primary Fanconi syndrome

Summary

primary Fanconi syndrome (MONDO:0007600) is a disease with 4 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• Phenotypes (HPO): 29
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0000117	Renal phosphate wasting	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0002049	Proximal renal tubular acidosis	Very frequent (80-99%)
HP:0002909	Generalized aminoaciduria	Very frequent (80-99%)
HP:0003076	Glycosuria	Very frequent (80-99%)
HP:0003126	Low-molecular-weight proteinuria	Very frequent (80-99%)
HP:0003149	Hyperuricosuria	Very frequent (80-99%)
HP:0003646	Bicarbonaturia	Very frequent (80-99%)
HP:0004910	Bicarbonate-wasting renal tubular acidosis	Very frequent (80-99%)
HP:0004918	Hyperchloremic metabolic acidosis	Very frequent (80-99%)
HP:0032943	Abnormal urine pH	Very frequent (80-99%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002148	Hypophosphatemia	Frequent (30-79%)
HP:0002653	Bone pain	Frequent (30-79%)
HP:0002659	Increased susceptibility to fractures	Frequent (30-79%)
HP:0002749	Osteomalacia	Frequent (30-79%)
HP:0002900	Hypokalemia	Frequent (30-79%)
HP:0003081	Increased urinary potassium	Frequent (30-79%)
HP:0003234	Decreased circulating carnitine concentration	Frequent (30-79%)
HP:0003537	Hypouricemia	Frequent (30-79%)
HP:0004912	Hypophosphatemic rickets	Frequent (30-79%)
HP:0012606	Renal sodium wasting	Frequent (30-79%)
HP:0012622	Chronic kidney disease	Frequent (30-79%)
HP:0001944	Dehydration	Occasional (5-29%)
HP:0002150	Hypercalciuria	Occasional (5-29%)
HP:0003774	Stage 5 chronic kidney disease	Occasional (5-29%)
HP:0001943	Hypoglycemia	Very rare (<1-4%)
HP:0002206	Pulmonary fibrosis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	primary Fanconi syndrome
Mondo ID	MONDO:0007600
Orphanet	3337
NCIT	C123229
UMLS	C1857395
MedGen	341765
GARD	0009118
Is cancer (heuristic)	no

Also known as: Fanconi renotubular syndrome 1 · FRTS1 · primary Fanconi renotubular syndrome

Data availability: 4 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (2): Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young, Fanconi renotubular syndrome 5

Subtypes (3): Fanconi renotubular syndrome 2, Fanconi renotubular syndrome 3, 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 29 · Orphanet: 9 · 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
EHHADH	Strong	Autosomal dominant	Fanconi renotubular syndrome 3	4
GATM	Strong	Autosomal dominant	Fanconi renotubular syndrome 1	10
NDUFAF6	Supportive	Autosomal dominant	primary Fanconi syndrome	5
SLC34A1	Supportive	Autosomal dominant	primary Fanconi syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC34A1	Orphanet:157215	Hereditary hypophosphatemic rickets with hypercalciuria
SLC34A1	Orphanet:244305	Dominant hypophosphatemia with nephrolithiasis or osteoporosis
SLC34A1	Orphanet:300547	Autosomal recessive infantile hypercalcemia
SLC34A1	Orphanet:3337	Primary Fanconi renotubular syndrome
NDUFAF6	Orphanet:3337	Primary Fanconi renotubular syndrome
EHHADH	Orphanet:300	Bifunctional enzyme deficiency
EHHADH	Orphanet:3337	Primary Fanconi renotubular syndrome
GATM	Orphanet:3337	Primary Fanconi renotubular syndrome
GATM	Orphanet:35704	L-Arginine:glycine amidinotransferase deficiency

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC34A1	HGNC:11019	ENSG00000131183	Q06495	Sodium-dependent phosphate transport protein 2A	gencc
NDUFAF6	HGNC:28625	ENSG00000156170	Q330K2	NADH dehydrogenase (ubiquinone) complex I, assembly factor 6	gencc
EHHADH	HGNC:3247	ENSG00000113790	Q08426	Peroxisomal bifunctional enzyme	gencc
GATM	HGNC:4175	ENSG00000171766	P50440	Glycine amidinotransferase, mitochondrial	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC34A1	Sodium-dependent phosphate transport protein 2A	Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.
NDUFAF6	NADH dehydrogenase (ubiquinone) complex I, assembly factor 6	Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages.
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.
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…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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	3.0×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC34A1	Other/Unknown	no		Na/Pi_transpt
NDUFAF6	Other/Unknown	no		Squ/phyt_synthse, Isoprenoid_synthase_dom_sf
EHHADH	Other/Unknown	no		Enoyl-CoA_hydra/iso, 3HC_DH_C, 3-OHacyl-CoA_DH_NAD-bd
GATM	Enzyme (other)	yes	2.1.4.1	AmidinoTrfase

