PNP

Chr 14AR

purine nucleoside phosphorylase

Also known as: NP, PRO1837, PUNP

This gene encodes an enzyme which reversibly catalyzes the phosphorolysis of purine nucleosides. The enzyme is trimeric, containing three identical subunits. Mutations which result in nucleoside phosphorylase deficiency result in defective T-cell (cell-mediated) immunity but can also affect B-cell immunity and antibody responses. Neurologic disorders may also be apparent in patients with immune defects. A known polymorphism at aa position 51 that does not affect enzyme activity has been described. A pseudogene has been identified on chromosome 2. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
DNmechanismARLOEUF 1.151 OMIM phenotype
Clinical SummaryPNP
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Gene-Disease Validity (ClinGen)
purine nucleoside phosphorylase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.15LOEUF
pLI 0.000
Z-score 1.14
OE 0.68 (0.421.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.44Z-score
OE missense 0.90 (0.791.04)
146 obs / 161.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.68 (0.421.15)
00.351.4
Missense OE?0.90 (0.791.04)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 10 / 14.7Missense obs/exp: 146 / 161.7Syn Z: -0.02

This gene — mechanism propensity

DN
0.76top 25%
GOF
0.5465th %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

PNP · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Polycystic Ovary SyndromeHypothalamic Amenorrhea

Body Fat as Determinant of Female Gonadal Dysfunction

RECRUITING
NCT03841981Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalStarted 2020-01-31
Anthropometric and physical examinationIndirect calorimetry, accelerometer and seven-day dietary recallBiochemical, hormonal and metabolic phenotyping
Colitis, UlcerativeSleep QualityGastrointestinal Microbiome

Clinical Characteristics of Sleep Disorders in Patients With Ulcerative Colitis

RECRUITING
NCT06359808Xijing HospitalStarted 2024-04-01
Perimenopausal Syndrome

Clinical Efficacy Study of Jinfeng Pill in the Treatment of Perimenopausal Syndrome

RECRUITING
NCT07606755Phase PHASE4Tongji HospitalStarted 2026-05-10
Jinfeng PillPlacebo
X-Linked Chronic Granulomatous Disease

Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease

RECRUITING
NCT06876363Phase PHASE1, PHASE2EnsomaStarted 2025-08-05
EN-374
Glioma

Engineered HSV-1 M032 for the Treatment of Children and Adults With Newly Diagnosed Diffuse Midline Glioma After Standard of Care Radiation

RECRUITING
NCT07076498Phase PHASE1M.D. Anderson Cancer CenterStarted 2026-04-23
M032
Healthy VolunteersMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

RECRUITING
NCT05648214Phase PHASE1, PHASE2Regeneron PharmaceuticalsStarted 2022-12-27
ALN-PNPPlacebo (PB)