Nephrocalcinosis

Summary

Nephrocalcinosis (MONDO:0001567) is a disease caused by PKHD1 (GenCC Strong), with 11 cohort genes and 9 clinical trials. Top therapeutic interventions include potassium citrate anhydrous, citric acid, and fluconazole.

At a glance

• Causal gene: PKHD1 (GenCC Strong)
• Cohort genes: 11
• ClinVar variants: 22
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrocalcinosis
Mondo ID	MONDO:0001567
MeSH	D009397
DOID	DOID:12679
ICD-11	1359282431
NCIT	C84918
SNOMED CT	48638002
UMLS	C0027709
MedGen	10222
Is cancer (heuristic)	no

Also known as: hypercalcemic nephropathy

Data availability: 22 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › mineral metabolism disease › calcium metabolic disease › calcinosis › nephrocalcinosis

Related subtypes (2): calciphylaxis, familial tumoral calcinosis

Subtypes (1): renal hypomagnesemia 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

22 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
204105	NM_000030.3(AGXT):c.481G>A (p.Gly161Ser)	AGXT	Pathogenic	criteria provided, multiple submitters, no conflicts
5644	NM_000030.3(AGXT):c.121G>A (p.Gly41Arg)	AGXT	Pathogenic	criteria provided, multiple submitters, no conflicts
5646	NM_000030.3(AGXT):c.731T>C (p.Ile244Thr)	AGXT	Pathogenic	criteria provided, multiple submitters, no conflicts
12228	NM_001692.4(ATP6V1B1):c.242T>C (p.Leu81Pro)	ATP6V1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
638151	NM_001692.4(ATP6V1B1):c.175-1G>C	ATP6V1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
548673	NM_012203.2(GRHPR):c.404+5G>A	GRHPR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5636	NM_012203.2(GRHPR):c.103del (p.Asp35fs)	GRHPR	Pathogenic	criteria provided, multiple submitters, no conflicts
265999	NM_000338.3(SLC12A1):c.1163del (p.Phe388fs)	SLC12A1	Pathogenic	criteria provided, single submitter
548675	NM_000338.3(SLC12A1):c.769G>A (p.Gly257Ser)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
234926	NM_003052.5(SLC34A1):c.644+1G>A	SLC34A1	Pathogenic	criteria provided, multiple submitters, no conflicts
548674	NM_000341.4(SLC3A1):c.592del (p.Ala198fs)	SLC3A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
548671	NM_000030.3(AGXT):c.1079G>C (p.Arg360Pro)	AGXT	Likely pathogenic	no assertion criteria provided
3767995	NM_015365.3(AMMECR1):c.790+1G>A	AMMECR1	Likely pathogenic	criteria provided, single submitter
1804036	NM_001256071.3(RNF213):c.114C>G (p.Asn38Lys)	RNF213	Likely pathogenic	criteria provided, single submitter
548676	NM_000338.3(SLC12A1):c.1424G>A (p.Cys475Tyr)	SLC12A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
548672	NM_148960.3(CLDN19):c.535G>A (p.Gly179Ser)	CLDN19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
352960	NM_003052.5(SLC34A1):c.398C>T (p.Ala133Val)	SLC34A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
548679	NM_003052.5(SLC34A1):c.1724C>T (p.Thr575Ile)	SLC34A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5931	NM_006580.4(CLDN16):c.485T>G (p.Phe162Cys)	CLDN16	Uncertain significance	criteria provided, single submitter
548678	NM_003052.5(SLC34A1):c.1204G>C (p.Gly402Arg)	SLC34A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
548680	NM_003052.5(SLC34A1):c.536T>C (p.Leu179Pro)	SLC34A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
988206	NM_003052.5(SLC34A1):c.1715G>A (p.Trp572Ter)	SLC34A1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 18 · 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
PKHD1	Strong	Autosomal dominant	nephrocalcinosis	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PKHD1	Orphanet:53035	Caroli disease
PKHD1	Orphanet:731	Autosomal recessive polycystic kidney 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
SLC3A1	Orphanet:163690	Hypotonia-cystinuria syndrome
SLC3A1	Orphanet:163693	2p21 microdeletion syndrome
SLC3A1	Orphanet:238523	Atypical hypotonia-cystinuria syndrome
SLC3A1	Orphanet:93612	Cystinuria type A
RNF213	Orphanet:2573	Moyamoya disease
CLDN16	Orphanet:31043	Primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement
CLDN19	Orphanet:2196	Primary hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement
AGXT	Orphanet:93598	Primary hyperoxaluria type 1
GRHPR	Orphanet:93599	Primary hyperoxaluria type 2
AMMECR1	Orphanet:688581	Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome
AMMECR1	Orphanet:86818	Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
ATP6V1B1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PKHD1	HGNC:9016	ENSG00000170927	P08F94	Fibrocystin	gencc
SLC12A1	HGNC:10910	ENSG00000074803	Q13621	Solute carrier family 12 member 1	clinvar
SLC34A1	HGNC:11019	ENSG00000131183	Q06495	Sodium-dependent phosphate transport protein 2A	clinvar
SLC3A1	HGNC:11025	ENSG00000138079	Q07837	Amino acid transporter heavy chain SLC3A1	clinvar
RNF213	HGNC:14539	ENSG00000173821	Q63HN8	E3 ubiquitin-protein ligase RNF213	clinvar
CLDN16	HGNC:2037	ENSG00000113946	Q9Y5I7	Claudin-16	clinvar
CLDN19	HGNC:2040	ENSG00000164007	Q8N6F1	Claudin-19	clinvar
AGXT	HGNC:341	ENSG00000172482	P21549	Alanine–glyoxylate aminotransferase	clinvar
GRHPR	HGNC:4570	ENSG00000137106	Q9UBQ7	Glyoxylate reductase/hydroxypyruvate reductase	clinvar
AMMECR1	HGNC:467	ENSG00000101935	Q9Y4X0	Nuclear protein AMMECR1	clinvar
ATP6V1B1	HGNC:853	ENSG00000116039	P15313	V-type proton ATPase subunit B, kidney isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PKHD1	Fibrocystin	Promotes ciliogenesis in renal epithelial cells and therefore participates in the tubules formation and/ or ensures the maintenance of the architecture of the lumen of the kidney.
SLC12A1	Solute carrier family 12 member 1	Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation.
SLC34A1	Sodium-dependent phosphate transport protein 2A	Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.
SLC3A1	Amino acid transporter heavy chain SLC3A1	Acts as a chaperone that facilitates biogenesis and trafficking of functional transporter heteromers to the plasma membrane.
RNF213	E3 ubiquitin-protein ligase RNF213	Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.
CLDN16	Claudin-16	Forms paracellular channels: coassembles with CLDN19 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.
CLDN19	Claudin-19	Forms paracellular channels: coassembles with CLDN16 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.
AGXT	Alanine–glyoxylate aminotransferase	Peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification.
GRHPR	Glyoxylate reductase/hydroxypyruvate reductase	Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities.
ATP6V1B1	V-type proton ATPase subunit B, kidney isoform	Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 7 · Druggable fraction: 0.27

