Familial steroid-resistant nephrotic syndrome with sensorineural deafness

Summary

Familial steroid-resistant nephrotic syndrome with sensorineural deafness (MONDO:0013836) is a disease caused by COQ6 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: COQ6 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 109

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial steroid-resistant nephrotic syndrome with sensorineural deafness
Mondo ID	MONDO:0013836
OMIM	614650
Orphanet	280406
DOID	DOID:0070243
UMLS	C3553349
MedGen	766263
GARD	0017295
Is cancer (heuristic)	no

Also known as: coenzyme Q10 deficiency, primary, 6 · coenzyme Q10 deficiency, primary, type 6 · COQ10D6

Data availability: 109 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › coenzyme Q10 deficiency › familial steroid-resistant nephrotic syndrome with sensorineural deafness

Related subtypes (8): coenzyme Q10 deficiency, primary, 1, autosomal recessive ataxia due to ubiquinone deficiency, deafness-encephaloneuropathy-obesity-valvulopathy syndrome, coenzyme Q10 deficiency, primary, 3, encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome, neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome, primary coenzyme Q10 deficiency 8, coenzyme q10 deficiency, primary, 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

109 retrieved; paginated sample, class counts are floors:

72 uncertain significance, 11 pathogenic, 8 likely pathogenic, 7 conflicting classifications of pathogenicity, 5 benign, 3 pathogenic/likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1679762	NM_182476.3(COQ6):c.349C>T (p.Arg117Ter)	COQ6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2977155	NM_182476.3(COQ6):c.248dup (p.Tyr83Ter)	COQ6	Pathogenic	criteria provided, multiple submitters, no conflicts
31595	NM_182476.3(COQ6):c.1058C>A (p.Ala353Asp)	COQ6	Pathogenic	criteria provided, single submitter
31598	NM_182476.3(COQ6):c.484C>T (p.Arg162Ter)	COQ6	Pathogenic	no assertion criteria provided
375341	NM_182476.3(COQ6):c.564G>A (p.Trp188Ter)	COQ6	Pathogenic	criteria provided, single submitter
375344	NM_182476.3(COQ6):c.1341G>A (p.Trp447Ter)	COQ6	Pathogenic	no assertion criteria provided
423078	NM_182476.3(COQ6):c.1153_1154del (p.Asp385fs)	COQ6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
434818	NM_182476.3(COQ6):c.1069del (p.Val357fs)	COQ6	Pathogenic	criteria provided, single submitter
807582	NM_182476.3(COQ6):c.782C>T (p.Pro261Leu)	COQ6	Pathogenic	criteria provided, multiple submitters, no conflicts
807584	NM_182476.3(COQ6):c.1237G>T (p.Glu413Ter)	COQ6	Pathogenic	criteria provided, single submitter
992499	NM_182476.3(COQ6):c.189_191del (p.Lys64del)	COQ6	Pathogenic	criteria provided, multiple submitters, no conflicts
1322156	NM_182476.3(COQ6):c.788_789del (p.Leu262_Ser263insTer)	ENTPD5	Pathogenic	criteria provided, single submitter
1324160	NM_182476.3(COQ6):c.1027C>T (p.Arg343Ter)	ENTPD5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375342	NM_182476.3(COQ6):c.763G>A (p.Gly255Arg)	ENTPD5	Pathogenic	no assertion criteria provided
3576687	NM_182476.3(COQ6):c.22_44dup (p.Pro16fs)	COQ6	Likely pathogenic	criteria provided, single submitter
3576700	NM_182476.3(COQ6):c.352del (p.Met118fs)	COQ6	Likely pathogenic	criteria provided, single submitter
3576712	NM_182476.3(COQ6):c.613-8_614del	COQ6	Likely pathogenic	criteria provided, single submitter
3576721	NM_182476.3(COQ6):c.988C>T (p.Gln330Ter)	COQ6	Likely pathogenic	criteria provided, single submitter
3767190	NM_182476.3(COQ6):c.10C>T (p.Arg4Trp)	COQ6	Likely pathogenic	criteria provided, single submitter
4277511	NM_182476.3(COQ6):c.974del (p.Lys325fs)	COQ6	Likely pathogenic	criteria provided, single submitter
4845886	NM_182476.3(COQ6):c.685C>T (p.Gln229Ter)	COQ6	Likely pathogenic	criteria provided, single submitter
807583	NM_182476.3(COQ6):c.1079G>T (p.Arg360Leu)	COQ6	Likely pathogenic	criteria provided, single submitter
1416161	NM_182476.3(COQ6):c.346C>T (p.Arg116Trp)	COQ6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1693622	NM_182476.3(COQ6):c.877G>A (p.Val293Ile)	COQ6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2602219	NM_182476.3(COQ6):c.1065G>A (p.Glu355=)	COQ6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1370573	NM_182476.3(COQ6):c.1078C>T (p.Arg360Trp)	ENTPD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2963583	NM_182476.3(COQ6):c.610T>C (p.Leu204=)	ENTPD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2992442	NM_182476.3(COQ6):c.549C>T (p.Ala183=)	ENTPD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
512412	NM_182476.3(COQ6):c.498C>T (p.Leu166=)	ENTPD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1303239	NM_182476.3(COQ6):c.157G>A (p.Ala53Thr)	COQ6	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
COQ6	Strong	Autosomal recessive	familial steroid-resistant nephrotic syndrome with sensorineural deafness	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COQ6	Orphanet:280406	Familial steroid-resistant nephrotic syndrome with sensorineural deafness
COQ6	Orphanet:93921	Full schwannomatosis

