ENTPD1

ectonucleoside triphosphate diphosphohydrolase 1, the group of CD molecules|Ectonucleoside triphosphate diphosphohydrolase family

Basic information

Region (hg38): 10:95711779-95877266

Previous symbols: [ "CD39" ]

Links

ENSG00000138185NCBI:953OMIM:601752HGNC:3363Uniprot:P49961AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • hereditary spastic paraplegia 64 (Moderate), mode of inheritance: AR
  • hereditary spastic paraplegia 64 (Strong), mode of inheritance: AR
  • hereditary spastic paraplegia 64 (Limited), mode of inheritance: AR
  • hereditary spastic paraplegia 64 (Supportive), mode of inheritance: AR
  • hereditary spastic paraplegia 64 (Limited), mode of inheritance: AR
  • complex hereditary spastic paraplegia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Spastic paraplegia 64, autosomal recessiveARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic24482476

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ENTPD1 gene.

  • Hereditary spastic paraplegia 64 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ENTPD1 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
4
clinvar
35
clinvar
2
clinvar
41
missense
72
clinvar
1
clinvar
73
nonsense
2
clinvar
2
clinvar
4
start loss
0
frameshift
1
clinvar
1
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
0
splice region
1
3
6
10
non coding
5
clinvar
23
clinvar
21
clinvar
49
Total 3 0 84 58 24

Variants in ENTPD1

This is a list of pathogenic ClinVar variants found in the ENTPD1 region.

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

Position Type Phenotype Significance ClinVar
10-95711826-T-C Likely benign (Apr 09, 2021)1300977
10-95711989-G-A Conflicting classifications of pathogenicity (Aug 01, 2024)2498467
10-95712168-T-C Benign (Nov 11, 2018)1292728
10-95727661-T-G Uncertain significance (Jul 05, 2023)2576127
10-95755380-G-A Hereditary spastic paraplegia 64 Benign (Nov 29, 2022)1249702
10-95755766-G-A Hereditary spastic paraplegia 64 Conflicting classifications of pathogenicity (Jul 01, 2024)547899
10-95755831-T-C Benign (Apr 08, 2021)1234750
10-95756154-A-C Hereditary spastic paraplegia Uncertain significance (Dec 22, 2016)1344321
10-95756268-T-C Hereditary spastic paraplegia 64 Likely benign (Dec 03, 2021)1620047
10-95756521-GT-G Benign (Apr 16, 2021)1274919
10-95823211-T-C Likely benign (May 11, 2021)1342044
10-95823221-C-T Hereditary spastic paraplegia 64 Likely benign (Jan 08, 2024)2980704
10-95823224-C-T Hereditary spastic paraplegia 64 Likely benign (Jul 12, 2023)2980534
10-95823239-T-G Hereditary spastic paraplegia 64 • Inborn genetic diseases Uncertain significance (May 24, 2023)1899010
10-95823244-C-T Hereditary spastic paraplegia 64 • ENTPD1-related disorder Likely benign (Feb 01, 2023)1654089
10-95823245-G-A Global developmental delay;Microcephaly;Polymicrogyria • Hereditary spastic paraplegia 64 • Hereditary spastic paraplegia Uncertain significance (Sep 12, 2022)374088
10-95823249-A-C Inborn genetic diseases Uncertain significance (Aug 08, 2022)2305548
10-95823259-C-T Hereditary spastic paraplegia 64 Likely benign (Jan 22, 2024)1351116
10-95823263-A-G Hereditary spastic paraplegia 64 Uncertain significance (Sep 19, 2023)2849350
10-95823284-G-T Inborn genetic diseases Uncertain significance (Jan 07, 2022)2271031
10-95823298-C-G Hereditary spastic paraplegia 64 Uncertain significance (Sep 10, 2021)1365381
10-95823354-A-C Inborn genetic diseases Uncertain significance (Mar 20, 2023)2526907
10-95823358-C-T Hereditary spastic paraplegia 64 Likely benign (Oct 31, 2022)2990811
10-95823359-G-A Hereditary spastic paraplegia Uncertain significance (Jun 01, 2019)1344315
10-95823374-A-G Hereditary spastic paraplegia 64 Uncertain significance (May 26, 2020)1040596

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ENTPD1protein_codingprotein_codingENST00000371207 10165488
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.008070.9911257380101257480.0000398
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8322262640.8560.00001303467
Missense in Polyphen6898.7140.688861301
Synonymous1.09891030.8630.00000573967
Loss of Function3.02824.00.3340.00000104303

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001200.000120
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00004400.0000439
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Could also be implicated in the prevention of platelet aggregation by hydrolyzing platelet-activating ADP to AMP. Hydrolyzes ATP and ADP equally well. {ECO:0000269|PubMed:8955160}.;
Disease
DISEASE: Spastic paraplegia 64, autosomal recessive (SPG64) [MIM:615683]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:24482476}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Pyrimidine metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pyrimidine metabolism;Nucleobase catabolism;Metabolism of nucleotides;UTP and CTP dephosphorylation II;Phosphate bond hydrolysis by NTPDase proteins;Purine metabolism;Metabolism;Pyrimidine metabolism;Purine nucleotides nucleosides metabolism;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

pRec
0.239

Intolerance Scores

loftool
0.568
rvis_EVS
-0.34
rvis_percentile_EVS
30.56

Haploinsufficiency Scores

pHI
0.174
hipred
N
hipred_score
0.334
ghis
0.598

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.189

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Entpd1
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; muscle phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
cell adhesion;blood coagulation;nucleobase-containing small molecule catabolic process
Cellular component
plasma membrane;integral component of plasma membrane;membrane;extracellular exosome
Molecular function
protein binding;ATP binding;nucleoside-diphosphatase activity;nucleoside-triphosphatase activity;dATP phosphohydrolase activity;dCTP phosphohydrolase activity;dUTP phosphohydrolase activity;dTTP phosphohydrolase activity;GTP phosphohydrolase activity;8-oxo-dGTP phosphohydrolase activity;dGTP phosphohydrolase activity