Anauxetic dysplasia 2

Summary

Anauxetic dysplasia 2 (MONDO:0054561) is a disease caused by POP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: POP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anauxetic dysplasia 2
Mondo ID	MONDO:0054561
OMIM	617396
DOID	DOID:0080962
UMLS	C4479357
MedGen	1384439
GARD	0025949
Is cancer (heuristic)	no

Also known as: anauxetic dysplasia 2 · ANXD2

Data availability: 12 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › spondyloepiphyseal dysplasia › anauxetic dysplasia › anauxetic dysplasia 2

Related subtypes (2): anauxetic dysplasia 3, anauxetic dysplasia 1

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

12 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 4 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
393588	NM_001145860.2(POP1):c.1573C>T (p.Pro525Ser)	POP1	Pathogenic	no assertion criteria provided
417736	NM_001145860.2(POP1):c.1744C>T (p.Pro582Ser)	POP1	Pathogenic	no assertion criteria provided
417737	NM_001145860.2(POP1):c.2607del (p.Glu870fs)	POP1	Pathogenic	no assertion criteria provided
417738	NM_001145860.2(POP1):c.1531G>T (p.Asp511Tyr)	POP1	Pathogenic	no assertion criteria provided
1332833	NM_001145860.2(POP1):c.2087T>A (p.Val696Asp)	POP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3068111	NM_001145860.2(POP1):c.486+2T>C	POP1	Likely pathogenic	criteria provided, single submitter
1029341	NM_001145860.2(POP1):c.1537C>T (p.Arg513Ter)	POP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1431906	NM_001145860.2(POP1):c.580C>T (p.Arg194Cys)	POP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3596010	NM_001145860.2(POP1):c.292A>G (p.Ile98Val)	POP1	Uncertain significance	criteria provided, single submitter
393589	NM_001145860.2(POP1):c.1748G>A (p.Gly583Glu)	POP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4532105	NM_001145860.2(POP1):c.1297C>T (p.Arg433Trp)	POP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1289269	NM_001145860.2(POP1):c.2057+21A>G	POP1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
POP1	Definitive	Autosomal recessive	anauxetic dysplasia 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POP1	Orphanet:93347	Anauxetic dysplasia

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
POP1	HGNC:30129	ENSG00000104356	Q99575	Ribonucleases P/MRP protein subunit POP1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POP1	Ribonucleases P/MRP protein subunit POP1	Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5’-ends.

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)
POP1	Enzyme (other)	yes	3.1.26.5	Pop1_N, POPLD_dom, Pop1

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
cortical plate	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
POP1	179	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POP1	1,620

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POP1	Q99575	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
tRNA processing in the nucleus	1	196.9×	0.005	POP1

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
tRNA decay	1	3370.4×	9e-04	POP1
tRNA 5’-leader removal	1	1296.3×	0.001	POP1
tRNA processing	1	842.6×	0.001	POP1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
POP1	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
POP1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POP1	3.1.26.5	ribonuclease P

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	POP1
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)
POP1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.