Fanconi renotubular syndrome 1

Summary

Fanconi renotubular syndrome 1 (MONDO:0024525) is a disease caused by GATM (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Causal gene: GATM (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 90
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi renotubular syndrome 1
Mondo ID	MONDO:0024525
OMIM	134600
DOID	DOID:0080757
UMLS	C4551503
MedGen	1635492
GARD	0025412
Is cancer (heuristic)	no

Also known as: DeToni-Debré-Fanconi syndrome · Fanconi renotubular syndrome 1 · FRTS1 · primary Fanconi renal syndrome · primary Fanconi renotubular syndrome

Data availability: 90 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Fanconi renotubular syndrome › inherited Fanconi renotubular syndrome › primary Fanconi syndrome › Fanconi renotubular syndrome 1

Related subtypes (2): Fanconi renotubular syndrome 2, Fanconi renotubular syndrome 3

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

90 retrieved; paginated sample, class counts are floors:

62 uncertain significance, 13 likely benign, 3 benign, 3 benign/likely benign, 3 likely pathogenic, 3 pathogenic, 3 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
21299	NM_001482.3(GATM):c.484+1G>T	GATM	Pathogenic	reviewed by expert panel
55919	NM_001482.3(GATM):c.505C>T (p.Arg169Ter)	GATM	Pathogenic	reviewed by expert panel
917493	NM_001482.3(GATM):c.958C>T (p.Pro320Ser)	GATM	Pathogenic	no assertion criteria provided
1339450	NM_001482.3(GATM):c.259T>C (p.Cys87Arg)	GATM	Likely pathogenic	criteria provided, single submitter
1702865	NM_001482.3(GATM):c.965G>C (p.Arg322Pro)	GATM	Likely pathogenic	no assertion criteria provided
3577235	NM_001482.3(GATM):c.217_250dup (p.Glu84fs)	GATM	Likely pathogenic	criteria provided, single submitter
2176108	NM_001482.3(GATM):c.964C>A (p.Arg322=)	GATM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
423739	NM_001482.3(GATM):c.160G>A (p.Asp54Asn)	GATM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
651610	NM_001482.3(GATM):c.603A>C (p.Lys201Asn)	GATM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
548610	NM_001966.4(EHHADH):c.1816_1817insG (p.Thr606fs)	EHHADH	Uncertain significance	criteria provided, single submitter
1008214	NM_001482.3(GATM):c.1009A>G (p.Ile337Val)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1010115	NM_001482.3(GATM):c.859C>T (p.Pro287Ser)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1018056	NM_001482.3(GATM):c.932T>C (p.Ile311Thr)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034931	NM_001482.3(GATM):c.875A>G (p.His292Arg)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1037641	NM_001482.3(GATM):c.813+6C>T	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1043107	NM_001482.3(GATM):c.1186C>A (p.Arg396Ser)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1320890	NM_001482.3(GATM):c.76C>G (p.Arg26Gly)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1349852	NM_001482.3(GATM):c.61G>A (p.Gly21Arg)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1375020	NM_001482.3(GATM):c.371T>C (p.Val124Ala)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1388303	NM_001482.3(GATM):c.378A>T (p.Glu126Asp)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1431172	NM_001482.3(GATM):c.1000G>A (p.Gly334Arg)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1435102	NM_001482.3(GATM):c.104C>A (p.Thr35Asn)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1461940	NM_001482.3(GATM):c.88G>A (p.Gly30Arg)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1476548	NM_001482.3(GATM):c.990C>G (p.Phe330Leu)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
1997517	NM_001482.3(GATM):c.715G>T (p.Ala239Ser)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
2039081	NM_001482.3(GATM):c.460A>G (p.Lys154Glu)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
2054525	NM_001482.3(GATM):c.167C>A (p.Ala56Asp)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
205611	NM_001482.3(GATM):c.279C>G (p.Ile93Met)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
205614	NM_001482.3(GATM):c.519A>G (p.Ile173Met)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
205620	NM_001482.3(GATM):c.145T>C (p.Ser49Pro)	GATM	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
GATM	Strong	Autosomal dominant	Fanconi renotubular syndrome 1	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GATM	Orphanet:3337	Primary Fanconi renotubular syndrome
GATM	Orphanet:35704	L-Arginine:glycine amidinotransferase deficiency
EHHADH	Orphanet:300	Bifunctional enzyme deficiency
EHHADH	Orphanet:3337	Primary Fanconi renotubular 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
GATM	HGNC:4175	ENSG00000171766	P50440	Glycine amidinotransferase, mitochondrial	gencc,clinvar
EHHADH	HGNC:3247	ENSG00000113790	Q08426	Peroxisomal bifunctional enzyme	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GATM	Glycine amidinotransferase, mitochondrial	Transamidinase that catalyzes the transfer of the amidino group of L-arginine onto the amino moiety of acceptor metabolites such as glycine, beta-alanine, gamma-aminobutyric acid (GABA) and taurine yielding the corresponding guanidine deri…
EHHADH	Peroxisomal bifunctional enzyme	Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GATM	Enzyme (other)	yes	2.1.4.1	AmidinoTrfase
EHHADH	Other/Unknown	no		Enoyl-CoA_hydra/iso, 3HC_DH_C, 3-OHacyl-CoA_DH_NAD-bd

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
right lobe of liver	2
adult organism	1
body of pancreas	1
liver	1
nephron tubule	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GATM	289	ubiquitous	marker	body of pancreas, adult organism, right lobe of liver
EHHADH	241	ubiquitous	marker	right lobe of liver, liver, nephron tubule

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EHHADH	3,281
GATM	2,658

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GATM	P50440	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EHHADH	Q08426	95.07

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
Creatine metabolism	1	519.1×	0.003	GATM
Beta-oxidation of very long chain fatty acids	1	439.2×	0.003	EHHADH
Peroxisomal protein import	1	86.5×	0.012	EHHADH

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
creatine biosynthetic process	1	4213.0×	0.001	GATM
muscle atrophy	1	4213.0×	0.001	GATM
creatine metabolic process	1	2106.5×	0.002	GATM
fatty acid derivative biosynthetic process	1	766.0×	0.004	EHHADH
fatty acid beta-oxidation using acyl-CoA oxidase	1	561.7×	0.004	EHHADH
alpha-linolenic acid metabolic process	1	443.5×	0.004	EHHADH
unsaturated fatty acid biosynthetic process	1	324.1×	0.005	EHHADH
long-chain fatty acid biosynthetic process	1	221.7×	0.006	EHHADH
fatty acid beta-oxidation	1	187.2×	0.007	EHHADH
learning or memory	1	120.4×	0.009	GATM
positive regulation of cold-induced thermogenesis	1	81.8×	0.012	GATM

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
GATM	0	0
EHHADH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GATM	2.1.4.1	glycine amidinotransferase

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	1	GATM
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	EHHADH

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)
GATM	0	—
EHHADH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases