GeneBe

APTX

protein-coding

aprataxin, the group of Histidine triad superfamily

Gene summary

This gene encodes a member of the histidine triad (HIT) superfamily. The encoded protein may play a role in single-stranded DNA repair through its nucleotide-binding activity and its diadenosine polyphosphate hydrolase activity. Mutations in this gene have been associated with ataxia-ocular apraxia. Alternatively spliced transcript variants have been identified for this gene.[provided by RefSeq, Aug 2010]

Previous symbols:
  • AXA1

MANE transcript

NM_001195248.2

Inheritance

AR

ClinVar variants

P:43U:101B:52

Top phenotype

Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr9:32,886,601-33,025,130

External References & Databases

Ensembl (ENSG00000137074)NCBI Gene (54840)OMIM (606350)HGNC:15984GenCCUniProt (Q7Z2E3)AlphaFoldClinVar (APTX)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~138.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008842

Submitter: Labcorp Genetics (formerly Invitae)

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008842

Submitter: G2P

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008842

Submitter: Orphanet

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008842

Submitter: PanelApp Australia

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008842

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemiaAR

Manifestation: Gastrointestinal; Neurologic

Intervention: General

Rationale: 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

Refs: 3239952; 11586299; 11586300; 11294920; 12196655; 14506070; 12629250; 15365154; 15596775;15852392; 15699391; 17572444; 17242337; 18403580; 21465257; 21486904Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to APTX variants in ClinVar

8 Conditions Cataloged
not providedTotal: 211
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemiaTotal: 63
not specifiedTotal: 43
Inborn genetic diseasesTotal: 43
APTX-related disorderTotal: 11
EpilepsyTotal: 1
Coenzyme Q10 deficiency, primary, 1Total: 1
Hereditary ataxiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001195248.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
39
clinvar
3
clinvar
 47
missense
3
clinvar
6
clinvar
89
clinvar
10
clinvar
 108
nonsense
6
clinvar
5
clinvar
1
clinvar
 12
start loss
1
clinvar
 1
frameshift
9
clinvar
7
clinvar
1
clinvar
 17
splice donor/acceptor (+/-2bp)
3
clinvar
4
clinvar
4
clinvar
 11
Total2122101493196

Highest pathogenic variant AF is 0.000569575

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 161 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001195248.2RefSeqNP_001182177.27MANE Select
ENST00000379817.7EnsemblENSP00000369145.27MANE Select
NM_001195249.2RefSeqNP_001182178.17Standard
NM_001195250.2RefSeqNP_001182179.26Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • DNA-PK pathway in nonhomologous end joining

Biological Process

  • single strand break repair
  • DNA ligation
  • double-strand break repair
  • cellular response to DNA damage stimulus
  • dephosphorylation

Molecular Function

  • chromatin binding
  • damaged DNA binding
  • double-stranded DNA binding
  • single-stranded DNA binding
  • double-stranded RNA binding

Cellular Component

  • chromatin
  • nuclear chromatin
  • nucleus
  • nucleoplasm
  • nucleolus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000379813
Coding exons
7
Length
52563
Individuals with no LoFs
125672
Homozygous LoFs
0
Heterozygous LoFs
75
Defined
125747
p
0.000298
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3671971831.080.000009692253
Missense (PolyPhen)6568.6570.94674861
Synonymous0.1846465.90.9710.00000333640
Loss of Function0.5771618.70.8560.00000113197

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000380.00038rare
Ashkenazi Jewish0.000690.00069rare
East Asian0.0000540.000054rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000370.00037rare
South Asian0.000200.00020rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.293

Intolerance Scores

LoFtool
0.277
RVIS EVS
0.46
RVIS percentile EVS
78.59

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.970

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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