Podoconiosis

Summary

Podoconiosis (MONDO:0005425) is a disease with 2 cohort genes (3 GWAS associations across 2 studies) and 4 clinical trials.

At a glance

• Cohort genes: 2
• GWAS associations: 3
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	podoconiosis
Mondo ID	MONDO:0005425
EFO	EFO:0004712
DOID	DOID:0050138
SNOMED CT	47595008
UMLS	C1280469
MedGen	473377
Is cancer (heuristic)	no

Also known as: elephantiasis from soil · non-filarial elephantiasis · nonfilarial elephantiasis · soil elephantiasis

Data availability: 3 GWAS associations (2 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › lymphoid system disorder › lymphatic system disorder › lymphedema › elephantiasis › podoconiosis

Related subtypes (1): filarial elephantiasis

Genetics & variants

GWAS landscape

3 GWAS associations across 2 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9270911	2e-12	HLA-DRB1 - HLA-DQA1	T
rs9268831	2e-09	HLA-DRB9	T
rs73732611	5e-09	MTCO3P1 - HLA-DQB3	C

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011363	Gebresilase T	2021	1,137	1,152	Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups.
GCST001464	Tekola Ayele F	2012	194	0	HLA class II locus and susceptibility to podoconiosis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
regulatory_region_variant	1
non_coding_transcript_exon_variant	1
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9270911	6	32604425	C>T	0.44	regulatory_region_variant	HLA-DRB1 - HLA-DQA1	2e-12	Tier 3: regulatory
rs9268831	6	32459971	C>A,T	0.46	non_coding_transcript_exon_variant	HLA-DRB9	2e-09	Tier 4: intronic/intergenic
rs73732611	6	32727298	T>C	0.07	intergenic_variant	MTCO3P1 - HLA-DQB3	5e-09	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

2 cohort genes, 0 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HLA-DQB3	HGNC:4946	ENSG00000226030		major histocompatibility complex, class II, DQ beta 3	gwas
HLA-DRB9	HGNC:4957	ENSG00000196301		major histocompatibility complex, class II, DR beta 9 (pseudogene)	gwas

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HLA-DQB3	Other/Unknown	no
HLA-DRB9	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
cortical plate	1
ventricular zone	1
granulocyte	1
leukocyte	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HLA-DQB3	4		yes	colonic epithelium, ventricular zone, cortical plate
HLA-DRB9	106		yes	primordial germ cell in gonad, granulocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HLA-DQB3	0
HLA-DRB9	0

Structural data

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

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
HLA-DQB3	0	0
HLA-DRB9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	HLA-DQB3, HLA-DRB9

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)
HLA-DQB3	0	—
HLA-DRB9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02839772	PHASE3	COMPLETED	An RCT to Evaluate the Effect of a New Skin Care Regimen on SBF in Those With Podoconiosis
NCT07506967	Not specified	NOT_YET_RECRUITING	Early Detection and AI-Based Management of Skin-Related Neglected Tropical Diseases in Sub-Saharan Africa by Frontline Health Workers
NCT01160523	Not specified	COMPLETED	Promoting Consistent Shoe Use Among Children At High Risk for Podoconiosis
NCT01939431	Not specified	TERMINATED	Genetic and Other Aspects of Podoconiosis