Perrault syndrome 4
diseaseOn this page
Also known as LARS2 Perrault syndromePerrault syndrome caused by mutation in LARS2Perrault syndrome type 4PRLTS4
Summary
Perrault syndrome 4 (MONDO:0014126) is a disease caused by LARS2 (GenCC Strong), with 2 cohort genes.
At a glance
- Causal gene: LARS2 (GenCC Strong)
- Cohort genes: 2
- ClinVar variants: 55
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Perrault syndrome 4 |
| Mondo ID | MONDO:0014126 |
| OMIM | 615300 |
| UMLS | C3809105 |
| MedGen | 815435 |
| GARD | 0015943 |
| Is cancer (heuristic) | no |
Also known as: LARS2 Perrault syndrome · Perrault syndrome 4 · Perrault syndrome caused by mutation in LARS2 · Perrault syndrome type 4 · PRLTS4
Data availability: 55 ClinVar variants · 2 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 recessive disease › Perrault syndrome › Perrault syndrome 4
Related subtypes (6): Perrault syndrome 1, Perrault syndrome 3, Perrault syndrome 2, Perrault syndrome 5, 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
55 retrieved; paginated sample, class counts are floors:
12 pathogenic, 12 uncertain significance, 11 likely pathogenic, 7 benign, 6 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 427986 | NM_015340.3(LARS2):c.[1912G>A];[899C>T] | Pathogenic | criteria provided, single submitter | |
| 1185630 | NM_015340.4(LARS2):c.1783del (p.Ala595fs) | LARS2 | Pathogenic | no assertion criteria provided |
| 1185680 | NM_015340.4(LARS2):c.41_42del (p.Leu14fs) | LARS2 | Pathogenic | no assertion criteria provided |
| 1342701 | NM_015340.4(LARS2):c.1670A>G (p.Tyr557Cys) | LARS2 | Pathogenic | no assertion criteria provided |
| 191173 | NM_015340.4(LARS2):c.457A>C (p.Asn153His) | LARS2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 203991 | NM_015340.4(LARS2):c.1912G>A (p.Glu638Lys) | LARS2 | Pathogenic | criteria provided, single submitter |
| 2720074 | NM_015340.4(LARS2):c.1249A>G (p.Met417Val) | LARS2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3601183 | NM_015340.4(LARS2):c.1239+1G>A | LARS2 | Pathogenic | criteria provided, single submitter |
| 3601186 | NM_015340.4(LARS2):c.1498G>T (p.Glu500Ter) | LARS2 | Pathogenic | criteria provided, single submitter |
| 3601187 | NM_015340.4(LARS2):c.1623-1G>T | LARS2 | Pathogenic | criteria provided, single submitter |
| 3601188 | NM_015340.4(LARS2):c.2218del (p.Thr740fs) | LARS2 | Pathogenic | criteria provided, single submitter |
| 3601190 | NM_015340.4(LARS2):c.2585_2589dup (p.Asp864fs) | LARS2 | Pathogenic | criteria provided, single submitter |
| 431124 | NM_015340.4(LARS2):c.1987C>T (p.Arg663Trp) | LARS2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 431125 | NM_015340.4(LARS2):c.371A>T (p.Asn124Ile) | LARS2 | Pathogenic | criteria provided, single submitter |
| 55871 | NM_015340.4(LARS2):c.1565C>A (p.Thr522Asn) | LARS2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 55872 | NM_015340.4(LARS2):c.1886C>T (p.Thr629Met) | LARS2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 55873 | NM_015340.4(LARS2):c.1077del (p.Ile360fs) | LARS2 | Pathogenic | criteria provided, single submitter |
| 992952 | NM_015340.4(LARS2):c.880G>A (p.Glu294Lys) | LARS2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1708965 | NM_015340.4(LARS2):c.2072G>A (p.Trp691Ter) | LARS2 | Likely pathogenic | criteria provided, single submitter |
| 2446359 | NM_015340.4(LARS2):c.1079T>C (p.Ile360Thr) | LARS2 | Likely pathogenic | criteria provided, single submitter |
| 3242248 | NM_015340.4(LARS2):c.795A>G (p.Ile265Met) | LARS2 | Likely pathogenic | criteria provided, single submitter |
| 3382175 | NM_015340.4(LARS2):c.620G>A (p.Trp207Ter) | LARS2 | Likely pathogenic | criteria provided, single submitter |
| 3601182 | NM_015340.4(LARS2):c.1193T>C (p.Ile398Thr) | LARS2 | Likely pathogenic | criteria provided, single submitter |
