GAN

Chr 16AR

gigaxonin

Also known as: GAN1, GIG, KLHL16

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]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.501 OMIM phenotype
Clinical SummaryGAN
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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.
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ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 448 VUS of 893 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.50LOEUF
pLI 0.025
Z-score 3.71
OE 0.29 (0.170.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-0.73Z-score
OE missense 1.11 (1.021.21)
367 obs / 329.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.29 (0.170.50)
00.351.4
Missense OE?1.11 (1.021.21)
00.61.4
Synonymous OE?1.55
01.21.6
LoF obs/exp: 9 / 31.4Missense obs/exp: 367 / 329.9Syn Z: -4.74
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGAN-related giant axonal neuropathyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6745th %ile
GOF
0.6834th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

893 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic24
VUS448
Likely Benign285
Benign59
Conflicting32
39
Pathogenic
24
Likely Pathogenic
448
VUS
285
Likely Benign
59
Benign
32
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
3
3
0
39
Likely Pathogenic
15
7
2
0
24
VUS
19
361
62
6
448
Likely Benign
0
1
108
176
285
Benign
0
0
57
2
59
Conflicting
32
Total67372232184887

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

View in ClinVar →

42 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap GAN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

GAN · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Pancreas CancerPancreas CystPancreatic Ductal Adenocarcinoma

Pancreatic Cancer Early Detection Consortium

RECRUITING
NCT04970056Arbor Research Collaborative for HealthStarted 2020-09-18
Diabetes Mellitus, Type 1

Multicenter Study of Fulminant Type 1 Diabetes in China

RECRUITING
NCT05593081Second Xiangya Hospital of Central South UniversityStarted 2022-05-20
HLA
Intrahepatic Cholangiocarcinoma (Icc)Advanced Cholangiocarcinoma

Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations

NOT YET RECRUITING
NCT07328919Phase PHASE3TransThera Sciences (Nanjing), Inc.Started 2026-01
TT-00420 (tinengotinib)Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine
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)
AADC Deficiency

A Study of SmartFlow Magnetic Resonance (MR) Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Participants

ACTIVE NOT RECRUITING
NCT04903288Phase PHASE2PTC TherapeuticsStarted 2021-05-12
Eladocagene Exuparvovec
Advanced Breast Cancer

Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer

RECRUITING
NCT06380751Phase PHASE3AstraZenecaStarted 2024-08-01
Saruparib (AZD5305)CamizestrantAbemaciclib
COPD

Respiratory Muscles in End-stage Lung Disease: Pathophysiological Processes & Clinical Consequences

NOT YET RECRUITING
NCT06935825University Medical Center GroningenStarted 2025-09-01
Mild Cognitive Impairment(MCI)Alzheimer Disease, Late OnsetFamilial Alzheimer Disease (FAD)

China Cognition and Aging Study

RECRUITING
NCT03653156Capital Medical UniversityStarted 2000-01-01
Giant Axonal Neuropathy (GAN)

Intraneural Administration of scAAV9/JeT-GAN Into the Vagus Nerve for Patients With Giant Axonal Neuropathy (GAN)

RECRUITING
NCT07543991Phase PHASE1University of Texas Southwestern Medical CenterStarted 2026-03-01
scAAV9/JeT-GAN
Advanced Solid Neoplasms

Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)

ACTIVE NOT RECRUITING
NCT03742895Phase PHASE2Merck Sharp & Dohme LLCStarted 2018-12-12
Olaparib
Metastatic Non-small Cell Lung Cancer

A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

RECRUITING
NCT06417814Phase PHASE3AstraZenecaStarted 2024-10-04
Dato-DXdOsimertinibPemetrexed
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