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
nephron tubule	2
right lobe of liver	2
adult mammalian kidney	1
kidney epithelium	1
deltoid	1
right uterine tube	1
tibialis anterior	1
liver	1
adult organism	1
body of pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC34A1	52	tissue_specific	marker	nephron tubule, adult mammalian kidney, kidney epithelium
NDUFAF6	242	ubiquitous	marker	right uterine tube, tibialis anterior, deltoid
EHHADH	241	ubiquitous	marker	right lobe of liver, liver, nephron tubule
GATM	289	ubiquitous	marker	body of pancreas, adult organism, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC34A1	3,362
EHHADH	3,281
GATM	2,658
NDUFAF6	1,990

Intra-cohort edges

A	B	Sources
GATM	SLC34A1	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 3 · 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
NDUFAF6	Q330K2	87.70
SLC34A1	Q06495	72.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC34A1 causes hypophosphatemic nephrolithiasis/osteoporosis 1 (NPHLOP1)	1	1427.5×	0.007	SLC34A1
Type II Na+/Pi cotransporters	1	713.8×	0.007	SLC34A1
Creatine metabolism	1	259.6×	0.011	GATM
Beta-oxidation of very long chain fatty acids	1	219.6×	0.011	EHHADH
Surfactant metabolism	1	92.1×	0.022	SLC34A1
Peroxisomal protein import	1	43.3×	0.034	EHHADH
Complex I biogenesis	1	41.4×	0.034	NDUFAF6
Respiratory electron transport	1	23.8×	0.049	NDUFAF6
Aerobic respiration and respiratory electron transport	1	22.1×	0.049	NDUFAF6
Metabolism	1	2.9×	0.302	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 4 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	2106.5×	0.003	GATM
muscle atrophy	1	2106.5×	0.003	GATM
indole metabolic process	1	2106.5×	0.003	SLC34A1
gentamycin metabolic process	1	2106.5×	0.003	SLC34A1
arsenate ion transmembrane transport	1	2106.5×	0.003	SLC34A1
positive regulation of phosphate transmembrane transport	1	2106.5×	0.003	SLC34A1
creatine metabolic process	1	1053.2×	0.004	GATM
cellular response to phosphate starvation	1	1053.2×	0.004	SLC34A1
cellular response to metal ion	1	1053.2×	0.004	SLC34A1
positive regulation of sodium-dependent phosphate transport	1	1053.2×	0.004	SLC34A1
cellular response to staurosporine	1	842.6×	0.005	SLC34A1
positive regulation of membrane potential	1	702.2×	0.005	SLC34A1
tricarboxylic acid metabolic process	1	702.2×	0.005	SLC34A1
response to mercury ion	1	601.9×	0.005	SLC34A1
response to potassium ion	1	526.6×	0.005	SLC34A1
response to thyroid hormone	1	526.6×	0.005	SLC34A1
dentinogenesis	1	526.6×	0.005	SLC34A1
phosphate ion transport	1	468.1×	0.005	SLC34A1
sodium-dependent phosphate transport	1	468.1×	0.005	SLC34A1
intracellular phosphate ion homeostasis	1	383.0×	0.005	SLC34A1
fatty acid derivative biosynthetic process	1	383.0×	0.005	EHHADH
response to magnesium ion	1	351.1×	0.005	SLC34A1
cellular response to parathyroid hormone stimulus	1	351.1×	0.005	SLC34A1
phosphate ion transmembrane transport	1	300.9×	0.006	SLC34A1
glycoprotein metabolic process	1	280.9×	0.006	SLC34A1
fatty acid beta-oxidation using acyl-CoA oxidase	1	280.9×	0.006	EHHADH
response to growth hormone	1	280.9×	0.006	SLC34A1
response to peptide	1	280.9×	0.006	SLC34A1
response to vitamin A	1	263.3×	0.006	SLC34A1
phosphate ion homeostasis	1	263.3×	0.006	SLC34A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) 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
SLC34A1	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC34A1	2	4
NDUFAF6	0	0
EHHADH	0	0
GATM	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SLC34A1	8	Binding:7, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GATM	2.1.4.1	glycine amidinotransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 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)
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC34A1
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	2	NDUFAF6, EHHADH

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NDUFAF6	0	—
EHHADH	0	—
GATM	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