Leukodystrophy, hypomyelinating, 21
disease diseaseOn this page
Also known as HLD21
Summary
Leukodystrophy, hypomyelinating, 21 (MONDO:0030263) is a disease caused by POLR3K (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: POLR3K (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 5
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | leukodystrophy, hypomyelinating, 21 |
| Mondo ID | MONDO:0030263 |
| OMIM | 619310 |
| DOID | DOID:0070407 |
| UMLS | C5543334 |
| MedGen | 1778269 |
| GARD | 0025525 |
| Is cancer (heuristic) | no |
Also known as: HLD21 · leukodystrophy, hypomyelinating, 21
Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › leukodystrophy › POLR-related leukodystrophy › POLR3-related leukodystrophy › leukodystrophy, hypomyelinating, 21
Related subtypes (3): leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, hypomyelinating leukodystrophy 11
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
5 retrieved; paginated sample, class counts are floors:
3 pathogenic, 2 uncertain significance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2499509 | NC_000016.10:g.(30362_?)_(?_48162)del | LOC130058083 | Pathogenic | criteria provided, single submitter |
| 1065610 | NM_016310.5(POLR3K):c.121C>T (p.Arg41Trp) | POLR3K | Pathogenic | no assertion criteria provided |
| 2499507 | NM_016310.5(POLR3K):c.322G>T (p.Asp108Tyr) | POLR3K | Pathogenic | criteria provided, single submitter |
| 2435164 | NM_016310.5(POLR3K):c.122G>A (p.Arg41Gln) | POLR3K | Uncertain significance | criteria provided, single submitter |
| 2435165 | NM_016310.5(POLR3K):c.95ACA[1] (p.Asn33del) | POLR3K | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 3 · Orphanet: 0 · 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 |
|---|---|---|---|---|
| POLR3K | Strong | Autosomal recessive | leukodystrophy, hypomyelinating, 21 | 3 |
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 |
|---|---|---|---|---|---|
| POLR3K | HGNC:14121 | ENSG00000161980 | Q9Y2Y1 | DNA-directed RNA polymerase III subunit RPC10 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| POLR3K | DNA-directed RNA polymerase III subunit RPC10 | Core component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates. |
Protein-family classification
Druggable: 0 · Difficult: 1 · Unknown: 0 · 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 |
|---|---|---|---|
| Transcription factor | 1 | 8.3× | 0.121 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| POLR3K | Transcription factor | no | Znf_TFIIS, Zn_ribbon_RPB9, Rpa12/Rpb9/Rpc10/TFS |
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 |
|---|---|
| mucosa of transverse colon | 1 |
| prefrontal cortex | 1 |
| primordial germ cell in gonad | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| POLR3K | 277 | ubiquitous | marker | mucosa of transverse colon, prefrontal cortex, primordial germ cell in gonad |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| POLR3K | 2,332 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| POLR3K | Q9Y2Y1 | 29 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 12. 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 |
|---|---|---|---|---|
| RNA Polymerase III Chain Elongation | 1 | 634.4× | 0.005 | POLR3K |
| RNA Polymerase III Transcription Termination | 1 | 496.5× | 0.005 | POLR3K |
| RNA Polymerase III Transcription Initiation From Type 2 Promoter | 1 | 423.0× | 0.005 | POLR3K |
| RNA Polymerase III Transcription Initiation From Type 1 Promoter | 1 | 407.9× | 0.005 | POLR3K |
| RNA Polymerase III Transcription Initiation From Type 3 Promoter | 1 | 407.9× | 0.005 | POLR3K |
| RNA Polymerase III Transcription Initiation | 1 | 335.9× | 0.005 | POLR3K |
| RNA Polymerase III Transcription | 1 | 326.3× | 0.005 | POLR3K |
| Cytosolic sensors of pathogen-associated DNA | 1 | 285.5× | 0.005 | POLR3K |
| RNA Polymerase III Abortive And Retractive Initiation | 1 | 278.5× | 0.005 | POLR3K |
| Innate Immune System | 1 | 25.5× | 0.047 | POLR3K |
| Gene expression (Transcription) | 1 | 17.8× | 0.061 | POLR3K |
| Immune System | 1 | 13.0× | 0.077 | POLR3K |
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 |
|---|---|---|---|---|
| transcription by RNA polymerase III | 1 | 766.0× | 0.004 | POLR3K |
| defense response to virus | 1 | 69.3× | 0.022 | POLR3K |
| innate immune response | 1 | 33.6× | 0.030 | POLR3K |
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 |
|---|---|---|
| POLR3K | 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 | POLR3K |
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) |
|---|---|---|
| POLR3K | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: POLR3K