BPNT1

Chr 1

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

Also known as: HEL20, HsPIP, PIP

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.98
Clinical SummaryBPNT1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.62
OE 0.58 (0.360.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.36Z-score
OE missense 0.71 (0.610.82)
119 obs / 168.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.360.98)
00.351.4
Missense OE0.71 (0.610.82)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 10 / 17.2Missense obs/exp: 119 / 168.6Syn Z: 0.39
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BPNT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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