| 3601184 | NM_015340.4(LARS2):c.1334_1335del (p.Lys445fs) | LARS2 | Likely pathogenic | criteria provided, single submitter |
| 3601189 | NM_015340.4(LARS2):c.235-2A>G | LARS2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 623147 | NM_015340.4(LARS2):c.1115C>G (p.Ser372Ter) | LARS2 | Likely pathogenic | criteria provided, single submitter |
| 691519 | NM_015340.4(LARS2):c.683G>A (p.Arg228His) | LARS2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 691523 | NM_015340.4(LARS2):c.440A>C (p.Gln147Pro) | LARS2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 691524 | NM_015340.4(LARS2):c.1607C>T (p.Pro536Leu) | LARS2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1916104 | NM_015340.4(LARS2):c.764C>T (p.Ala255Val) | LARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · Orphanet: 3 · 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 |
|---|---|---|---|---|
| LARS2 | Strong | Autosomal recessive | Perrault syndrome 4 | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| LARS2 | Orphanet:528091 | Hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome |
| LARS2 | Orphanet:642945 | Perrault syndrome type 1 |
| LARS2 | Orphanet:642976 | Perrault syndrome type 2 |
Cohort genes → proteins
2 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| LARS2 | HGNC:17095 | ENSG00000011376 | Q15031 | Leucine–tRNA ligase, mitochondrial | gencc,clinvar |
| LARS2-AS1 | HGNC:40796 | ENSG00000232455 | LARS2 antisense RNA 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| LARS2 | Leucine–tRNA ligase, mitochondrial | Catalyzes the attachment of leucine to its cognate tRNA. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5
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 | 6.0× | 0.320 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| LARS2 | Enzyme (other) | yes | 6.1.1.4 | aa-tRNA-synth_I_CS, aa-tRNA-synth_Ia, Leu-tRNA-ligase |
| LARS2-AS1 | Other/Unknown | no |
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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| adrenal tissue | 1 |
| oocyte | 1 |
| ventricular zone | 1 |
| hindlimb stylopod muscle | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| primordial germ cell in gonad | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| LARS2 | 285 | ubiquitous | yes | ventricular zone, oocyte, adrenal tissue |
| LARS2-AS1 | 108 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle, primordial germ cell in gonad |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LARS2 | 3,406 |
| LARS2-AS1 | 0 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 1
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| LARS2 | Q15031 | 90.57 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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 |
|---|---|---|---|---|
| Mitochondrial tRNA aminoacylation | 1 | 519.1× | 0.007 | LARS2 |
| tRNA Aminoacylation | 1 | 285.5× | 0.007 | LARS2 |
| Translation | 1 | 62.1× | 0.021 | LARS2 |
| Metabolism of proteins | 1 | 12.4× | 0.081 | LARS2 |
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 |
|---|---|---|---|---|
| leucyl-tRNA aminoacylation | 1 | 8426.0× | 4e-04 | LARS2 |
| tRNA aminoacylation for protein translation | 1 | 842.6× | 0.002 | LARS2 |
| mitochondrial translation | 1 | 173.7× | 0.006 | LARS2 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| LARS2 | 0 | 0 |
| LARS2-AS1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| LARS2 | 1 | ADMET:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| LARS2 | 6.1.1.4 | leucine-tRNA ligase |
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 | 1 | LARS2 |
| E | Difficult family or no structure, no drug | 1 | LARS2-AS1 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| LARS2 | 1 | — |
| LARS2-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.