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

ENSG00000138185

∙ NCBI:953 ∙ OMIM:601752 ∙ HGNC:3363 ∙ Uniprot:P49961 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
hereditary spastic paraplegia 64 (Definitive), mode of inheritance: AR
neurodevelopmental disorder (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 64, autosomal recessive	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	Neurologic	24482476

ClinVar

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

Hereditary_spastic_paraplegia_64 (150 variants)
Inborn_genetic_diseases (49 variants)
not_provided (35 variants)
Hereditary_spastic_paraplegia (19 variants)
ENTPD1-related_disorder (5 variants)
Polymicrogyria (1 variants)
Global_developmental_delay (1 variants)
Microcephaly (1 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. These statistics are base on transcript: NM_000001776.6. 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			4 clinvar	46 clinvar	1 clinvar	51
missense	1 clinvar	1 clinvar	88 clinvar	7 clinvar	1 clinvar	98
nonsense	7 clinvar	1 clinvar	1 clinvar			9
start loss						0
frameshift	2 clinvar	2 clinvar				4
splice donor/acceptor (+/-2bp)		4 clinvar				4
Total	10	8	93	53	2

Highest pathogenic variant AF is 0.0000131375

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ENTPD1	protein_coding	protein_coding	ENST00000371207	10	165488

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00807	0.991	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.832	226	264	0.856	0.0000130	3467
Missense in Polyphen		68	98.714	0.68886		1301
Synonymous	1.09	89	103	0.863	0.00000573	967
Loss of Function	3.02	8	24.0	0.334	0.00000104	303

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

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

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

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