PURA

Chr 5AD

purine rich element binding protein A

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

NCBI Gene: 5813 ENSG00000185129 UniProt: Q00577 OMIM: 600473

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.341 OMIM phenotype

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

221 unique Pathogenic / Likely Pathogenic· 190 VUS of 630 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — PURA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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 OE?0.00 (0.00–0.34)

0≤0.351.4

Missense OE?0.25 (0.19–0.32)

0≤0.61.4

Synonymous OE?1.53

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

This gene — mechanism propensity

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 · 67% of P/LP variants are LoF · LOEUF 0.34 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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.1

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

References

1.PMID 29619234 ↗

ClinVar Variant Classifications

630 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic131

Likely Pathogenic90

VUS190

Likely Benign180

Benign20

Conflicting18

131

Pathogenic

Likely Pathogenic

190

VUS

180

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	107	22	2	0	131
Likely Pathogenic	42	48	0	0	90
VUS	2	147	7	34	190
Likely Benign	0	43	1	136	180
Benign	0	10	1	9	20
Conflicting	—				18
Total	151	270	11	179	629

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap PURA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →