PRUNE1

Chr 1AR

prune exopolyphosphatase 1

Also known as: DRES-17, DRES17, H-PRUNE, HTCD37, NMIHBA, PRUNE

NCBI Gene: 58497 ENSG00000143363 UniProt: Q86TP1 OMIM: 617413

The protein functions as a phosphodiesterase with higher activity toward cAMP than cGMP and regulates neurogenesis and microtubule polymerization. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.661), consistent with its role in early neurodevelopment.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.661 OMIM phenotype

Clinical Summary— PRUNE1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

26 unique Pathogenic / Likely Pathogenic· 43 VUS of 147 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — PRUNE1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.009

Z-score 2.68

OE 0.35 (0.20–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.11Z-score

OE missense 0.80 (0.71–0.90)

193 obs / 241.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.20–0.66)

0≤0.351.4

Missense OE?0.80 (0.71–0.90)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 7 / 19.9Missense obs/exp: 193 / 241.7Syn Z: 1.34

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPRUNE1-related PEHO like conditionLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6356th %ile

GOF

0.5955th %ile

LOF

0.2970th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic12

VUS43

Likely Benign58

Benign11

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	3	0	0	14
Likely Pathogenic	6	6	0	0	12
VUS	3	36	3	1	43
Likely Benign	0	6	24	28	58
Benign	0	6	2	3	11
Conflicting	—				2
Total	20	57	29	32	140

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap PRUNE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →