PURA

Chr 5

purine rich element binding protein A

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

NCBI Gene: 5813ENSG00000185129UniProt: Q00577

The protein is a sequence-specific single-stranded DNA-binding protein that binds to purine-rich elements at replication origins and gene flanking regions, controlling DNA replication and transcription. Loss-of-function mutations cause an autosomal dominant neurodevelopmental disorder characterized by neonatal respiratory insufficiency, hypotonia, and feeding difficulties. The high pLI score (0.94) indicates strong intolerance to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 0.34
Clinical Summary— PURA
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.
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ClinVar Variants
143 unique Pathogenic / Likely Pathogenic· 179 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — PURA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.00 (0.00–0.34)
0≤0.351.4
Missense OE0.25 (0.19–0.32)
0≤0.61.4
Synonymous OE1.53
0≤1.21.6
LoF obs/exp: 0 / 8.9Missense obs/exp: 39 / 158.3Syn Z: -3.51
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePURA-related intellectual disabilityLOFAD
DN
0.3296th %ile
GOF
0.3887th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 70% of P/LP variants are LoF · LOEUF 0.34

Literature Evidence

LOFRecently, haploinsufficiency of PURA has been identified as an essential cause of 5q31.3 microdeletion syndrome, which is characterized by severe psychomotor developmental delay, epilepsy, distinctive features, and delayed myelination.PMID:29619234

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic60
VUS179
Likely Benign150
Benign19
Conflicting9
83
Pathogenic
60
Likely Pathogenic
179
VUS
150
Likely Benign
19
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
68
11
4
0
83
Likely Pathogenic
32
28
0
0
60
VUS
2
134
9
34
179
Likely Benign
0
32
1
117
150
Benign
0
9
1
9
19
Conflicting
—9
Total10221415160500

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Discovery and validation of PURA as a transcription target of 20(S)-protopanaxadiol: Implications for the treatment of cognitive dysfunction
Chen F et al.·J Ginseng Res
2023
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
2025Functional
Heterozygous c.175C>T variant in PURA gene causes severe developmental delay
Noda Y et al.·Clin Case Rep
2023
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
Genome-wide epigenetic signatures facilitated the variant classification of PURA gene and uncovered the pathomechanism of PURA-related neurodevelopmental disorders.
Xiao B et al.·Genet Med
2024Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients