Hypophosphatemic rickets

Summary

Hypophosphatemic rickets (MONDO:0024300) is a disease with 8 cohort genes and 9 clinical trials. Top therapeutic interventions include cinacalcet, burosumab, and calcitriol.

At a glance

• Cohort genes: 8
• ClinVar variants: 34
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypophosphatemic rickets
Mondo ID	MONDO:0024300
MeSH	D063730
NCIT	C131449
UMLS	C1704375
MedGen	309957
GARD	0025385
Is cancer (heuristic)	no

Also known as: acquired vitamin D resistant rickets · acquired vitamin D-resistant rickets · hypophosphatemia, vitamin D-resistant rickets · hypophosphatemic Ricket · hypophosphatemic rickets · hypophosphatemic vitamin D resistant rickets · hypophosphatemic vitamin D-resistant rickets · Phosphopenic rickets · Ricket, hypophosphatemic · rickets, vitamin D resistant · rickets, vitamin D-resistant · vitamin D-resistant rickets

Data availability: 34 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone remodeling disease › rickets › hypophosphatemic rickets

Related subtypes (3): renal osteodystrophy, hypocalcemic rickets, vitamin D-dependent rickets

Subtypes (1): hereditary hypophosphatemic rickets

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

34 retrieved; paginated sample, class counts are floors:

21 pathogenic, 4 likely pathogenic, 4 conflicting classifications of pathogenicity, 3 uncertain significance, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1339444	NM_004407.4(DMP1):c.2T>A (p.Met1Lys)	DMP1	Pathogenic	criteria provided, single submitter
36135	NM_020638.3(FGF23):c.536G>A (p.Arg179Gln)	FGF23	Pathogenic	criteria provided, multiple submitters, no conflicts
1339438	NM_000444.6(PHEX):c.567_568del (p.Gln189fs)	PHEX	Pathogenic	criteria provided, single submitter
1339439	NM_000444.6(PHEX):c.652_655del (p.His218fs)	PHEX	Pathogenic	criteria provided, single submitter
1339440	NM_000444.6(PHEX):c.665_674del	PHEX	Pathogenic	criteria provided, single submitter
1339442	NM_000444.6(PHEX):c.1965+1del	PHEX	Pathogenic	criteria provided, single submitter
1339443	NM_000444.6(PHEX):c.1336_1337insAATA (p.Phe446Ter)	PHEX	Pathogenic	criteria provided, single submitter
1339456	NM_000444.6(PHEX):c.2071-1G>C	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
1339458	NM_000444.6(PHEX):c.1966-1G>A	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
1339459	NM_000444.6(PHEX):c.663+1G>T	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
1339460	NM_000444.6(PHEX):c.1482+2T>A	PHEX	Pathogenic	criteria provided, single submitter
1339461	NM_000444.6(PHEX):c.826A>T (p.Arg276Ter)	PHEX	Pathogenic	criteria provided, single submitter
1343090	NM_000444.6(PHEX):c.1970A>G (p.Tyr657Cys)	PHEX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279976	NM_000444.6(PHEX):c.1768+1G>C	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
280076	NM_000444.6(PHEX):c.1601C>T (p.Pro534Leu)	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
372454	NM_000444.6(PHEX):c.871C>T (p.Arg291Ter)	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
374096	NM_000444.6(PHEX):c.2167_2170dup (p.Phe724Ter)	PHEX	Pathogenic	criteria provided, single submitter
419401	NM_000444.6(PHEX):c.1202del (p.Pro401fs)	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
420128	NM_000444.6(PHEX):c.985dup (p.His329fs)	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
438568	NM_000444.6(PHEX):c.1700+2T>C	PHEX	Pathogenic	criteria provided, multiple submitters, no conflicts
1339441	NM_000444.6(PHEX):c.1920_1929del (p.Gly641fs)	PTCHD1-AS	Pathogenic	criteria provided, single submitter
280082	NM_000444.6(PHEX):c.1979G>A (p.Trp660Ter)	PTCHD1-AS	Pathogenic	criteria provided, multiple submitters, no conflicts
1343811	NM_182758.4(WDR72):c.764_768del (p.Gly255fs)	WDR72	Pathogenic/Likely pathogenic	no assertion criteria provided
505906	NM_004407.4(DMP1):c.979C>T (p.Gln327Ter)	DMP1	Likely pathogenic	criteria provided, single submitter
1339437	NM_000444.6(PHEX):c.1316T>G (p.Val439Gly)	PHEX	Likely pathogenic	criteria provided, single submitter
1339446	NM_000444.6(PHEX):c.2048T>A (p.Leu683His)	PHEX	Likely pathogenic	criteria provided, single submitter
1343086	NM_000444.6(PHEX):c.229T>A (p.Cys77Ser)	PHEX	Likely pathogenic	criteria provided, single submitter
13589	NM_006208.3(ENPP1):c.517A>C (p.Lys173Gln)	ENPP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161093	NM_006208.3(ENPP1):c.1831C>G (p.Leu611Val)	ENPP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1343094	NM_000444.6(PHEX):c.2188G>T (p.Ala730Ser)	PHEX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 15 · 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
SGK3	Limited	Autosomal dominant	hypophosphatemic rickets	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR72	Orphanet:100033	Hypomaturation amelogenesis imperfecta
WDR72	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
DMP1	Orphanet:289176	Autosomal recessive hypophosphatemic rickets
ENPP1	Orphanet:289176	Autosomal recessive hypophosphatemic rickets
ENPP1	Orphanet:324561	Hypopigmentation-punctate palmoplantar keratoderma syndrome
ENPP1	Orphanet:51608	Generalized arterial calcification of infancy
ENPP1	Orphanet:758	Pseudoxanthoma elasticum
FGF23	Orphanet:306661	Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome
FGF23	Orphanet:89937	Autosomal dominant hypophosphatemic rickets
HRAS	Orphanet:146	Differentiated thyroid carcinoma
HRAS	Orphanet:2612	Linear nevus sebaceus syndrome
HRAS	Orphanet:2874	Phakomatosis pigmentokeratotica
HRAS	Orphanet:3071	Costello syndrome
HRAS	Orphanet:79414	Woolly hair nevus
PHEX	Orphanet:89936	X-linked hypophosphatemia

