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…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficultiesMIM #616158

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · complex neurodevelopmental disorder · AD · ClinGen 2018
Definitive · PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation · AD · G2P

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.34

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in PURA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,100

208 rare PASS variants

Rare truncating (LoF)

1 in 69,000

5 rare PASS variants

Rare synonymous (reference)

1 in 220

274 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PURA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,100	1 in 57,000
South Asian	~43k	1 in 940	none seen
Remaining (unassigned)	~30k	1 in 2,500	none seen
European (Finnish)	~27k	1 in 810	none seen
Admixed American	~22k	1 in 1,600	none seen
African / African American	~21k	1 in 500	none seen
East Asian	~20k	1 in 1,000	none seen
Ashkenazi Jewish	~13k	≈ 1 in 5,200	none seen
Middle Eastern	~2,884	≈ 1 in 2,900	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