High-grade astrocytoma with piloid features

Summary

High-grade astrocytoma with piloid features (MONDO:0858958) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	high-grade astrocytoma with piloid features
Mondo ID	MONDO:0858958
DOID	DOID:0081304
NCIT	C185879
UMLS	C5670122
MedGen	1812304
GARD	0026637
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › nervous system neoplasm › neuroepithelial neoplasm › glioma › astrocytic tumor › high grade astrocytic tumor › anaplastic astrocytoma › high-grade astrocytoma with piloid features

Related subtypes (2): IDH-mutant anaplastic astrocytoma, IDH-wildtype anaplastic astrocytoma

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2573128	NM_015450.3(POT1):c.910dup (p.Asp304fs)	POT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
412075	NM_177438.3(DICER1):c.3713T>C (p.Leu1238Pro)	DICER1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DICER1	Orphanet:276399	Familial multinodular goiter
DICER1	Orphanet:284343	DICER1 tumor-predisposition syndrome
DICER1	Orphanet:404476	Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome
DICER1	Orphanet:99757	Embryonal rhabdomyosarcoma
DICER1	Orphanet:99914	Gynandroblastoma
DICER1	Orphanet:99915	Malignant granulosa cell tumor of the ovary
DICER1	Orphanet:99916	Malignant Sertoli-Leydig cell tumor of the ovary
POT1	Orphanet:251627	Oligodendroglioma
POT1	Orphanet:251630	Anaplastic oligodendroglioma
POT1	Orphanet:618	Familial melanoma
POT1	Orphanet:67038	B-cell chronic lymphocytic leukemia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DICER1	HGNC:17098	ENSG00000100697	Q9UPY3	Endoribonuclease Dicer	clinvar
POT1	HGNC:17284	ENSG00000128513	Q9NUX5	Protection of telomeres protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DICER1	Endoribonuclease Dicer	Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing.
POT1	Protection of telomeres protein 1	Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.

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)
DICER1	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, Helicase_C-like, PAZ_dom
POT1	Other/Unknown	no		Telomer_end-bd_POT1/Cdc13, NA-bd_OB-fold, POT1

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caput epididymis	1
cauda epididymis	1
tongue squamous epithelium	1
calcaneal tendon	1
germinal epithelium of ovary	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DICER1	295	ubiquitous	marker	cauda epididymis, caput epididymis, tongue squamous epithelium
POT1	279	ubiquitous	marker	secondary oocyte, germinal epithelium of ovary, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DICER1	8,268
POT1	1,842

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DICER1	Q9UPY3	21
POT1	Q9NUX5	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis	1	1903.3×	0.009	DICER1
Small interfering RNA (siRNA) biogenesis	1	571.0×	0.009	DICER1
Telomere C-strand synthesis initiation	1	407.9×	0.009	POT1
Processive synthesis on the C-strand of the telomere	1	380.7×	0.009	POT1
Telomere C-strand (Lagging Strand) Synthesis	1	380.7×	0.009	POT1
Removal of the Flap Intermediate from the C-strand	1	317.2×	0.009	POT1
Regulation of MITF-M-dependent genes involved in apoptosis	1	317.2×	0.009	DICER1
Telomere Extension By Telomerase	1	228.4×	0.009	POT1
MicroRNA (miRNA) biogenesis	1	228.4×	0.009	DICER1
Polymerase switching on the C-strand of the telomere	1	211.5×	0.009	POT1
M-decay: degradation of maternal mRNAs by maternally stored factors	1	163.1×	0.011	DICER1
Packaging Of Telomere Ends	1	109.8×	0.013	POT1
Recognition and association of DNA glycosylase with site containing an affected purine	1	102.0×	0.013	POT1
Cleavage of the damaged purine	1	102.0×	0.013	POT1
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	1	92.1×	0.013	POT1
Cleavage of the damaged pyrimidine	1	92.1×	0.013	POT1
Inhibition of DNA recombination at telomere	1	84.0×	0.013	POT1
DNA Damage/Telomere Stress Induced Senescence	1	81.6×	0.013	POT1
Meiotic synapsis	1	70.5×	0.014	POT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of DNA strand elongation	1	8426.0×	0.002	POT1
positive regulation of telomeric D-loop disassembly	1	8426.0×	0.002	POT1
positive regulation of Schwann cell differentiation	1	4213.0×	0.002	DICER1
peripheral nervous system myelin formation	1	2808.7×	0.002	DICER1
global gene silencing by mRNA cleavage	1	2808.7×	0.002	DICER1
telomere assembly	1	2106.5×	0.002	POT1
tRNA decay	1	1685.2×	0.002	DICER1
regulation of double-strand break repair via nonhomologous end joining	1	1685.2×	0.002	POT1
regulation of telomere maintenance via telomerase	1	1404.3×	0.002	POT1
negative regulation of Schwann cell proliferation	1	1203.7×	0.002	DICER1
establishment of protein localization to telomere	1	1053.2×	0.002	POT1
siRNA processing	1	936.2×	0.002	DICER1
telomeric D-loop disassembly	1	936.2×	0.002	POT1
RISC complex assembly	1	766.0×	0.003	DICER1
miRNA metabolic process	1	702.2×	0.003	DICER1
telomere capping	1	648.1×	0.003	POT1
apoptotic DNA fragmentation	1	601.9×	0.003	DICER1
pre-miRNA processing	1	561.7×	0.003	DICER1
miRNA processing	1	526.6×	0.003	DICER1
nerve development	1	468.1×	0.003	DICER1
positive regulation of myelination	1	383.0×	0.003	DICER1
telomere maintenance via telomerase	1	366.4×	0.003	POT1
negative regulation of telomere maintenance via telomerase	1	366.4×	0.003	POT1
positive regulation of telomere maintenance via telomerase	1	366.4×	0.003	POT1
positive regulation of telomere maintenance	1	255.3×	0.005	POT1
negative regulation of tumor necrosis factor-mediated signaling pathway	1	227.7×	0.005	DICER1
neuron projection morphogenesis	1	138.1×	0.008	DICER1
negative regulation of tumor necrosis factor production	1	125.8×	0.009	DICER1
negative regulation of gene expression	1	34.5×	0.030	DICER1
negative regulation of transcription by RNA polymerase II	1	8.9×	0.110	DICER1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DICER1	0	0
POT1	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
DICER1	8	Binding:8
POT1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DICER1	3.1.26.3	ribonuclease III

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	DICER1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	POT1

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)
DICER1	8	—
POT1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.