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
COQ6	HGNC:20233	ENSG00000119723	Q9Y2Z9	Ubiquinone biosynthesis monooxygenase COQ6, mitochondrial	gencc,clinvar
ENTPD5	HGNC:3367	ENSG00000187097	O75356	Nucleoside diphosphate phosphatase ENTPD5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ6	Ubiquinone biosynthesis monooxygenase COQ6, mitochondrial	FAD-dependent monooxygenase required for two non-consecutive steps during ubiquinone biosynthesis.
ENTPD5	Nucleoside diphosphate phosphatase ENTPD5	Hydrolyzes nucleoside diphosphates with a preference for GDP, IDP and UDP compared to ADP and CDP.

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)
COQ6	Other/Unknown	no		UbQ_mOase_COQ6, FAD-bd, UbiH/COQ6
ENTPD5	Other/Unknown	no		GDA1_CD39_NTPase

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
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1
colonic mucosa	1
mucosa of sigmoid colon	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ6	209	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
ENTPD5	257	ubiquitous	marker	mucosa of sigmoid colon, colonic mucosa, rectum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COQ6	3,105
ENTPD5	825

Intra-cohort edges

A	B	Sources
COQ6	ENTPD5	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ENTPD5	O75356	87.55
COQ6	Q9Y2Z9	84.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Phosphate bond hydrolysis by NTPDase proteins	1	713.8×	0.003	ENTPD5
Ubiquinol biosynthesis	1	439.2×	0.003	COQ6
Purinergic signaling in leishmaniasis infection	1	211.5×	0.005	ENTPD5

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
UDP-alpha-D-glucose metabolic process	1	2808.7×	8e-04	ENTPD5
UDP catabolic process	1	2808.7×	8e-04	ENTPD5
‘de novo’ post-translational protein folding	1	2106.5×	8e-04	ENTPD5
ubiquinone biosynthetic process	1	468.1×	0.003	COQ6
protein N-linked glycosylation	1	131.7×	0.008	ENTPD5

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COQ6	0	0
ENTPD5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ENTPD5	4	Binding:4

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	COQ6, ENTPD5

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)
COQ6	0	—
ENTPD5	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.