APTX

aprataxin, the group of Histidine triad superfamily

Basic information

Region (hg38): 9:32886601-33025130

Previous symbols: [ "AXA1" ]

Links

ENSG00000137074

∙ NCBI:54840 ∙ OMIM:606350 ∙ HGNC:15984 ∙ Uniprot:Q7Z2E3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (Definitive), mode of inheritance: AR
ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (Strong), mode of inheritance: AR
ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (Strong), mode of inheritance: AR
ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	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	Gastrointestinal; Neurologic	3239952; 11586299; 11586300; 11294920; 12196655; 14506070; 12629250; 15365154; 15596775;15852392; 15699391; 17572444; 17242337; 18403580; 21465257; 21486904

ClinVar

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

not_provided (194 variants)
Ataxia,_early-onset,_with_oculomotor_apraxia_and_hypoalbuminemia (58 variants)
Inborn_genetic_diseases (39 variants)
not_specified (33 variants)
Spinocerebellar_ataxia,_autosomal_recessive,_with_axonal_neuropathy_2 (6 variants)
APTX-related_disorder (6 variants)
Coenzyme_Q10_deficiency,_Oculomotor_Apraxia_Type (4 variants)
Epilepsy (1 variants)
Coenzyme_Q10_deficiency,_primary,_1 (1 variants)
Hereditary_ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APTX gene is commonly pathogenic or not. These statistics are base on transcript: NM_001195248.2. 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			5 clinvar	34 clinvar	3 clinvar	42
missense	4 clinvar	5 clinvar	81 clinvar	10 clinvar		100
nonsense	6 clinvar	4 clinvar				10
start loss			1			1
frameshift	11 clinvar	5 clinvar				16
splice donor/acceptor (+/-2bp)	3 clinvar	4 clinvar	2 clinvar			9
Total	24	18	89	44	3

Highest pathogenic variant AF is 0.000569575

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APTX	protein_coding	protein_coding	ENST00000379813	7	52563

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.99e-10	0.189	125672	0	75	125747	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.367	197	183	1.08	0.00000969	2253
Missense in Polyphen		65	68.657	0.94674		861
Synonymous	0.184	64	65.9	0.971	0.00000333	640
Loss of Function	0.577	16	18.7	0.856	0.00000113	197

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000622	0.000622
Ashkenazi Jewish	0.000694	0.000695
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000370	0.000369
Middle Eastern	0.0000544	0.0000544
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair (PubMed:15380105, PubMed:15044383, PubMed:16964241, PubMed:17276982, PubMed:24362567). Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species (PubMed:16964241, PubMed:24362567). Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined (PubMed:16964241, PubMed:17276982, PubMed:24362567). Also able to hydrolyze adenosine 5'- monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity (PubMed:16547001). Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA) (By similarity). {ECO:0000250|UniProtKB:O74859, ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16547001, ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, ECO:0000269|PubMed:24362567}.;
Disease: DISEASE: Ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]: An autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy. {ECO:0000269|PubMed:11586299, ECO:0000269|PubMed:11586300, ECO:0000269|PubMed:12196655, ECO:0000269|PubMed:12629250, ECO:0000269|PubMed:14506070, ECO:0000269|PubMed:15699391, ECO:0000269|PubMed:15852392, ECO:0000269|PubMed:24362567}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: DNA-PK pathway in nonhomologous end joining (Consensus)

Recessive Scores

pRec: 0.293

Intolerance Scores

loftool: 0.277
rvis_EVS: 0.46
rvis_percentile_EVS: 78.59

Haploinsufficiency Scores

pHI: 0.0721
hipred: Y
hipred_score: 0.572
ghis: 0.493

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Aptx
Phenotype: homeostasis/metabolism phenotype; cellular phenotype;

Gene ontology

Biological process: single strand break repair;DNA ligation;double-strand break repair;cellular response to DNA damage stimulus;dephosphorylation;regulation of protein stability;response to hydrogen peroxide;nucleic acid phosphodiester bond hydrolysis
Cellular component: chromatin;nuclear chromatin;nucleus;nucleoplasm;nucleolus;cytoplasm
Molecular function: chromatin binding;damaged DNA binding;double-stranded DNA binding;single-stranded DNA binding;double-stranded RNA binding;protein binding;phosphoglycolate phosphatase activity;mismatched DNA binding;DNA 5'-adenosine monophosphate hydrolase activity;metal ion binding;protein N-terminus binding;phosphoprotein binding;DNA-3'-diphospho-5'-guanosine diphosphatase;single-strand break-containing DNA binding