Cohort genes → proteins

8 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SGK3	HGNC:10812	ENSG00000104205	Q96BR1	Serine/threonine-protein kinase Sgk3	gencc
WDR72	HGNC:26790	ENSG00000166415	Q3MJ13	WD repeat-containing protein 72	clinvar
DMP1	HGNC:2932	ENSG00000152592	Q13316	Dentin matrix acidic phosphoprotein 1	clinvar
ENPP1	HGNC:3356	ENSG00000197594	P22413	Ectonucleotide pyrophosphatase/phosphodiesterase family member 1	clinvar
FGF23	HGNC:3680	ENSG00000118972	Q9GZV9	Fibroblast growth factor 23	clinvar
PTCHD1-AS	HGNC:37703	ENSG00000233067		PTCHD1 and PHEX antisense RNA	clinvar
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	clinvar
PHEX	HGNC:8918	ENSG00000102174	P78562	Phosphate-regulating neutral endopeptidase PHEX	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SGK3	Serine/threonine-protein kinase Sgk3	Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration.
WDR72	WD repeat-containing protein 72	Plays a major role in formation of tooth enamel.
DMP1	Dentin matrix acidic phosphoprotein 1	May have a dual function during osteoblast differentiation.
ENPP1	Ectonucleotide pyrophosphatase/phosphodiesterase family member 1	Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels.
FGF23	Fibroblast growth factor 23	Regulator of phosphate homeostasis.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
PHEX	Phosphate-regulating neutral endopeptidase PHEX	Peptidase that cleaves SIBLING (small integrin-binding ligand, N-linked glycoprotein)-derived ASARM peptides, thus regulating their biological activity.

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 3 · 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
Phosphatase	1	10.5×	0.509
Protease	1	4.6×	0.509
Kinase	1	3.5×	0.509
Scaffold/PPI	1	2.2×	0.569
Enzyme (other)	1	1.5×	0.602
Other/Unknown	3	0.7×	0.919

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SGK3	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, PX_dom
WDR72	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
DMP1	Other/Unknown	no		DMP1
ENPP1	Phosphatase	yes	3.6.1.9	Somatomedin_B_dom, Endo_G_ENPP1-like_dom, Phosphodiest/P_Trfase
FGF23	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
PTCHD1-AS	Other/Unknown	no
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
PHEX	Protease	yes	3.4.24.B15	Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C

Expression context

Cohort genes with no expression data: 0.

7 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tibia	3
corpus callosum	1
inferior vagus X ganglion	1
pigmented layer of retina	1
kidney epithelium	1
pancreatic ductal cell	1
renal medulla	1
male germ line stem cell (sensu Vertebrata) in testis	1
periodontal ligament	1
cartilage tissue	1
decidua	1
hair follicle	1
primordial germ cell in gonad	1
sural nerve	1
bone marrow cell	1
ganglionic eminence	1
pancreas	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SGK3	251	tissue_specific	marker	pigmented layer of retina, corpus callosum, inferior vagus X ganglion
WDR72	139	tissue_specific	marker	kidney epithelium, pancreatic ductal cell, renal medulla
DMP1	40	tissue_specific	marker	periodontal ligament, tibia, male germ line stem cell (sensu Vertebrata) in testis
ENPP1	227	ubiquitous	marker	tibia, decidua, cartilage tissue
FGF23	44	tissue_specific	marker	sural nerve, primordial germ cell in gonad, hair follicle
PTCHD1-AS	75		yes	bone marrow cell, ganglionic eminence, pancreas
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
PHEX	139	tissue_specific	marker	secondary oocyte, tibia, oocyte

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HRAS	8,064
ENPP1	1,911
SGK3	1,828
FGF23	1,533
WDR72	1,126
PHEX	856
DMP1	850
PTCHD1-AS	0

Intra-cohort edges

A	B	Sources
DMP1	FGF23	string_interaction
DMP1	PHEX	string_interaction
ENPP1	FGF23	string_interaction
ENPP1	PHEX	string_interaction
FGF23	PHEX	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HRAS	P01112	246
ENPP1	P22413	7
FGF23	Q9GZV9	6
SGK3	Q96BR1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PHEX	P78562	94.58
WDR72	Q3MJ13	67.22
DMP1	Q13316	47.80

