PRUNE1

protein-coding

prune exopolyphosphatase 1

Gene summary

This gene encodes a member of the DHH protein superfamily of phosphoesterases. This protein has been found to function as both a nucleotide phosphodiesterase and an exopolyphosphatase. This protein is believed to stimulate cancer progression and metastases through the induction of cell motility. A pseuodgene has been identified on chromosome 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Previous symbols:

PRUNE

MANE transcript

NM_021222.3

Inheritance

ClinVar variants

P:27U:43B:46

Top phenotype

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr1:151,008,420-151,035,713

External References & Databases

Ensembl (ENSG00000143363)

Transcript & Mutation Effects

hg38 • Region Span ~27.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060490

Submitter: PanelApp Australia

neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060490

Submitter: G2P

neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060490

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060490

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomaliesAR

Manifestation: 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: 26539891; 28211990; 28334956

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRUNE1 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 117

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomaliesTotal: 26

not specifiedTotal: 14

PRUNE1-related disorderTotal: 13

Inborn genetic diseasesTotal: 10

Abnormal brain morphologyTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021222.3. 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			1 clinvar	33 clinvar	1 clinvar	35
missense	3 clinvar	5 clinvar	36 clinvar	8 clinvar	4 clinvar	56
nonsense	4 clinvar	3 clinvar	3 clinvar			10
start loss		1 clinvar				1
frameshift	5 clinvar	3 clinvar				8
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	3 clinvar			6
Total	13	14	43	41	5	116

Highest pathogenic variant AF is 0.000025405276

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021222.3	RefSeq	NP_067045.1	8	MANE Select
ENST00000271620.8	Ensembl	ENSP00000271620.3	8	MANE Select
NM_001303229.2	RefSeq	NP_001290158.1	4	Standard
NM_001303242.2	RefSeq	NP_001290171.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)

Biological Process

polyphosphate catabolic process
dephosphorylation
regulation of microtubule polymerization
regulation of neurogenesis

Molecular Function

exopolyphosphatase activity
inorganic diphosphatase activity
protein binding
tubulin binding
phosphatase activity

Cellular Component

nucleus
cytoplasm
cytosol
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000271620
Coding exons: 8
Length: 27294
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125747
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	193	242	0.799	0.0000122	2933
Missense (PolyPhen)		54	82.829	0.65195		1009
Synonymous	1.34	82	99.0	0.828	0.00000500	935
Loss of Function	2.68	7	19.9	0.352	0.00000113	220

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphodiesterase (PDE) that has higher activity toward cAMP than cGMP, as substrate. Plays a role in cell proliferation, migration and differentiation, and acts as a negative regulator of NME1. Plays a role in the regulation of neurogenesis (PubMed:28334956). Involved in the regulation of microtubule polymerization (PubMed:28334956). {ECO:0000269|PubMed:10602478, ECO:0000269|PubMed:11687967, ECO:0000269|PubMed:14998490, ECO:0000269|PubMed:16428445, ECO:0000269|PubMed:17906697, ECO:0000269|PubMed:28334956}.;

Recessive Scores

pRec: 0.139

Intolerance Scores

RVIS EVS: 0.71
RVIS percentile EVS: 85.63

Essentials

Essential (gene trap): N