ENTPD6

protein-coding

ectonucleoside triphosphate diphosphohydrolase 6, the group of Ectonucleoside triphosphate diphosphohydrolase family

Gene summary

ENTPD6 is similar to E-type nucleotidases (NTPases). NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD6 contains 4 apyrase-conserved regions which are characteristic of NTPases. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

Previous symbols:

CD39L2
IL6ST2

MANE transcript

NM_001247.5

Inheritance

—

ClinVar variants

U:73B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr20:25,195,693-25,228,075

External References & Databases

Ensembl (ENSG00000197586)

Transcript & Mutation Effects

hg38 • Region Span ~32.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ENTPD6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001247.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	1 clinvar	1 clinvar	5
missense			68 clinvar	9 clinvar		77
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	73	10	1	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 150 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001247.5	RefSeq	NP_001238.3	14	MANE Select
ENST00000376652.9	Ensembl	ENSP00000365840.4	14	MANE Select
NM_001114089.4	RefSeq	NP_001107561.2	14	Standard
NM_001317941.3	RefSeq	NP_001304870.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Nucleobase catabolism
Metabolism of nucleotides
Phosphate bond hydrolysis by NTPDase proteins

Biological Process

response to magnesium ion
nucleobase-containing small molecule catabolic process
response to calcium ion

Molecular Function

guanosine-5'-triphosphate,3'-diphosphate diphosphatase activity
nucleoside-diphosphatase activity
nucleoside-triphosphatase activity
uridine-diphosphatase activity

Cellular Component

Golgi membrane
extracellular region
extracellular space
Golgi apparatus
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376652
Coding exons: 14
Length: 31037
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.766	261	298	0.875	0.0000185	3110
Missense (PolyPhen)		85	109.86	0.77373		1202
Synonymous	0.747	118	129	0.916	0.00000901	976
Loss of Function	2.29	14	26.8	0.522	0.00000121	318

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00036	0.00033	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Might support glycosylation reactions in the Golgi apparatus and, when released from cells, might catalyze the hydrolysis of extracellular nucleotides. Hydrolyzes preferentially nucleoside 5'-diphosphates, nucleoside 5'-triphosphates are hydrolyzed only to a minor extent, there is no hydrolysis of nucleoside 5'-monophosphates. The order of activity with different substrates is GDP > IDP >> UDP = CDP >> ADP (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.848
RVIS EVS: 0.94
RVIS percentile EVS: 89.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.608

Gene Damage Prediction

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