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 102. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SHC-mediated cascade:FGFR3	2	240.4×	6e-04	FGF23, HRAS
FRS-mediated FGFR3 signaling	2	217.5×	6e-04	FGF23, HRAS
SHC-mediated cascade:FGFR4	2	217.5×	6e-04	FGF23, HRAS
SHC-mediated cascade:FGFR1	2	198.6×	6e-04	FGF23, HRAS
FRS-mediated FGFR4 signaling	2	198.6×	6e-04	FGF23, HRAS
Signaling by FGFR3 in disease	2	198.6×	6e-04	FGF23, HRAS
SHC-mediated cascade:FGFR2	2	190.3×	6e-04	FGF23, HRAS
FRS-mediated FGFR1 signaling	2	182.7×	6e-04	FGF23, HRAS
FRS-mediated FGFR2 signaling	2	175.7×	6e-04	FGF23, HRAS
Signaling by FGFR1 in disease	2	117.1×	0.001	FGF23, HRAS
Signaling by FGFR2 in disease	2	106.2×	0.001	FGF23, HRAS
Post-translational protein phosphorylation	2	40.1×	0.008	DMP1, FGF23
Signaling by RAS GAP mutants	1	761.3×	0.009	HRAS
Signaling by RAS GTPase mutants	1	761.3×	0.009	HRAS
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	2	34.6×	0.009	DMP1, FGF23
FGFR1c and Klotho ligand binding and activation	1	571.0×	0.011	FGF23
Activation of RAS in B cells	1	456.8×	0.013	HRAS
Vitamin B2 (riboflavin) metabolism	1	326.3×	0.014	ENPP1
RAS signaling downstream of NF1 loss-of-function variants	1	326.3×	0.014	HRAS
Estrogen-stimulated signaling through PRKCZ	1	326.3×	0.014	HRAS
SOS-mediated signalling	1	285.5×	0.014	HRAS
Activated NTRK3 signals through RAS	1	253.8×	0.014	HRAS
EGFR Transactivation by Gastrin	1	228.4×	0.014	HRAS
SHC-related events triggered by IGF1R	1	228.4×	0.014	HRAS
Activated NTRK2 signals through RAS	1	228.4×	0.014	HRAS
MET activates RAS signaling	1	207.6×	0.014	HRAS
Signaling by activated point mutants of FGFR1	1	190.3×	0.014	FGF23
Signaling by activated point mutants of FGFR3	1	190.3×	0.014	FGF23
Signaling by FGFR4 in disease	1	190.3×	0.014	HRAS
Activated NTRK2 signals through FRS2 and FRS3	1	190.3×	0.014	HRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to sodium phosphate	2	481.5×	3e-04	FGF23, PHEX
intracellular phosphate ion homeostasis	2	437.7×	3e-04	ENPP1, FGF23
cellular response to vitamin D	2	437.7×	3e-04	FGF23, PHEX
cellular response to parathyroid hormone stimulus	2	401.2×	3e-04	FGF23, PHEX
phosphate ion homeostasis	2	300.9×	4e-04	ENPP1, FGF23
negative regulation of bone mineralization	2	267.5×	4e-04	ENPP1, FGF23
biomineral tissue development	2	185.2×	7e-04	WDR72, DMP1
bone mineralization	2	77.7×	0.004	ENPP1, PHEX
obsolete positive regulation of vitamin D 24-hydroxylase activity	1	2407.4×	0.004	FGF23
organophosphate metabolic process	1	2407.4×	0.004	PHEX
obsolete negative regulation of hh target transcription factor activity	1	2407.4×	0.004	ENPP1
inorganic diphosphate transport	1	1203.7×	0.007	ENPP1
regulation of phosphate transport	1	802.5×	0.009	FGF23
regulation of enamel mineralization	1	802.5×	0.009	DMP1
positive regulation of miRNA metabolic process	1	802.5×	0.009	HRAS
regulation of cell population proliferation	2	33.0×	0.010	SGK3, HRAS
vitamin D catabolic process	1	601.9×	0.010	FGF23
nucleoside triphosphate catabolic process	1	481.5×	0.012	ENPP1
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	401.2×	0.012	FGF23
nucleic acid metabolic process	1	401.2×	0.012	ENPP1
response to insulin-like growth factor stimulus	1	401.2×	0.012	PHEX
positive regulation of ERK1 and ERK2 cascade	2	24.3×	0.013	FGF23, HRAS
oncogene-induced cell senescence	1	343.9×	0.013	HRAS
positive regulation of MAPK cascade	2	23.0×	0.013	FGF23, HRAS
negative regulation of glycogen biosynthetic process	1	300.9×	0.014	ENPP1
T-helper 1 type immune response	1	267.5×	0.014	HRAS
negative regulation of hormone secretion	1	267.5×	0.014	FGF23
cellular response to leptin stimulus	1	218.9×	0.017	FGF23
response to magnesium ion	1	200.6×	0.018	FGF23
negative regulation of D-glucose import across plasma membrane	1	172.0×	0.019	ENPP1

