BPNT1

Chr 1

3'(2'), 5'-bisphosphate nucleotidase 1

Also known as: HEL20, HsPIP, PIP

NCBI Gene: 10380 ENSG00000162813 UniProt: O95861

BPNT1 encodes a phosphatase that converts 3'(2')-phosphoadenosine 5'-phosphate (PAP) to AMP and hydrolyzes inositol 1,4-bisphosphate to inositol 4-phosphate, preventing toxic accumulation of PAP and participating in inositol recycling. Mutations cause autosomal recessive pontocerebellar hypoplasia type 1F, characterized by progressive microcephaly, intellectual disability, and cerebellar atrophy with onset in infancy or early childhood. The gene shows very low constraint against loss-of-function variants (pLI < 0.001), consistent with autosomal recessive inheritance.

ResearchSummary from RefSeq, UniProt

BPNT1, also called bisphosphate 3-prime-nucleotidase, or BPntase, is a member of a magnesium-dependent phosphomonoesterase family. Lithium, a major drug used to treat manic depression, acts as an uncompetitive inhibitor of BPntase. The predicted human protein is 92% identical to mouse BPntase. BPntase's physiologic role in nucleotide metabolism may be regulated by inositol signaling pathways. The inhibition of human BPntase may account for lithium-induced nephrotoxicity. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.98

Clinical Summary— BPNT1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 27 VUS of 42 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.62

OE 0.58 (0.36–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.36Z-score

OE missense 0.71 (0.61–0.82)

119 obs / 168.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.36–0.98)

0≤0.351.4

Missense OE?0.71 (0.61–0.82)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 10 / 17.2Missense obs/exp: 119 / 168.6Syn Z: 0.39

This gene — mechanism propensity

0.6648th %ile

GOF

0.6249th %ile

LOF

0.2873th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

42 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS27

Likely Benign1

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	1	1
Likely Pathogenic	0	0
VUS	27	27
Likely Benign	1	1
Benign	0	0
Total	29	29

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap BPNT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →