ATL3

atlastin GTPase 3, the group of Atlastins

Basic information

Region (hg38): 11:63624086-63671921

Links

ENSG00000184743 ∙ NCBI:25923 ∙ OMIM:609369 ∙ HGNC:24526 ∙ Uniprot:Q6DD88 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuropathy, hereditary sensory, type 1F (Moderate), mode of inheritance: AD
• neuropathy, hereditary sensory, type 1F (Strong), mode of inheritance: AD
• hereditary sensory and autonomic neuropathy type 1 (Supportive), mode of inheritance: AD
• neuropathy, hereditary sensory, type 1F (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory, type IF	AD	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	Neurologic	24459106; 30680846
Insensitivity to pain can result in injuries and infections

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATL3 gene.

• Neuropathy, hereditary sensory, type 1F (325 variants)
• Inborn genetic diseases (75 variants)
• not provided (56 variants)
• not specified (3 variants)
• Charcot-Marie-Tooth disease axonal type 2N (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATL3 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			2	72	5	79
missense			160	7	1	168
nonsense			6	1		7
start loss			1			1
frameshift			5			5
inframe indel			4			4
splice donor/acceptor (+/-2bp)			7			7
splice region			13	13	1	27
non coding			1	47	22	70
Total	0	0	186	127	28

Variants in ATL3

This is a list of pathogenic ClinVar variants found in the ATL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-63629309-C-T		ATL3-related disorder	Likely benign (Mar 18, 2019)
11-63629322-T-C		Neuropathy, hereditary sensory, type 1F	Likely benign (Mar 15, 2021)
11-63629325-A-T		Neuropathy, hereditary sensory, type 1F	Likely benign (Mar 23, 2023)
11-63629327-C-A		Inborn genetic diseases	Uncertain significance (Oct 30, 2020)
11-63629336-C-T		Neuropathy, hereditary sensory, type 1F • Inborn genetic diseases	Likely benign (Dec 19, 2023)
11-63629340-G-A		Neuropathy, hereditary sensory, type 1F	Likely benign (Oct 18, 2023)
11-63629343-T-C		Neuropathy, hereditary sensory, type 1F	Likely benign (Nov 11, 2020)
11-63629346-T-C		Neuropathy, hereditary sensory, type 1F	Benign (Jan 31, 2024)
11-63629347-C-T		Neuropathy, hereditary sensory, type 1F	Uncertain significance (Jun 27, 2022)
11-63629358-T-C		Neuropathy, hereditary sensory, type 1F	Likely benign (Dec 09, 2023)
11-63629362-T-TC		not specified	Uncertain significance (Jul 28, 2023)
11-63629372-T-C		Neuropathy, hereditary sensory, type 1F	Uncertain significance (Jul 26, 2023)
11-63629380-G-A		Neuropathy, hereditary sensory, type 1F	Uncertain significance (Mar 20, 2023)
11-63629389-C-T		Neuropathy, hereditary sensory, type 1F	Uncertain significance (Aug 23, 2022)
11-63629390-C-T		Inborn genetic diseases	Uncertain significance (Sep 17, 2019)
11-63629391-G-A		Neuropathy, hereditary sensory, type 1F	Likely benign (Oct 23, 2022)
11-63629393-T-C		Neuropathy, hereditary sensory, type 1F • Inborn genetic diseases	Likely benign (Dec 05, 2023)
11-63629395-T-C		Neuropathy, hereditary sensory, type 1F	Uncertain significance (Mar 13, 2019)
11-63629402-A-C		Neuropathy, hereditary sensory, type 1F	Uncertain significance (Mar 11, 2021)
11-63629417-C-A		Neuropathy, hereditary sensory, type 1F	Likely benign (Jan 05, 2024)
11-63629422-A-G		Neuropathy, hereditary sensory, type 1F	Benign (Dec 13, 2023)
11-63629423-T-C		Neuropathy, hereditary sensory, type 1F	Likely benign (Oct 11, 2023)
11-63630800-CA-C			Benign (Mar 08, 2021)
11-63630800-C-CA			Likely benign (Apr 13, 2021)
11-63630800-C-CAA			Likely benign (Apr 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATL3	protein_coding	protein_coding	ENST00000398868	13	47835

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.33e-9	0.941	124731	0	64	124795	0.000256

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	232	287	0.809	0.0000141	3547
Missense in Polyphen		106	129.51	0.8185		1611
Synonymous	-0.679	112	103	1.08	0.00000527	1004
Loss of Function	1.98	19	30.9	0.616	0.00000174	369

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000502	0.000498
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.000239	0.000238
Middle Eastern	0.0000556	0.0000556
South Asian	0.000789	0.000785
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase tethering membranes through formation of trans- homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis (PubMed:18270207, PubMed:19665976, PubMed:27619977). {ECO:0000269|PubMed:18270207, ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:27619977}.

Intolerance Scores

• loftool: 0.584
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.476
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.275

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atl3

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;endoplasmic reticulum organization;Golgi organization;protein homooligomerization;positive regulation of endoplasmic reticulum tubular network organization
• Cellular component: endoplasmic reticulum;membrane;integral component of membrane;endoplasmic reticulum tubular network;endoplasmic reticulum tubular network membrane
• Molecular function: GTPase activity;protein binding;GTP binding;identical protein binding