PURA

Chr 5AD

purine rich element binding protein A

Also known as: MRD31, NEDRIHF, PUR-ALPHA, PUR1, PURALPHA

NCBI Gene: 5813ENSG00000185129UniProt: Q00577

This gene product is a sequence-specific, single-stranded DNA-binding protein. It binds preferentially to the single strand of the purine-rich element termed PUR, which is present at origins of replication and in gene flanking regions in a variety of eukaryotes from yeasts through humans. Thus, it is implicated in the control of both DNA replication and transcription. Deletion of this gene has been associated with myelodysplastic syndrome and acute myelogenous leukemia. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficultiesMIM #616158
AD
300
ClinVar variants
82
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PURA
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
82 Pathogenic / Likely Pathogenic· 141 VUS of 300 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.34LOEUF
pLI 0.940
Z-score 2.77
OE 0.00 (0.00–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
3.37Z-score
OE missense 0.25 (0.19–0.32)
39 obs / 158.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.00 (0.00–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.25 (0.19–0.32)
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.1.53
0≤1.21.6
LoF obs/exp: 0 / 8.9Missense obs/exp: 39 / 158.3Syn Z: -3.51

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic34
VUS141
Likely Benign59
Benign15
Conflicting3
48
Pathogenic
34
Likely Pathogenic
141
VUS
59
Likely Benign
15
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
9
15
0
48
Likely Pathogenic
12
14
8
0
34
VUS
1
87
19
34
141
Likely Benign
0
9
8
42
59
Benign
0
6
0
9
15
Conflicting
—3
Total371255085300

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

View in ClinVar →

Protein Context — Lollipop Plot

PURA · protein map & ClinVar variants

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

Gene2Phenotype Curations

PURA-related intellectual disability

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties

MIM #616158

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PURA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
Neuromuscular and Neuromuscular Junction Manifestations of the PURA-NDD: A Systematic Review of the Reported Symptoms and Potential Treatment Options.
Mroczek M et al.·Int J Mol Sci
2023Review
PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature.
Reijnders MRF et al.·J Med Genet
2018Review
PURA-related neurodevelopmental disorders: a systematic review on genotype-phenotype correlations.
Taniguchi N et al.·J Med Genet
2025Review
PURA-Related Neurodevelopmental Disorders with Epilepsy Treated with Ketogenic Diet: A Case-Based Review.
Falsaperla R et al.·Genes (Basel)
2024Review
Differences in manifestations of epilepsy and developmental delay in PURA syndrome and 5q31 microdeletions.
Kofoed AWS et al.·Clin Genet
2024Review
A new case with the recurrent PURA p.(Phe233del) pathogenic variant: Expansion of the phenotype and review of the literature.
Ben Issa A et al.·Int J Dev Neurosci
2023Review
Genotype-phenotype variations in PURA syndrome: Asian and non-Asian perspectives from a systematic review.
Liu SN et al.·Orphanet J Rare Dis
2025Review
[Congenital Myasthenic Syndromes].
Ohno K·Brain Nerve
2024
Genome-wide CRISPR/Cas9 screening identifies a targetable MEST-PURA interaction in cancer metastasis.
Xu WW et al.·EBioMedicine
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Facial hair whorl location, behavior, and ocular temperature as a physiological stress indicator in young Pura Raza Española dressage horses.
Valera M et al.·Front Vet Sci
2026🔓 Open Access
Exploring molecular signatures in PURA syndrome using muscle proteomics and serum biomarkers.
Mroczek M et al.·J Neurol
2026🔓 Open Access
A novel frameshift variant in PURA syndrome: role of NMD pathway in disease mechanism.
Yang H et al.·Gene
2026Functional
PURA protein mislocalisation in the nucleus: mechanistic basis for transcriptional dysregulation and DNA unwinding deficits in a model of the p.L148Wfs*77 PURA variant.
Wang Y et al.·J Med Genet
2025🔓 Open AccessFunctional
The Role of Genetic and Environmental Factors in White Leg Markings: Prevalence and Heritability Analysis in Pura Raza Española Horses.
Encina A et al.·Life (Basel)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools