GAN

gigaxonin, the group of Kelch like|BTB domain containing

Basic information

Region (hg38): 16:81314944-81390884

Links

ENSG00000261609 ∙ NCBI:8139 ∙ OMIM:605379 ∙ HGNC:4137 ∙ Uniprot:Q9H2C0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• giant axonal neuropathy 1 (Supportive), mode of inheritance: AR
• giant axonal neuropathy 1 (Strong), mode of inheritance: AR
• giant axonal neuropathy 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Giant axonal neuropathy 1, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Musculoskeletal; Neurologic	11062483; 11053687; 18595793; 19231187; 20301315; 20949505; 21356581

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GAN gene.

• Giant axonal neuropathy 1 (24 variants)
• Inborn genetic diseases (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GAN gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	145	2	152
missense	1	4	286	1		292
nonsense	14	2	2			18
start loss						0
frameshift	10	3	1			14
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	6	1			9
splice region			16	11	1	28
non coding			47	83	51	181
Total	27	15	344	229	53

Highest pathogenic variant AF is 0.00000658

Variants in GAN

This is a list of pathogenic ClinVar variants found in the GAN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-81314987-C-T		Giant axonal neuropathy 1	Uncertain significance (Jan 13, 2018)
16-81314988-T-C		Giant axonal neuropathy 1	Uncertain significance (Jan 13, 2018)
16-81315003-G-A		Giant axonal neuropathy 1	Uncertain significance (Jan 13, 2018)
16-81315039-G-C		Giant axonal neuropathy 1	Benign (Jun 20, 2018)
16-81315040-G-C		Giant axonal neuropathy 1	Uncertain significance (Jan 12, 2018)
16-81315044-C-T		Giant axonal neuropathy 1	Uncertain significance (Jan 12, 2018)
16-81315067-G-A		not specified	Likely benign (Jun 12, 2017)
16-81315099-G-C		Giant axonal neuropathy 1	Uncertain significance (Apr 27, 2017)
16-81315117-G-A		Giant axonal neuropathy 1	Uncertain significance (Sep 02, 2021)
16-81315119-T-G		Giant axonal neuropathy 1	Likely benign (Nov 06, 2023)
16-81315122-G-A		Giant axonal neuropathy 1	Likely benign (Apr 04, 2022)
16-81315123-G-A		Giant axonal neuropathy 1	Uncertain significance (Feb 25, 2021)
16-81315126-A-C			Uncertain significance (Feb 01, 2022)
16-81315127-G-A		Giant axonal neuropathy 1	Uncertain significance (Jul 26, 2020)
16-81315127-G-C		Giant axonal neuropathy 1	Uncertain significance (Oct 08, 2020)
16-81315130-C-T		Giant axonal neuropathy 1	Uncertain significance (Feb 03, 2022)
16-81315130-CCGTGTCTGACCCTCAGCACGCCGCGCGTCTGCTGCGAG-C		Giant axonal neuropathy 1	Uncertain significance (Jan 06, 2016)
16-81315131-C-T		Giant axonal neuropathy 1	Likely benign (Feb 21, 2023)
16-81315131-C-CA		Giant axonal neuropathy 1	Conflicting classifications of pathogenicity (Jan 06, 2016)
16-81315136-C-G		Charcot-Marie-Tooth disease • Giant axonal neuropathy 1	Uncertain significance (May 01, 2022)
16-81315138-G-T		Giant axonal neuropathy 1	Uncertain significance (Dec 02, 2021)
16-81315140-C-G		Giant axonal neuropathy 1	Uncertain significance (Jun 14, 2023)
16-81315140-C-T		Giant axonal neuropathy 1	Likely benign (Jul 13, 2023)
16-81315141-C-T		Giant axonal neuropathy 1	Uncertain significance (Jun 30, 2023)
16-81315142-C-G		Giant axonal neuropathy 1	Uncertain significance (Jul 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GAN	protein_coding	protein_coding	ENST00000568107	11	75933

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0248	0.975	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.726	367	330	1.11	0.0000201	3909
Missense in Polyphen		64	76.897	0.83228		908
Synonymous	-4.75	189	122	1.55	0.00000812	1130
Loss of Function	3.71	9	31.4	0.286	0.00000181	369

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000468	0.000468
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000132	0.000123
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000269|PubMed:12147674, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16227972, ECO:0000269|PubMed:16303566}.
• Disease: DISEASE: Giant axonal neuropathy 1, autosomal recessive (GAN1) [MIM:256850]: A severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. Axonal loss and the presence of giant axonal swellings filled with neurofilaments on nerve biopsies are the hallmarks of this neurodegenerative disorder. {ECO:0000269|PubMed:11062483, ECO:0000269|PubMed:11971098, ECO:0000269|PubMed:12655563, ECO:0000269|PubMed:16303566, ECO:0000269|PubMed:17578852, ECO:0000269|PubMed:17587580}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation (Consensus)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.353
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.14

Haploinsufficiency Scores

• pHI: 0.246
• hipred: N
• hipred_score: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.720

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gan
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; cellular phenotype

Gene ontology

• Biological process: cytoskeleton organization;protein ubiquitination;post-translational protein modification
• Cellular component: cytoplasm;cytosol;cytoskeleton;Cul3-RING ubiquitin ligase complex
• Molecular function: molecular_function;protein binding