Nephrotic syndrome, type 9

Summary

Nephrotic syndrome, type 9 (MONDO:0014257) is a disease caused by COQ8B (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COQ8B (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 51

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 9
Mondo ID	MONDO:0014257
OMIM	615573
DOID	DOID:0080391
UMLS	C3809965
MedGen	816295
GARD	0015989
Is cancer (heuristic)	no

Also known as: COQ8B nephrotic syndrome · nephrotic syndrome caused by mutation in COQ8B · nephrotic syndrome, type 9 · NPHS9

Data availability: 51 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › familial idiopathic steroid-resistant nephrotic syndrome › nephrotic syndrome, type 9

Related subtypes (13): nephrotic syndrome, type 2, focal segmental glomerulosclerosis 1, nephrotic syndrome, type 3, nephrotic syndrome, type 6, familial steroid-resistant nephrotic syndrome with sensorineural deafness, nephrotic syndrome, type 8, nephrotic syndrome, type 10, nephrotic syndrome, type 11, nephrotic syndrome, type 12, nephrotic syndrome, type 13, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation, familial idiopathic steroid-resistant nephrotic syndrome with minimal changes, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis

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

51 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 10 conflicting classifications of pathogenicity, 8 pathogenic/likely pathogenic, 8 pathogenic, 6 likely pathogenic, 3 benign/likely benign, 2 not provided, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1077023	NM_024876.4(COQ8B):c.893+2T>A	COQ8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1708373	NM_024876.4(COQ8B):c.1339dup (p.Glu447fs)	COQ8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2082603	NM_024876.4(COQ8B):c.1084C>T (p.Arg362Ter)	COQ8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681741	NM_024876.4(COQ8B):c.1297-2A>G	COQ8B	Pathogenic	criteria provided, single submitter
2681743	NM_024876.4(COQ8B):c.33del (p.Thr12fs)	COQ8B	Pathogenic	criteria provided, single submitter
3064005	NM_024876.4(COQ8B):c.367+1G>A	COQ8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375336	NM_024876.4(COQ8B):c.645del (p.Phe215fs)	COQ8B	Pathogenic	criteria provided, multiple submitters, no conflicts
375337	NM_024876.4(COQ8B):c.1430G>A (p.Arg477Gln)	COQ8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
91845	NM_024876.4(COQ8B):c.532C>T (p.Arg178Trp)	COQ8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
91846	NM_024876.4(COQ8B):c.857A>G (p.Asp286Gly)	COQ8B	Pathogenic	no assertion criteria provided
91847	NM_024876.4(COQ8B):c.1447G>T (p.Glu483Ter)	COQ8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
91848	NM_024876.4(COQ8B):c.958C>T (p.Arg320Trp)	COQ8B	Pathogenic	no assertion criteria provided
91849	NM_024876.4(COQ8B):c.1027C>T (p.Arg343Trp)	COQ8B	Pathogenic	no assertion criteria provided
91851	NM_024876.4(COQ8B):c.1356_1362del (p.Gln452fs)	COQ8B	Pathogenic/Likely pathogenic	no assertion criteria provided
974475	NM_024876.4(COQ8B):c.1035+2T>C	COQ8B	Pathogenic	criteria provided, multiple submitters, no conflicts
988900	NM_024876.4(COQ8B):c.748G>A (p.Asp250Asn)	COQ8B	Pathogenic	no assertion criteria provided
2444313	NM_024876.4(COQ8B):c.271C>T (p.Arg91Cys)	COQ8B	Likely pathogenic	criteria provided, single submitter
2736895	NM_024876.4(COQ8B):c.759C>A (p.Asn253Lys)	COQ8B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4293095	NM_024876.4(COQ8B):c.449G>A (p.Arg150Gln)	COQ8B	Likely pathogenic	criteria provided, single submitter
4845808	NM_024876.4(COQ8B):c.49_58del (p.Gly17fs)	COQ8B	Likely pathogenic	criteria provided, single submitter
91850	NM_024876.4(COQ8B):c.1199dup (p.His400fs)	COQ8B	Likely pathogenic	criteria provided, single submitter
974476	NM_024876.4(COQ8B):c.439T>C (p.Cys147Arg)	COQ8B	Likely pathogenic	criteria provided, single submitter
1077024	NM_024876.4(COQ8B):c.1035+3A>G	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1559379	NM_024876.4(COQ8B):c.796G>A (p.Ala266Thr)	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1565408	NM_024876.4(COQ8B):c.826G>C (p.Ala276Pro)	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2681740	NM_024876.4(COQ8B):c.1468C>T (p.Arg490Cys)	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3377728	NM_024876.4(COQ8B):c.116G>T (p.Gly39Val)	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3778092	NM_024876.4(COQ8B):c.1493C>A (p.Ala498Asp)	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
521659	NM_024876.4(COQ8B):c.1560G>A (p.Trp520Ter)	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
708472	NM_024876.4(COQ8B):c.1297-6T>G	COQ8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
COQ8B	Definitive	Autosomal recessive	nephrotic syndrome, type 9	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COQ8B	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
COQ8B	Orphanet:791	Retinitis pigmentosa

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
COQ8B	HGNC:19041	ENSG00000123815	Q96D53	Atypical kinase COQ8B, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ8B	Atypical kinase COQ8B, mitochondrial	Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COQ8B	Kinase	yes		ABC1_dom, Kinase-like_dom_sf, ADCK3_dom

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
adenohypophysis	1
pituitary gland	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ8B	227	ubiquitous	marker	right uterine tube, adenohypophysis, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COQ8B	1,111

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COQ8B	Q96D53	77.00

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
Ubiquinol biosynthesis	1	878.5×	0.001	COQ8B

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
cerebellar Purkinje cell layer morphogenesis	1	8426.0×	2e-04	COQ8B
ubiquinone biosynthetic process	1	936.2×	0.001	COQ8B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
COQ8B	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COQ8B	9	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	COQ8B
VANDETANIB	4	COQ8B
ERLOTINIB	4	COQ8B
CRIZOTINIB	4	COQ8B
CANERTINIB	3	COQ8B
TG100-115	2	COQ8B
R-406	2	COQ8B
PELITINIB	2	COQ8B
BMS-387032	1	COQ8B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
COQ8B	77	Binding:77

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

9 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)
FEDRATINIB	4	COQ8B
VANDETANIB	4	COQ8B
ERLOTINIB	4	COQ8B
CRIZOTINIB	4	COQ8B
CANERTINIB	3	COQ8B
TG100-115	2	COQ8B
R-406	2	COQ8B
PELITINIB	2	COQ8B
BMS-387032	1	COQ8B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	COQ8B
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.