Focal segmental glomerulosclerosis 8

Summary

Focal segmental glomerulosclerosis 8 (MONDO:0014462) is a disease caused by ANLN (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ANLN (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 63

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	focal segmental glomerulosclerosis 8
Mondo ID	MONDO:0014462
OMIM	616032
DOID	DOID:0111133
UMLS	C4014993
MedGen	863430
GARD	0016051
Is cancer (heuristic)	no

Also known as: ANLN focal segmental glomerulosclerosis · focal segmental glomerulosclerosis 8 · focal segmental glomerulosclerosis caused by mutation in ANLN · focal segmental glomerulosclerosis type 8 · FSGS8

Data availability: 63 ClinVar variants · 3 GenCC gene-disease records.

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 8

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 7, 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

63 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 20 benign, 7 benign/likely benign, 5 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
156221	NM_018685.5(ANLN):c.1291C>T (p.Arg431Cys)	ANLN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
156222	NM_018685.5(ANLN):c.1852G>T (p.Gly618Cys)	ANLN	Pathogenic	criteria provided, single submitter
1424262	NM_018685.5(ANLN):c.2056C>T (p.Arg686Cys)	ANLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2439105	NM_018685.5(ANLN):c.1547A>T (p.Lys516Ile)	ANLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3127052	NM_018685.5(ANLN):c.1216G>C (p.Ala406Pro)	ANLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
693991	NM_018685.5(ANLN):c.2385T>A (p.Ser795Arg)	ANLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
972322	NM_018685.5(ANLN):c.752G>A (p.Ser251Asn)	ANLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1026642	NM_018685.5(ANLN):c.2440A>G (p.Lys814Glu)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029710	NM_018685.5(ANLN):c.1979A>G (p.Asp660Gly)	ANLN	Uncertain significance	criteria provided, single submitter
1077038	NM_018685.5(ANLN):c.1588A>C (p.Lys530Gln)	ANLN	Uncertain significance	criteria provided, single submitter
1339108	NM_018685.5(ANLN):c.65A>G (p.Lys22Arg)	ANLN	Uncertain significance	criteria provided, single submitter
1440732	NM_018685.5(ANLN):c.1198A>G (p.Ile400Val)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1522565	NM_018685.5(ANLN):c.3062A>T (p.Asp1021Val)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1524609	NM_018685.5(ANLN):c.1127G>A (p.Arg376His)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805287	NM_018685.5(ANLN):c.3158G>A (p.Arg1053His)	ANLN	Uncertain significance	criteria provided, single submitter
1964058	NM_018685.5(ANLN):c.437T>C (p.Met146Thr)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439106	NM_018685.5(ANLN):c.896C>A (p.Ser299Tyr)	ANLN	Uncertain significance	criteria provided, single submitter
2442158	NM_018685.5(ANLN):c.3035A>T (p.Asn1012Ile)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2585263	NM_018685.5(ANLN):c.28G>A (p.Glu10Lys)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
266013	NM_018685.5(ANLN):c.1138C>T (p.Arg380Cys)	ANLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
3068300	NM_018685.5(ANLN):c.3010C>T (p.Arg1004Ter)	ANLN	Uncertain significance	criteria provided, single submitter
3392548	NM_018685.5(ANLN):c.1963C>T (p.Arg655Ter)	ANLN	Uncertain significance	criteria provided, single submitter
3779516	NM_018685.5(ANLN):c.1685C>T (p.Ser562Leu)	ANLN	Uncertain significance	criteria provided, single submitter
3779517	NM_018685.5(ANLN):c.2938G>T (p.Val980Leu)	ANLN	Uncertain significance	criteria provided, single submitter
3779518	NM_018685.5(ANLN):c.3G>A (p.Met1Ile)	ANLN	Uncertain significance	criteria provided, single submitter
3895503	NM_018685.5(ANLN):c.2824G>A (p.Val942Ile)	ANLN	Uncertain significance	criteria provided, single submitter
4292296	NM_018685.5(ANLN):c.1130T>C (p.Phe377Ser)	ANLN	Uncertain significance	criteria provided, single submitter
4526543	NM_018685.5(ANLN):c.1395+2T>A	ANLN	Uncertain significance	criteria provided, single submitter
4532068	NM_018685.5(ANLN):c.1309T>C (p.Cys437Arg)	ANLN	Uncertain significance	criteria provided, single submitter
4540441	NM_018685.5(ANLN):c.3271A>G (p.Thr1091Ala)	ANLN	Uncertain significance	criteria provided, single submitter

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
ANLN	Strong	Autosomal dominant	focal segmental glomerulosclerosis 8	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANLN	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome

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
ANLN	HGNC:14082	ENSG00000011426	Q9NQW6	Anillin	gencc,clinvar
SYNPO	HGNC:30672	ENSG00000171992	Q8N3V7	Synaptopodin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANLN	Anillin	Required for cytokinesis.
SYNPO	Synaptopodin	Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANLN	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, AHD
SYNPO	Other/Unknown	no		Synaptopodin_domain

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
C1 segment of cervical spinal cord	1
corpus callosum	1
inferior vagus X ganglion	1
apex of heart	1
descending thoracic aorta	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANLN	222	ubiquitous	marker	corpus callosum, inferior vagus X ganglion, C1 segment of cervical spinal cord
SYNPO	291	ubiquitous	marker	hindlimb stylopod muscle, apex of heart, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANLN	6,413
SYNPO	2,704

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANLN	Q9NQW6	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SYNPO	Q8N3V7	50.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 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
RHOB GTPase cycle	1	154.3×	0.024	ANLN
RHOC GTPase cycle	1	146.4×	0.024	ANLN
RHOA GTPase cycle	1	74.6×	0.029	ANLN
RHO GTPase cycle	1	60.1×	0.029	ANLN
Signaling by Rho GTPases	1	34.2×	0.035	ANLN
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.035	ANLN
Signal Transduction	1	10.2×	0.098	ANLN

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
septin ring assembly	1	8426.0×	7e-04	ANLN
spine apparatus assembly	1	8426.0×	7e-04	SYNPO
septin ring organization	1	4213.0×	7e-04	ANLN
positive regulation of bleb assembly	1	4213.0×	7e-04	ANLN
actomyosin contractile ring assembly	1	2106.5×	0.001	ANLN
podocyte cell migration	1	1203.7×	0.002	ANLN
regulation of exit from mitosis	1	601.9×	0.002	ANLN
positive regulation of actin filament bundle assembly	1	601.9×	0.002	SYNPO
regulation of stress fiber assembly	1	495.6×	0.002	SYNPO
mitotic cytokinesis	1	129.6×	0.008	ANLN
hematopoietic progenitor cell differentiation	1	118.7×	0.008	ANLN

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
ANLN	0	0
SYNPO	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	ANLN, SYNPO

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)
ANLN	0	—
SYNPO	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.