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
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 (642 variants)
Inborn_genetic_diseases (138 variants)
not_provided (101 variants)
not_specified (27 variants)
GAN-related_disorder (10 variants)
Charcot-Marie-Tooth_disease (5 variants)
Giant_axonal_neuropathy (2 variants)
Hypotonia (1 variants)
Peripheral_neuropathy (1 variants)
Intellectual_disability (1 variants)
See_cases (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. These statistics are base on transcript: NM_000022041.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	178 clinvar	1 clinvar	185
missense	6 clinvar	14 clinvar	344 clinvar	6 clinvar		370
nonsense	14 clinvar	6 clinvar	9 clinvar			29
start loss						0
frameshift	15 clinvar	5 clinvar	5 clinvar			25
splice donor/acceptor (+/-2bp)	2 clinvar	6 clinvar	5 clinvar			13
Total	37	31	369	184	1

Highest pathogenic variant AF is 0.000202029

Loading clinvar variants...

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
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
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