PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation
diseaseOn this page
Also known as autosomal dominant intellectual disability 31intellectual disability, autosomal dominant 31intellectual disability, autosomal dominant type 31mental retardation, autosomal dominant 31mental retardation, autosomal dominant type 31MRD31neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficultiesPURA syndrome
Summary
PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation (MONDO:0014512) is a disease caused by PURA (GenCC Definitive), with 1 cohort gene.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: PURA (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 6
- Phenotypes (HPO): 38
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 24 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Signs & symptoms
Clinical features (HPO)
38 HPO clinical features (Orphanet curated; top 38 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0001250 | Seizure | Very frequent (80-99%) |
| HP:0001263 | Global developmental delay | Very frequent (80-99%) |
| HP:0002098 | Respiratory distress | Very frequent (80-99%) |
| HP:0008872 | Feeding difficulties in infancy | Very frequent (80-99%) |
| HP:0002058 | Myopathic facies | Frequent (30-79%) |
| HP:0011344 | Severe global developmental delay | Frequent (30-79%) |
| HP:0000218 | High palate | Occasional (5-29%) |
| HP:0000219 | Thin upper lip vermilion | Occasional (5-29%) |
| HP:0000252 | Microcephaly | Occasional (5-29%) |
| HP:0000276 | Long face | Occasional (5-29%) |
| HP:0000286 | Epicanthus | Occasional (5-29%) |
| HP:0000293 | Full cheeks | Occasional (5-29%) |
| HP:0000297 | Facial hypotonia | Occasional (5-29%) |
| HP:0000324 | Facial asymmetry | Occasional (5-29%) |
| HP:0000348 | High forehead | Occasional (5-29%) |
| HP:0000377 | Abnormal pinna morphology | Occasional (5-29%) |
| HP:0000430 | Underdeveloped nasal alae | Occasional (5-29%) |
| HP:0000431 | Wide nasal bridge | Occasional (5-29%) |
| HP:0000455 | Broad nasal tip | Occasional (5-29%) |
| HP:0000463 | Anteverted nares | Occasional (5-29%) |
| HP:0000506 | Telecanthus | Occasional (5-29%) |
| HP:0000545 | Myopia | Occasional (5-29%) |
| HP:0000582 | Upslanted palpebral fissure | Occasional (5-29%) |
| HP:0000637 | Long palpebral fissure | Occasional (5-29%) |
| HP:0000736 | Short attention span | Occasional (5-29%) |
| HP:0000739 | Anxiety | Occasional (5-29%) |
| HP:0001251 | Ataxia | Occasional (5-29%) |
| HP:0001332 | Dystonia | Occasional (5-29%) |
| HP:0002007 | Frontal bossing | Occasional (5-29%) |
| HP:0002136 | Broad-based gait | Occasional (5-29%) |
| HP:0002267 | Exaggerated startle response | Occasional (5-29%) |
| HP:0006481 | Abnormality of primary teeth | Occasional (5-29%) |
| HP:0006829 | Severe muscular hypotonia | Occasional (5-29%) |
| HP:0010804 | Tented upper lip vermilion | Occasional (5-29%) |
| HP:0011081 | Incisor macrodontia | Occasional (5-29%) |
| HP:0011220 | Prominent forehead | Occasional (5-29%) |
| HP:0012899 | Handgrip myotonia | Occasional (5-29%) |
| HP:0100660 | Dyskinesia | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation |
| Mondo ID | MONDO:0014512 |
| OMIM | 616158 |
| Orphanet | 438216 |
| DOID | DOID:0070061 |
| GARD | 0017740 |
| Is cancer (heuristic) | no |
Also known as: autosomal dominant intellectual disability 31 · intellectual disability, autosomal dominant 31 · intellectual disability, autosomal dominant type 31 · mental retardation, autosomal dominant 31 · mental retardation, autosomal dominant type 31 · MRD31 · neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties · PURA syndrome · PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation
Data availability: 6 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome › PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation
Related subtypes (1): severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
6 retrieved; paginated sample, class counts are floors:
4 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1299583 | NM_005859.5(PURA):c.531del (p.Pro178fs) | PURA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1699169 | NM_005859.5(PURA):c.362dup (p.Tyr121Ter) | PURA | Pathogenic | criteria provided, single submitter |
| 1805833 | NM_005859.5(PURA):c.62del (p.Leu21fs) | PURA | Pathogenic | criteria provided, single submitter |
| 421477 | NM_005859.5(PURA):c.572C>T (p.Pro191Leu) | PURA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 432233 | NM_005859.5(PURA):c.159dup (p.Leu54fs) | PURA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2500903 | NM_005859.5(PURA):c.273_328del (p.Gly92fs) | PURA | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| PURA | Definitive | Autosomal dominant | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PURA | Orphanet:314655 | Severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion |
| PURA | Orphanet:438216 | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PURA | HGNC:9701 | ENSG00000185129 | Q00577 | Transcriptional activator protein Pur-alpha | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PURA | Transcriptional activator protein Pur-alpha | This is a probable transcription activator that specifically binds the purine-rich single strand of the PUR element located upstream of the MYC gene. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PURA | Other/Unknown | no | PUR-bd_fam |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| Brodmann (1909) area 23 | 1 |
| choroid plexus epithelium | 1 |
| middle temporal gyrus | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PURA | 295 | ubiquitous | marker | Brodmann (1909) area 23, middle temporal gyrus, choroid plexus epithelium |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PURA | 1,483 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PURA | Q00577 | 4 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| dendritic transport of messenger ribonucleoprotein complex | 1 | 5617.3× | 0.001 | PURA |
| lymphocyte proliferation | 1 | 2407.4× | 0.002 | PURA |
| DNA replication initiation | 1 | 624.1× | 0.004 | PURA |
| epithelial cell proliferation | 1 | 312.1× | 0.006 | PURA |
| nervous system development | 1 | 45.9× | 0.035 | PURA |
| positive regulation of cell population proliferation | 1 | 33.6× | 0.040 | PURA |
| negative regulation of transcription by RNA polymerase II | 1 | 17.7× | 0.064 | PURA |
| regulation of transcription by RNA polymerase II | 1 | 11.7× | 0.086 | PURA |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PURA | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | PURA |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PURA | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: PURA