Focal segmental glomerulosclerosis 7

Summary

Focal segmental glomerulosclerosis 7 (MONDO:0014451) is a disease caused by PAX2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PAX2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 424

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	focal segmental glomerulosclerosis 7
Mondo ID	MONDO:0014451
OMIM	616002
DOID	DOID:0111132
UMLS	C4014925
MedGen	863362
GARD	0016045
Is cancer (heuristic)	no

Also known as: focal segmental glomerulosclerosis 7 · focal segmental glomerulosclerosis caused by mutation in PAX2 · focal segmental glomerulosclerosis type 7 · FSGS7 · PAX2 focal segmental glomerulosclerosis

Data availability: 424 ClinVar variants · 1 GenCC gene-disease record · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited kidney disorder › inherited focal segmental glomerulosclerosis › focal segmental glomerulosclerosis 7

Related subtypes (7): HIV-associated nephropathy, focal segmental glomerulosclerosis 1, focal segmental glomerulosclerosis 2, focal segmental glomerulosclerosis 5, focal segmental glomerulosclerosis 6, focal segmental glomerulosclerosis 8, focal segmental glomerulosclerosis 9

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

424 retrieved; paginated sample, class counts are floors:

187 uncertain significance, 124 likely benign, 38 pathogenic, 33 likely pathogenic, 18 conflicting classifications of pathogenicity, 12 benign, 7 pathogenic/likely pathogenic, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2424804	NC_000010.10:g.(?102283594)(102510668_?)del	HIF1AN	Pathogenic	criteria provided, single submitter
419700	NM_000278.5(PAX2):c.616+5648T>C	LOC110120845	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066591	NM_000278.5(PAX2):c.418C>T (p.Arg140Trp)	PAX2	Pathogenic	criteria provided, multiple submitters, no conflicts
1072593	NM_000278.5(PAX2):c.250G>A (p.Gly84Ser)	PAX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072594	NM_000278.5(PAX2):c.906C>A (p.Tyr302Ter)	PAX2	Pathogenic	criteria provided, single submitter
1073074	NC_000010.10:g.(?102566167)(102566382_?)del	PAX2	Pathogenic	criteria provided, single submitter
1076561	NM_000278.5(PAX2):c.430C>T (p.Gln144Ter)	PAX2	Pathogenic	criteria provided, single submitter
1179209	GRCh37/hg19 10q24.31(chr10:102568846-102589718)	PAX2	Pathogenic	no assertion criteria provided
1301902	NM_000278.5(PAX2):c.310C>T (p.Arg104Ter)	PAX2	Pathogenic	criteria provided, multiple submitters, no conflicts
1333293	NM_000278.5(PAX2):c.791del (p.Gln264fs)	PAX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1351546	NM_000278.5(PAX2):c.483del (p.Gly162fs)	PAX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13800	NM_000278.5(PAX2):c.221_226dup (p.Glu74_Thr75dup)	PAX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13801	NM_000278.5(PAX2):c.76del (p.Val26fs)	PAX2	Pathogenic	criteria provided, multiple submitters, no conflicts
1419850	NM_000278.5(PAX2):c.785C>A (p.Ser262Ter)	PAX2	Pathogenic	criteria provided, single submitter
155928	NM_000278.5(PAX2):c.565G>A (p.Gly189Arg)	PAX2	Pathogenic	no assertion criteria provided
156294	NM_000278.5(PAX2):c.685C>T (p.Arg229Ter)	PAX2	Pathogenic	criteria provided, multiple submitters, no conflicts
156297	NM_000278.5(PAX2):c.76dup (p.Val26fs)	PAX2	Pathogenic	criteria provided, multiple submitters, no conflicts
1879142	NM_000278.5(PAX2):c.69del (p.Val26fs)	PAX2	Pathogenic	criteria provided, multiple submitters, no conflicts
1938485	NM_000278.5(PAX2):c.750C>A (p.Tyr250Ter)	PAX2	Pathogenic	criteria provided, single submitter
2022166	NM_000278.5(PAX2):c.227dup (p.Ser77fs)	PAX2	Pathogenic	criteria provided, single submitter
2024087	NM_000278.5(PAX2):c.115del (p.Gln39fs)	PAX2	Pathogenic	criteria provided, single submitter
2027274	NM_000278.5(PAX2):c.225del (p.Gly76fs)	PAX2	Pathogenic	criteria provided, single submitter
2032137	NM_000278.5(PAX2):c.97del (p.Leu33fs)	PAX2	Pathogenic	criteria provided, single submitter
2086859	NM_000278.5(PAX2):c.212+1G>T	PAX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2117050	NM_000278.5(PAX2):c.43+1G>A	PAX2	Pathogenic	criteria provided, single submitter
2129979	NM_000278.5(PAX2):c.242del (p.Gly81fs)	PAX2	Pathogenic	criteria provided, single submitter
2152092	NM_000278.5(PAX2):c.792+2T>C	PAX2	Pathogenic	criteria provided, single submitter
2681744	NM_000278.5(PAX2):c.263C>G (p.Pro88Arg)	PAX2	Pathogenic	criteria provided, single submitter
2681750	NM_000278.5(PAX2):c.383_384del (p.Thr128fs)	PAX2	Pathogenic	criteria provided, single submitter
2681762	NM_000278.5(PAX2):c.337G>T (p.Glu113Ter)	PAX2	Pathogenic	criteria provided, single submitter

