APTX

aprataxin, the group of Histidine triad superfamily

Basic information

Region (hg38): 9:32886600-33025130

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 (198 variants)
• Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (69 variants)
• not specified (35 variants)
• Inborn genetic diseases (19 variants)
• Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (15 variants)
• Coenzyme Q10 deficiency, Oculomotor Apraxia Type (14 variants)
• Epilepsy (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.

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	27	2	31
missense	1	3	58	5		67
nonsense	4	4				8
start loss			1			1
frameshift	8	4				12
inframe indel						0
splice donor/acceptor (+/-2bp)	2		1			3
splice region			4	12	5	21
non coding	1		15	51	27	94
Total	16	11	77	83	29

Highest pathogenic variant AF is 0.000395

Variants in APTX

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

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

Position	Type	Phenotype	Significance	ClinVar
9-32972640-G-C		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Uncertain significance (Jan 13, 2018)
9-32972645-AAG-A		Coenzyme Q10 deficiency, Oculomotor Apraxia Type • Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Likely benign (Jun 14, 2016)
9-32972664-G-C		Coenzyme Q10 deficiency, Oculomotor Apraxia Type • Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Uncertain significance (Jun 14, 2016)
9-32972692-C-T		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Conflicting classifications of pathogenicity (May 10, 2021)
9-32972742-C-T		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Benign/Likely benign (Apr 09, 2022)
9-32972862-G-A		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Uncertain significance (Jan 13, 2018)
9-32972888-C-G		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Uncertain significance (Apr 27, 2017)
9-32972892-C-T		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • Coenzyme Q10 deficiency, Oculomotor Apraxia Type	Conflicting classifications of pathogenicity (May 10, 2021)
9-32972893-C-T		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Uncertain significance (Jan 13, 2018)
9-32973022-G-A		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Uncertain significance (Jan 13, 2018)
9-32973044-C-G		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • Coenzyme Q10 deficiency, Oculomotor Apraxia Type	Benign/Likely benign (Jan 13, 2018)
9-32973135-G-A		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • Coenzyme Q10 deficiency, Oculomotor Apraxia Type	Uncertain significance (Jan 13, 2018)
9-32973188-C-T		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Uncertain significance (Jan 13, 2018)
9-32973205-G-C		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Likely benign (Jan 13, 2018)
9-32973283-C-G		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Uncertain significance (Jan 13, 2018)
9-32973311-C-G		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • Coenzyme Q10 deficiency, Oculomotor Apraxia Type	Conflicting classifications of pathogenicity (Jun 01, 2019)
9-32973357-C-T		Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Benign/Likely benign (Dec 24, 2018)
9-32973519-G-A			Likely benign (Nov 27, 2023)
9-32973524-G-A			Uncertain significance (Dec 07, 2022)
9-32973538-G-T			Uncertain significance (Aug 26, 2016)
9-32973556-T-A		not specified • Coenzyme Q10 deficiency, Oculomotor Apraxia Type • Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia • APTX-related disorder	Conflicting classifications of pathogenicity (Jan 11, 2024)
9-32973567-A-G			Likely benign (Apr 04, 2022)
9-32973568-T-A		Inborn genetic diseases	Uncertain significance (Oct 13, 2022)
9-32973570-ACAACGAAGGGGCAGCTT-A			Pathogenic (Nov 01, 2018)
9-32973574-C-T			Uncertain significance (Feb 17, 2022)

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