Fanconi renotubular syndrome 3

disease
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Also known as EHHADH Fanconi syndromeFanconi renotubular syndrome type 3Fanconi syndrome caused by mutation in EHHADHFRTS3

Summary

Fanconi renotubular syndrome 3 (MONDO:0014275) is a disease caused by EHHADH (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

  • Causal gene: EHHADH (GenCC Strong)
  • Cohort genes: 1
  • ClinVar variants: 18
  • Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameFanconi renotubular syndrome 3
Mondo IDMONDO:0014275
OMIM615605
DOIDDOID:0080759
UMLSC3810100
MedGen816430
GARD0015991
Is cancer (heuristic)no

Also known as: EHHADH Fanconi syndrome · Fanconi renotubular syndrome 3 · Fanconi renotubular syndrome type 3 · Fanconi syndrome caused by mutation in EHHADH · FRTS3

Data availability: 18 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic diseaseFanconi renotubular syndrome › inherited Fanconi renotubular syndrome › primary Fanconi syndromeFanconi renotubular syndrome 3

Related subtypes (2): Fanconi renotubular syndrome 2, Fanconi renotubular syndrome 1

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

18 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 3 conflicting classifications of pathogenicity, 1 no classifications from unflagged records, 1 likely benign

ClinVarVariant (HGVS)GeneClassificationReview
500959NM_001966.4(EHHADH):c.302G>A (p.Gly101Glu)EHHADHConflicting classifications of pathogenicitycriteria provided, conflicting classifications
595172NM_001966.4(EHHADH):c.673C>G (p.Pro225Ala)EHHADHConflicting classifications of pathogenicitycriteria provided, conflicting classifications
598561NM_001966.4(EHHADH):c.117del (p.Ala39_Val40insTer)EHHADHConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1331703NM_001966.4(EHHADH):c.734A>G (p.Tyr245Cys)EHHADHUncertain significancecriteria provided, single submitter
2431818NM_001966.4(EHHADH):c.42C>G (p.Ile14Met)EHHADHUncertain significancecriteria provided, single submitter
2441192NM_001966.4(EHHADH):c.2011G>T (p.Gly671Trp)EHHADHUncertain significancecriteria provided, single submitter
2628688NM_001966.4(EHHADH):c.126C>A (p.Asp42Glu)EHHADHUncertain significancecriteria provided, multiple submitters, no conflicts
3044426NM_001966.4(EHHADH):c.1651C>T (p.Arg551Ter)EHHADHUncertain significancecriteria provided, single submitter
3064451NM_001966.4(EHHADH):c.1984G>A (p.Gly662Arg)EHHADHUncertain significancecriteria provided, single submitter
3589065NM_001966.4(EHHADH):c.1015A>T (p.Met339Leu)EHHADHUncertain significancecriteria provided, single submitter
3776154NM_001966.4(EHHADH):c.1397T>G (p.Ile466Ser)EHHADHUncertain significancecriteria provided, single submitter
4277529NM_001966.4(EHHADH):c.688C>T (p.Gln230Ter)EHHADHUncertain significancecriteria provided, single submitter
4278072NM_001966.4(EHHADH):c.1897C>A (p.Arg633Ser)EHHADHUncertain significancecriteria provided, single submitter
4279903NM_001966.4(EHHADH):c.1460C>T (p.Pro487Leu)EHHADHUncertain significancecriteria provided, single submitter
4279904NM_001966.4(EHHADH):c.1865G>A (p.Arg622His)EHHADHUncertain significancecriteria provided, single submitter
595249NM_001966.4(EHHADH):c.1093T>G (p.Leu365Val)EHHADHUncertain significancecriteria provided, multiple submitters, no conflicts
96711NM_001966.4(EHHADH):c.7G>A (p.Glu3Lys)EHHADHno classifications from unflagged recordsno classifications from unflagged records
977889NM_001966.4(EHHADH):c.1189dup (p.Ser397fs)EHHADHLikely benignno assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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.

GeneClassificationInheritanceDiseaseRecords
EHHADHStrongAutosomal dominantFanconi renotubular syndrome 34

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
EHHADHOrphanet:300Bifunctional enzyme deficiency
EHHADHOrphanet:3337Primary Fanconi renotubular syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
EHHADHHGNC:3247ENSG00000113790Q08426Peroxisomal bifunctional enzymegencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
EHHADHPeroxisomal bifunctional enzymePeroxisomal trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities.

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.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
EHHADHOther/UnknownnoEnoyl-CoA_hydra/iso, 3HC_DH_C, 3-OHacyl-CoA_DH_NAD-bd

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
liver1
nephron tubule1
right lobe of liver1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
EHHADH241ubiquitousmarkerright lobe of liver, liver, nephron tubule

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
EHHADH3,281

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
EHHADHQ0842695.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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.

PathwayCohort genesFoldFDRSample cohort genes
Beta-oxidation of very long chain fatty acids1878.5×0.002EHHADH
Peroxisomal protein import1173.0×0.006EHHADH

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 termCohort genesFoldFDRSample cohort genes
fatty acid derivative biosynthetic process11532.0×0.002EHHADH
fatty acid beta-oxidation using acyl-CoA oxidase11123.5×0.002EHHADH
alpha-linolenic acid metabolic process1887.0×0.002EHHADH
unsaturated fatty acid biosynthetic process1648.1×0.002EHHADH
long-chain fatty acid biosynthetic process1443.5×0.003EHHADH
fatty acid beta-oxidation1374.5×0.003EHHADH

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

SymbolMoleculesMax phase
EHHADH00

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):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1EHHADH

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
EHHADH0

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06065852Not specifiedRECRUITINGNational Registry of Rare Kidney Diseases