PNP

Chr 14AR

purine nucleoside phosphorylase

Also known as: NP, PRO1837, PUNP

NCBI Gene: 4860ENSG00000198805UniProt: P01298

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]

Primary Disease Associations & Inheritance

Immunodeficiency due to purine nucleoside phosphorylase deficiencyMIM #613179
AR
340
ClinVar variants
62
Pathogenic / LP
0.00
pLI score
5
Active trials
Clinical Summary— PNP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 125 VUS of 340 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.15LOEUF
pLI 0.000
Z-score 1.14
OE 0.68 (0.42–1.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.44Z-score
OE missense 0.90 (0.79–1.04)
146 obs / 161.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.42–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.79–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 10 / 14.7Missense obs/exp: 146 / 161.7Syn Z: -0.02

ClinVar Variant Classifications

340 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic20
VUS125
Likely Benign108
Benign29
Conflicting6
42
Pathogenic
20
Likely Pathogenic
125
VUS
108
Likely Benign
29
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
30
0
42
Likely Pathogenic
5
8
7
0
20
VUS
0
99
24
2
125
Likely Benign
0
3
58
47
108
Benign
0
1
26
2
29
Conflicting
—6
Total1511314551330

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency due to purine nucleoside phosphorylase deficiency

MIM #613179

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neuropathic Pain: Central vs. Peripheral Mechanisms.
Meacham K et al.·Curr Pain Headache Rep
2017Review
Transcutaneous Electrical Nerve Stimulation in Relieving Neuropathic Pain: Basic Mechanisms and Clinical Applications.
Mokhtari T et al.·Curr Pain Headache Rep
2020Review
Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome: Part I. Clinical overview and pathophysiology.
Anderson HJ et al.·J Am Acad Dermatol
2024Review
[Diagnostics of polyneuropathies].
Heuß D·Internist (Berl)
2020Review
A systematic review of paraneoplastic pemphigus and paraneoplastic autoimmune multiorgan syndrome: Clinical features and prognostic factors.
Zou M et al.·J Am Acad Dermatol
2025Review
Paraneoplastic pemphigus.
Yong AA et al.·Australas J Dermatol
2013Review
Mirogabalin: First Global Approval.
Deeks ED·Drugs
2019Review
[Parkinsonism-associated speech disorders].
Skripkina NA et al.·Zh Nevrol Psikhiatr Im S S Korsakova
2020
Polyneuropathies in paediatrics.
Hagberg B·Eur J Pediatr
1990Review
Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway.
Yu Y et al.·J Nanobiotechnology
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Colitis, UlcerativeSleep QualityGastrointestinal Microbiome

Clinical Characteristics of Sleep Disorders in Patients With Ulcerative Colitis

RECRUITING
NCT06359808Xijing HospitalStarted 2024-04-01
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 PHASE1Regeneron PharmaceuticalsStarted 2022-12-27
ALN-PNPPlacebo (PB)
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
Glioma

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

NOT YET RECRUITING
NCT07076498Phase PHASE1M.D. Anderson Cancer CenterStarted 2026-12-01
M032
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

External Resources

Links to major genomics databases and tools