted 2025-12-03
Prostate Cancer

A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation

RECRUITING
NCT06952803Phase PHASE3AstraZenecaStarted 2025-08-06
SaruparibPlaceboAbiraterone + Prednisolone/Prednisone
Non-small Cell Lung Cancer

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment

RECRUITING
NCT07195695Phase PHASE3Boehringer IngelheimStarted 2026-01-16
ZongertinibPembrolizumabAtezolizumab
Dry Eye

Preliminary Clinical Study of the Effectiveness and Safety of Ocular Surface Microbiota Transplantation in the Treatment of Dry Eye Disease

RECRUITING
NCT07298811Phase PHASE1, PHASE2Second Affiliated Hospital of Nanchang UniversityStarted 2025-10-01
Ocular surface microbiota transplantationPlacebo Group

External Resources

Links to major genomics databases and tools