Focal segmental glomerulosclerosis 6

Summary

Focal segmental glomerulosclerosis 6 (MONDO:0013589) is a disease caused by MYO1E (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MYO1E (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 212

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	focal segmental glomerulosclerosis 6
Mondo ID	MONDO:0013589
OMIM	614131
DOID	DOID:0111131
UMLS	C3279905
MedGen	481535
GARD	0015761
Is cancer (heuristic)	no

Also known as: focal segmental glomerulosclerosis 6 · focal segmental glomerulosclerosis caused by mutation in MYO1E · focal segmental glomerulosclerosis type 6 · FSGS6 · MYO1E focal segmental glomerulosclerosis

Data availability: 212 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 6

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

212 retrieved; paginated sample, class counts are floors:

150 uncertain significance, 16 likely benign, 14 conflicting classifications of pathogenicity, 13 benign/likely benign, 10 likely pathogenic, 5 pathogenic, 3 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179070	NM_004998.4(MYO1E):c.979C>T (p.Gln327Ter)	MYO1E	Pathogenic	criteria provided, single submitter
2500430	NM_004998.4(MYO1E):c.141C>G (p.Tyr47Ter)	MYO1E	Pathogenic	criteria provided, multiple submitters, no conflicts
30191	NM_004998.4(MYO1E):c.475G>C (p.Ala159Pro)	MYO1E	Pathogenic	no assertion criteria provided
30192	NM_004998.4(MYO1E):c.2085T>G (p.Tyr695Ter)	MYO1E	Pathogenic	no assertion criteria provided
3577584	NM_004998.4(MYO1E):c.310_313del (p.Glu104fs)	MYO1E	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
974435	NM_004998.4(MYO1E):c.2908C>T (p.Gln970Ter)	MYO1E	Pathogenic	criteria provided, single submitter
3577505	NM_004998.4(MYO1E):c.2879del	MYO1E	Likely pathogenic	criteria provided, single submitter
3577514	NM_004998.4(MYO1E):c.2692C>T (p.Gln898Ter)	MYO1E	Likely pathogenic	criteria provided, single submitter
3577532	NM_004998.4(MYO1E):c.2145C>G (p.Tyr715Ter)	MYO1E	Likely pathogenic	criteria provided, single submitter
3577545	NM_004998.4(MYO1E):c.1663A>T (p.Lys555Ter)	MYO1E	Likely pathogenic	criteria provided, single submitter
3577547	NM_004998.4(MYO1E):c.1631_1634del (p.Ser544fs)	MYO1E	Likely pathogenic	criteria provided, single submitter
3577552	NM_004998.4(MYO1E):c.1506del (p.Phe502fs)	MYO1E	Likely pathogenic	criteria provided, single submitter
3577554	NM_004998.4(MYO1E):c.1462C>T (p.Gln488Ter)	MYO1E	Likely pathogenic	criteria provided, single submitter
3577556	NM_004998.4(MYO1E):c.1423G>T (p.Glu475Ter)	MYO1E	Likely pathogenic	criteria provided, single submitter
3577572	NM_004998.4(MYO1E):c.808G>T (p.Glu270Ter)	MYO1E	Likely pathogenic	criteria provided, single submitter
807636	NM_004998.4(MYO1E):c.2060T>C (p.Leu687Ser)	MYO1E	Likely pathogenic	criteria provided, single submitter
1006073	NM_004998.4(MYO1E):c.2678G>A (p.Gly893Asp)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1154662	NM_004998.4(MYO1E):c.910+4C>T	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1404370	NM_004998.4(MYO1E):c.2459G>A (p.Arg820Gln)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1667344	NM_004998.4(MYO1E):c.189G>A (p.Lys63=)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1911850	NM_004998.4(MYO1E):c.2625T>C (p.Asn875=)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2443182	NM_004998.4(MYO1E):c.1257G>C (p.Leu419=)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2759822	NM_004998.4(MYO1E):c.2383G>A (p.Gly795Arg)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3042804	NM_004998.4(MYO1E):c.976C>T (p.Arg326Trp)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3048782	NM_004998.4(MYO1E):c.1416G>A (p.Ala472=)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3577494	NM_004998.4(MYO1E):c.3251-6C>G	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3577560	NM_004998.4(MYO1E):c.1255C>T (p.Leu419=)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
871066	NM_004998.4(MYO1E):c.2627C>G (p.Thr876Arg)	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
974434	NM_004998.4(MYO1E):c.2481-12A>G	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
983002	NM_004998.4(MYO1E):c.332+8G>A	MYO1E	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
MYO1E	Strong	Autosomal recessive	focal segmental glomerulosclerosis 6	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO1E	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
MYO1E	HGNC:7599	ENSG00000157483	Q12965	Unconventional myosin-Ie	gencc,clinvar
LDHAL6B	HGNC:21481	ENSG00000171989	Q9BYZ2	L-lactate dehydrogenase A-like 6B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO1E	Unconventional myosin-Ie	Actin-based motor molecule with ATPase activity.

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)
MYO1E	Scaffold/PPI	no		SH3_domain, Myosin_head_motor_dom-like, Myosin_TH1
LDHAL6B	Other/Unknown	no		Lactate/malate_DH_N, L-lactate/malate_DH, L-lactate_DH

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
gall bladder	1
sural nerve	1
adult organism	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO1E	235	ubiquitous	marker	calcaneal tendon, sural nerve, gall bladder
LDHAL6B	93	tissue_specific	yes	right testis, adult organism, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LDHAL6B	3,162
MYO1E	2,040

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LDHAL6B	Q9BYZ2	88.68
MYO1E	Q12965	80.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Pyruvate metabolism	1	407.9×	0.007	LDHAL6B
Aerobic respiration and respiratory electron transport	1	88.5×	0.017	LDHAL6B
Metabolism	1	11.6×	0.086	LDHAL6B

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
pyruvate fermentation to lactate	1	4213.0×	0.003	LDHAL6B
post-embryonic hemopoiesis	1	1404.3×	0.003	MYO1E
pyruvate catabolic process	1	1053.2×	0.003	LDHAL6B
lactate metabolic process	1	936.2×	0.003	LDHAL6B
glomerular basement membrane development	1	766.0×	0.003	MYO1E
podocyte development	1	766.0×	0.003	MYO1E
glomerulus development	1	648.1×	0.003	MYO1E
glomerular filtration	1	468.1×	0.003	MYO1E
platelet-derived growth factor receptor signaling pathway	1	280.9×	0.005	MYO1E
vasculogenesis	1	127.7×	0.010	MYO1E
actin filament organization	1	59.3×	0.020	MYO1E
endocytosis	1	47.6×	0.023	MYO1E
in utero embryonic development	1	36.0×	0.028	MYO1E

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
MYO1E	0	0
LDHAL6B	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	MYO1E, LDHAL6B

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)
MYO1E	0	—
LDHAL6B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.