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Ergocalciferol	Approved (phase 4)

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Burosumab	Phase 3

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 5

Druggability breadth: 4 of 8 evidence-associated genes (50%) 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
SGK3	FEDRATINIB
HRAS	LONAFARNIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SGK3	13	4
HRAS	4	4
ENPP1	1	3
WDR72	0	0
DMP1	0	0
FGF23	0	0
PTCHD1-AS	0	0
PHEX	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	SGK3
NINTEDANIB	4	SGK3
SUNITINIB	4	SGK3
MIDOSTAURIN	4	SGK3
LONAFARNIB	4	HRAS
LINIFANIB	3	SGK3
DOVITINIB	3	SGK3
LESTAURTINIB	3	SGK3
RUBOXISTAURIN	3	SGK3
SURAMIN	3	ENPP1
SU-014813	2	SGK3
STALLIMYCIN	2	HRAS
KW-2449	1	SGK3
AT-13148	1	SGK3
GSK-690693	1	SGK3
AST-487	1	SGK3
L-778123 FREE BASE	1	HRAS
BMS-214662	1	HRAS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
SGK3	265	Binding:264, Functional:1
ENPP1	167	Binding:154, ADMET:13
HRAS	48	Binding:45, Functional:3
FGF23	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ENPP1	3.6.1.9	nucleotide diphosphatase
HRAS	3.6.5.2	small monomeric GTPase
PHEX	3.4.24.B15

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SGK3	265
ENPP1	167

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

18 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)
FEDRATINIB	4	SGK3
NINTEDANIB	4	SGK3
SUNITINIB	4	SGK3
MIDOSTAURIN	4	SGK3
LONAFARNIB	4	HRAS
LINIFANIB	3	SGK3
DOVITINIB	3	SGK3
LESTAURTINIB	3	SGK3
RUBOXISTAURIN	3	SGK3
SURAMIN	3	ENPP1
SU-014813	2	SGK3
STALLIMYCIN	2	HRAS
KW-2449	1	SGK3
AT-13148	1	SGK3
GSK-690693	1	SGK3
AST-487	1	SGK3
L-778123 FREE BASE	1	HRAS
BMS-214662	1	HRAS

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SGK3, HRAS
B	Phased (≥1) drug, not yet approved	1	ENPP1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	PHEX
E	Difficult family or no structure, no drug	4	WDR72, DMP1, FGF23, PTCHD1-AS

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PHEX	0	ENPP1
WDR72	0	—
DMP1	0	—
FGF23	2	—
PTCHD1-AS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE3	2
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01237288	PHASE3	COMPLETED	Therapeutic Use of Oral Sodium Phosphate (Z-521) in Primary Hypophosphatemic Rickets
NCT03581591	PHASE3	COMPLETED	Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets
NCT00473187	PHASE1	UNKNOWN	Effects of GH on Body Proportions and Final Height in X-Linked Hypophosphatemic Rickets
NCT03748966	EARLY_PHASE1	COMPLETED	Calcitriol Monotherapy for X-Linked Hypophosphatemia
NCT03651505	Not specified	ACTIVE_NOT_RECRUITING	X-linked Hypophosphatemia Disease Monitoring Program
NCT00844740	Not specified	WITHDRAWN	Calcimimetics in Hypophosphatemic Rickets
NCT01578824	Not specified	COMPLETED	Assessment Of Vitamin D Role In The Pathogenesis Of Asthma In Vitamin D Resistent Patients
NCT03348644	Not specified	COMPLETED	Milk Products in the Treatment of Hypophosphatemic Rickets
NCT04184661	Not specified	COMPLETED	Burosumab and 1-25 (OH) Vitamin D on Human Osteoclasts

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CINACALCET	4	3
BUROSUMAB	4	1
CALCITRIOL	4	1
SOMATROPIN	4	1