ATL1

atlastin GTPase 1, the group of Atlastins

Basic information

Region (hg38): 14:50532509-50634017

Previous symbols: [ "SPG3", "SPG3A" ]

Links

ENSG00000198513 ∙ NCBI:51062 ∙ OMIM:606439 ∙ HGNC:11231 ∙ Uniprot:Q8WXF7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 3A (Definitive), mode of inheritance: Semidominant
• neuropathy, hereditary sensory, type 1D (Moderate), mode of inheritance: AD
• hereditary sensory and autonomic neuropathy type 1 (Supportive), mode of inheritance: AD
• hereditary spastic paraplegia 3A (Supportive), mode of inheritance: AD
• neuropathy, hereditary sensory, type 1D (Strong), mode of inheritance: AD
• hereditary spastic paraplegia 3A (Strong), mode of inheritance: AD
• neuropathy, hereditary sensory, type 1D (Definitive), mode of inheritance: AD
• hereditary spastic paraplegia 3A (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory, type 1D; Spastic paraplegia 3, autosomal dominant	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	11685207; 12112092; 15517445; 15596607; 16401858; 16533974; 17502470; 21194679; 21336785; 24473461
Congenital insensitivity to pain can result in injuries and infections

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATL1 gene.

• Hereditary_spastic_paraplegia_3A (464 variants)
• not_provided (155 variants)
• Inborn_genetic_diseases (81 variants)
• Neuropathy,_hereditary_sensory,_type_1D (32 variants)
• not_specified (24 variants)
• Hereditary_spastic_paraplegia (18 variants)
• ATL1-related_disorder (8 variants)
• Spastic_paraplegia (2 variants)
• Neurodevelopmental_delay (2 variants)
• Charcot-Marie-Tooth_disease (2 variants)
• Spastic_paraplegia,_autosomal_dominant (1 variants)
• Osteomyelitis_leading_to_amputation_due_to_slow_healing_fractures (1 variants)
• Abnormal_pyramidal_sign (1 variants)
• ATL1-related_spastic_paraplegia,_recessive (1 variants)
• See_cases (1 variants)
• Distal_lower_limb_muscle_weakness (1 variants)
• Distal_sensory_impairment (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Penetrating_foot_ulcers (1 variants)
• Lingual_thyroid (1 variants)
• Accessory_ectopic_thyroid_tissue (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATL1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015915.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	2	88	5	96
missense	25	59	235	9		328
nonsense	8	2	3			13
start loss						0
frameshift	4	6	5			15
splice donor/acceptor (+/-2bp)	1	3	1	1		6
Total	38	71	246	98	5

Highest pathogenic variant AF is 0.00001797

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATL1	protein_coding	protein_coding	ENST00000358385	14	100560

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0189	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.63	168	295	0.569	0.0000147	3672
Missense in Polyphen		24	69.335	0.34614		906
Synonymous	0.0805	106	107	0.990	0.00000538	1023
Loss of Function	4.62	5	34.2	0.146	0.00000177	403

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

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:27619977). May also regulate Golgi biogenesis. May regulate axonal development. {ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:17321752, ECO:0000269|PubMed:18270207, ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:21220294, ECO:0000269|PubMed:23334294, ECO:0000269|PubMed:25751282, ECO:0000269|PubMed:27619977}.
• Disease: DISEASE: Neuropathy, hereditary sensory, 1D (HSN1D) [MIM:613708]: A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement. {ECO:0000269|PubMed:21194679}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.198
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.44

Haploinsufficiency Scores

• pHI: 0.581
• hipred: Y
• hipred_score: 0.673
• ghis: 0.629

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.453

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atl1
• Phenotype: limbs/digits/tail phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: atl1
• Affected structure: secondary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: endoplasmic reticulum organization;axonogenesis;protein homooligomerization;endoplasmic reticulum tubular network membrane organization
• Cellular component: Golgi cis cisterna;Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;integral component of membrane;axon;endoplasmic reticulum tubular network;endoplasmic reticulum tubular network membrane
• Molecular function: GTPase activity;protein binding;GTP binding;identical protein binding