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
PAX2	Definitive	Autosomal dominant	focal segmental glomerulosclerosis 7	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX2	Orphanet:1475	Renal coloboma syndrome
PAX2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PAX2	Orphanet:97362	Renal hypoplasia, bilateral

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
PAX2	HGNC:8616	ENSG00000075891	Q02962	Paired box protein Pax-2	gencc,clinvar
HIF1AN	HGNC:17113	ENSG00000166135	Q9NWT6	Hypoxia-inducible factor 1-alpha inhibitor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX2	Paired box protein Pax-2	Transcription factor that may have a role in kidney cell differentiation.
HIF1AN	Hypoxia-inducible factor 1-alpha inhibitor	Hydroxylates HIF-1 alpha at ‘Asn-803’ in the C-terminal transactivation domain (CAD).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · 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×	0.228
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAX2	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C
HIF1AN	Enzyme (other)	yes	1.14.11.16	JmjC_dom, RmlC-like_jellyroll, FIH-1_dom_II

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
adult mammalian kidney	1
metanephros cortex	1
renal medulla	1
gastrocnemius	1
muscle of leg	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX2	92	broad	marker	metanephros cortex, renal medulla, adult mammalian kidney
HIF1AN	288	ubiquitous	marker	gastrocnemius, muscle of leg, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX2	2,208
HIF1AN	1,816

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HIF1AN	Q9NWT6	64

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PAX2	Q02962	61.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Formation of intermediate mesoderm	1	713.8×	0.004	PAX2
Cellular response to hypoxia	1	439.2×	0.004	HIF1AN
Nephron development	1	439.2×	0.004	PAX2
Formation of the nephric duct	1	317.2×	0.004	PAX2
Formation of the ureteric bud	1	248.3×	0.004	PAX2

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
optic chiasma development	1	8426.0×	0.001	PAX2
positive regulation of optic nerve formation	1	8426.0×	0.001	PAX2
optic cup morphogenesis involved in camera-type eye development	1	4213.0×	0.001	PAX2
optic nerve structural organization	1	4213.0×	0.001	PAX2
regulation of metanephros size	1	4213.0×	0.001	PAX2
pronephric field specification	1	4213.0×	0.001	PAX2
obsolete negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis	1	4213.0×	0.001	PAX2
obsolete negative regulation of apoptotic process involved in metanephric collecting duct development	1	4213.0×	0.001	PAX2
obsolete negative regulation of apoptotic process involved in metanephric nephron tubule development	1	4213.0×	0.001	PAX2
positive regulation of metanephric DCT cell differentiation	1	4213.0×	0.001	PAX2
nephric duct formation	1	2808.7×	0.002	PAX2
positive regulation of metanephric glomerulus development	1	2808.7×	0.002	PAX2
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	1	2808.7×	0.002	PAX2
ureter maturation	1	2106.5×	0.002	PAX2
metanephric distal convoluted tubule development	1	2106.5×	0.002	PAX2
optic nerve morphogenesis	1	1685.2×	0.002	PAX2
vestibulocochlear nerve formation	1	1685.2×	0.002	PAX2
metanephric mesenchymal cell differentiation	1	1685.2×	0.002	PAX2
metanephric epithelium development	1	1685.2×	0.002	PAX2
metanephric nephron tubule formation	1	1685.2×	0.002	PAX2
regulation of metanephric nephron tubule epithelial cell differentiation	1	1685.2×	0.002	PAX2
regulation of vascular endothelial growth factor receptor signaling pathway	1	1404.3×	0.002	HIF1AN
positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	1404.3×	0.002	PAX2
ureter development	1	1404.3×	0.002	PAX2
pronephros development	1	1203.7×	0.002	PAX2
metanephric mesenchyme development	1	1203.7×	0.002	PAX2
mesenchymal to epithelial transition involved in metanephros morphogenesis	1	1053.2×	0.002	PAX2
mesodermal cell fate specification	1	1053.2×	0.002	PAX2
retinal pigment epithelium development	1	842.6×	0.002	PAX2
metanephric collecting duct development	1	842.6×	0.002	PAX2

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HIF1AN	DAPRODUSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HIF1AN	4	4
PAX2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DAPRODUSTAT	4	HIF1AN
VADADUSTAT	4	HIF1AN
QUERCETIN	3	HIF1AN
MOLIDUSTAT	2	HIF1AN

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HIF1AN	20	Binding:20
PAX2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HIF1AN	1.14.11.16, 1.14.11.30	peptide-aspartate beta-dioxygenase, hypoxia-inducible factor-asparagine dioxygenase

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

4 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.

Compound	Max phase	Cohort target (bioactivity)
DAPRODUSTAT	4	HIF1AN
VADADUSTAT	4	HIF1AN
QUERCETIN	3	HIF1AN
MOLIDUSTAT	2	HIF1AN

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HIF1AN
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	PAX2

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)
PAX2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.