Fanconi renotubular syndrome 5

Summary

Fanconi renotubular syndrome 5 (MONDO:0030056) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi renotubular syndrome 5
Mondo ID	MONDO:0030056
OMIM	618913
DOID	DOID:0080761
UMLS	C5394473
MedGen	1711127
GARD	0016392
Is cancer (heuristic)	no

Also known as: FANCONI RENOTUBULAR SYNDROME 5 · Fanconi renotubular syndrome 5 · Fanconi Renotubular Syndrome, Acadian Variant · FRTS5

Data availability: 11 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Fanconi renotubular syndrome › inherited Fanconi renotubular syndrome › Fanconi renotubular syndrome 5

Related subtypes (2): primary Fanconi syndrome, Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young

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

11 retrieved; paginated sample, class counts are floors:

3 benign, 3 benign/likely benign, 2 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064697	NM_152416.4(NDUFAF6):c.485del (p.Asn162fs)	NDUFAF6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430873	NM_152416.4(NDUFAF6):c.328G>T (p.Gly110Ter)	NDUFAF6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
917900	NM_152416.4(NDUFAF6):c.298-768T>C	NDUFAF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1988700	NM_152416.4(NDUFAF6):c.82G>C (p.Gly28Arg)	LOC113788297	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891813	NM_001354516.2(NDUFAF6):c.38A>G (p.Gln13Arg)	NDUFAF6	Uncertain significance	criteria provided, single submitter
214210	NM_152416.4(NDUFAF6):c.83G>C (p.Gly28Ala)	LOC113788297	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1292552	NM_152416.4(NDUFAF6):c.*16T>C	NDUFAF6	Benign	criteria provided, multiple submitters, no conflicts
136604	NM_152416.4(NDUFAF6):c.663A>G (p.Pro221=)	NDUFAF6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
136605	NM_152416.4(NDUFAF6):c.838G>A (p.Val280Ile)	NDUFAF6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
517080	NM_152416.4(NDUFAF6):c.421-13_421-12del	NDUFAF6	Benign	criteria provided, multiple submitters, no conflicts
559318	NM_152416.4(NDUFAF6):c.420+15dup	NDUFAF6	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
NDUFAF6	Supportive	Autosomal dominant	primary Fanconi syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFAF6	Orphanet:3337	Primary Fanconi renotubular syndrome

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
NDUFAF6	HGNC:28625	ENSG00000156170	Q330K2	NADH dehydrogenase (ubiquinone) complex I, assembly factor 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFAF6	NADH dehydrogenase (ubiquinone) complex I, assembly factor 6	Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NDUFAF6	Other/Unknown	no		Squ/phyt_synthse, Isoprenoid_synthase_dom_sf

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
deltoid	1
right uterine tube	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFAF6	242	ubiquitous	marker	right uterine tube, tibialis anterior, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFAF6	1,990

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NDUFAF6	Q330K2	87.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Complex I biogenesis	1	165.5×	0.015	NDUFAF6
Respiratory electron transport	1	95.2×	0.015	NDUFAF6
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	NDUFAF6
Metabolism	1	11.6×	0.086	NDUFAF6

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
mitochondrial respiratory chain complex I assembly	1	411.0×	0.002	NDUFAF6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
NDUFAF6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	1	NDUFAF6

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)
NDUFAF6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.