Perrault syndrome 5
diseaseOn this page
Also known as Perrault syndrome caused by mutation in TWNKPerrault syndrome type 5PRLTS5TWNK Perrault syndrome
Summary
Perrault syndrome 5 (MONDO:0014504) is a disease caused by TWNK (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: TWNK (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 24
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Perrault syndrome 5 |
| Mondo ID | MONDO:0014504 |
| OMIM | 616138 |
| UMLS | C4015307 |
| MedGen | 863744 |
| GARD | 0016062 |
| Is cancer (heuristic) | no |
Also known as: Perrault syndrome 5 · Perrault syndrome caused by mutation in TWNK · Perrault syndrome type 5 · PRLTS5 · TWNK Perrault syndrome
Data availability: 24 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › Perrault syndrome › Perrault syndrome 5
Related subtypes (6): Perrault syndrome 1, Perrault syndrome 3, Perrault syndrome 2, Perrault syndrome 4, Perrault syndrome 6, Perrault syndrome 7
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
24 retrieved; paginated sample, class counts are floors:
11 conflicting classifications of pathogenicity, 6 uncertain significance, 4 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 162049 | NM_021830.5(TWNK):c.1754A>G (p.Asn585Ser) | TWNK | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 162050 | NM_021830.5(TWNK):c.1321T>G (p.Trp441Gly) | TWNK | Pathogenic | criteria provided, single submitter |
| 3377475 | NM_021830.5(TWNK):c.742_745del (p.Phe248fs) | TWNK | Pathogenic | criteria provided, single submitter |
| 3382359 | NM_021830.5(TWNK):c.1399C>T (p.Gln467Ter) | TWNK | Likely pathogenic | criteria provided, single submitter |
| 3601957 | NM_021830.5(TWNK):c.42del (p.Leu14fs) | TWNK | Likely pathogenic | criteria provided, single submitter |
| 4619 | NM_021830.5(TWNK):c.1422G>A (p.Trp474Ter) | TWNK | Likely pathogenic | criteria provided, single submitter |
| 4820080 | NM_021830.5(TWNK):c.1278_1279del (p.Ser426fs) | TWNK | Likely pathogenic | criteria provided, single submitter |
| 1309254 | NM_021830.5(TWNK):c.193C>T (p.Arg65Trp) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1344254 | NM_021830.5(TWNK):c.478C>T (p.Arg160Ter) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1497932 | NM_021830.5(TWNK):c.1618G>A (p.Gly540Arg) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 162048 | NM_021830.5(TWNK):c.1172G>A (p.Arg391His) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 162051 | NM_021830.5(TWNK):c.1519G>A (p.Val507Ile) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1683933 | NM_021830.5(TWNK):c.1958C>T (p.Ser653Phe) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 214174 | NM_021830.5(TWNK):c.737A>G (p.Asn246Ser) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 214178 | NM_021830.5(TWNK):c.1975G>A (p.Ala659Thr) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 488187 | NM_021830.5(TWNK):c.874C>A (p.Pro292Thr) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 694394 | NM_021830.5(TWNK):c.793C>T (p.Arg265Cys) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 878940 | NM_021830.5(TWNK):c.1597G>A (p.Ala533Thr) | TWNK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1312836 | NM_021830.5(TWNK):c.1338C>G (p.Ile446Met) | TWNK | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1441023 | NM_021830.5(TWNK):c.602C>T (p.Ala201Val) | TWNK | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1496673 | NM_021830.5(TWNK):c.1190A>G (p.Asp397Gly) | TWNK | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2960437 | NM_021830.5(TWNK):c.1817C>G (p.Ser606Cys) | TWNK | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3590126 | NM_021830.5(TWNK):c.250T>G (p.Phe84Val) | TWNK | Uncertain significance | criteria provided, single submitter |
| 878124 | NM_021830.5(TWNK):c.-592C>T | TWNK | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 10 · Orphanet: 6 · 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 |
|---|---|---|---|---|
| TWNK | Definitive | Autosomal recessive | Perrault syndrome 5 | 10 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TWNK | Orphanet:1186 | Infantile-onset spinocerebellar ataxia |
| TWNK | Orphanet:254892 | Autosomal dominant progressive external ophthalmoplegia |
| TWNK | Orphanet:363534 | Mitochondrial DNA depletion syndrome, hepatocerebrorenal form |
| TWNK | Orphanet:642945 | Perrault syndrome type 1 |
| TWNK | Orphanet:642976 | Perrault syndrome type 2 |
| TWNK | Orphanet:70595 | Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome |
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 |
|---|---|---|---|---|---|
| TWNK | HGNC:1160 | ENSG00000107815 | Q96RR1 | Twinkle mtDNA helicase | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TWNK | Twinkle mtDNA helicase | Mitochondrial helicase involved in mtDNA replication and repair. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
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 |
|---|---|---|---|
| Enzyme (other) | 1 | 12.0× | 0.083 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TWNK | Enzyme (other) | yes | 3.6.4.12 | DNA_helicase_DnaB-like_C, Twinkle-like, P-loop_NTPase |
Expression context
Cohort genes with no expression data: 0.
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 |
|---|---|
| gastrocnemius | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| tendon of biceps brachii | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TWNK | 211 | ubiquitous | yes | male germ line stem cell (sensu Vertebrata) in testis, tendon of biceps brachii, gastrocnemius |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TWNK | 1,390 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TWNK | Q96RR1 | 2 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways 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.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Strand-asynchronous mitochondrial DNA replication | 1 | 1142.0× | 0.003 | TWNK |
| Transcriptional activation of mitochondrial biogenesis | 1 | 203.9× | 0.007 | TWNK |
| Mitochondrial protein degradation | 1 | 114.2× | 0.009 | TWNK |
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 |
|---|---|---|---|---|
| mitochondrial transcription | 1 | 2407.4× | 9e-04 | TWNK |
| mitochondrial DNA replication | 1 | 1532.0× | 9e-04 | TWNK |
| protein hexamerization | 1 | 1404.3× | 9e-04 | TWNK |
| DNA-templated DNA replication | 1 | 561.7× | 0.002 | TWNK |
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 |
|---|---|---|
| TWNK | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| TWNK | 3.6.4.12 | DNA helicase |
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 | 1 | TWNK |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
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) |
|---|---|---|
| TWNK | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: TWNK