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
Antibody/Immunoglobulin	1	2.6×	0.558
Enzyme (other)	2	2.2×	0.558
Other/Unknown	7	1.1×	0.558
Transcription factor	1	0.8×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PKHD1	Antibody/Immunoglobulin	yes		IPT_dom, PbH1, Pectin_lyase_fold/virulence
SLC12A1	Other/Unknown	no		SLC12A1/SLC12A2, Slc12a1, AA-permease/SLC12A_dom
SLC34A1	Other/Unknown	no		Na/Pi_transpt
SLC3A1	Other/Unknown	no		GH13_cat_dom, Glyco_hydro_b, GH_hydrolase_sf
RNF213	Transcription factor	no		Znf_RING, AAA+_ATPase, Znf_RING/FYVE/PHD
CLDN16	Other/Unknown	no		Claudin16, PMP22/EMP/MP20/Claudin, Claudin
CLDN19	Other/Unknown	no		PMP22/EMP/MP20/Claudin, Claudin, Claudin_CS
AGXT	Enzyme (other)	yes	2.6.1.44	Aminotrans_V_dom, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
GRHPR	Enzyme (other)	yes	1.1.1.26	D-isomer_2_OHA_DH_cat_dom, D-isomer_DH_NAD-bd, D-isomer_DH_CS
AMMECR1	Other/Unknown	no		AMMECR1_domain, AMMECR1, AMMECR1_N
ATP6V1B1	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu

Expression context

Cohort genes with no expression data: 0.

11 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)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
metanephros cortex	5
kidney epithelium	2
renal medulla	2
nephron tubule	2
adult mammalian kidney	2
male germ line stem cell (sensu Vertebrata) in testis	2
liver	2
right lobe of liver	2
body of pancreas	1
gall bladder	1
granulocyte	1
pancreatic ductal cell	1
olfactory segment of nasal mucosa	1
dorsal root ganglion	1
pigmented layer of retina	1
trigeminal ganglion	1
endometrium epithelium	1
right adrenal gland	1
buccal mucosa cell	1
esophagus squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PKHD1	51	tissue_specific	marker	kidney epithelium, renal medulla, metanephros cortex
SLC12A1	185	tissue_specific	marker	renal medulla, nephron tubule, metanephros cortex
SLC34A1	52	tissue_specific	marker	nephron tubule, adult mammalian kidney, kidney epithelium
SLC3A1	163	tissue_specific	marker	body of pancreas, gall bladder, metanephros cortex
RNF213	252	ubiquitous	marker	granulocyte, metanephros cortex, pancreatic ductal cell
CLDN16	127	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa, adult mammalian kidney
CLDN19	143	broad	marker	trigeminal ganglion, dorsal root ganglion, pigmented layer of retina
AGXT	125	tissue_specific	marker	right lobe of liver, liver, endometrium epithelium
GRHPR	292	ubiquitous	marker	right lobe of liver, liver, right adrenal gland
AMMECR1	262	ubiquitous	marker	esophagus squamous epithelium, buccal mucosa cell, trabecular bone tissue
ATP6V1B1	152	broad	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC34A1	3,362
GRHPR	2,785
AGXT	2,648
RNF213	2,368
ATP6V1B1	2,172
SLC3A1	1,890
SLC12A1	1,448
PKHD1	1,211
CLDN19	979
AMMECR1	899

Intra-cohort edges

A	B	Sources
AGXT	GRHPR	string_interaction
CLDN16	CLDN19	intact, string_interaction
CLDN19	SLC12A1	string_interaction
GRHPR	SLC3A1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AGXT	P21549	17
SLC3A1	Q07837	5
RNF213	Q63HN8	4
GRHPR	Q9UBQ7	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP6V1B1	P15313	87.21
CLDN19	Q8N6F1	81.08
SLC12A1	Q13621	78.39
CLDN16	Q9Y5I7	76.74
AMMECR1	Q9Y4X0	75.18
SLC34A1	Q06495	72.24
PKHD1	P08F94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. Enrichment computed across 11 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glyoxylate metabolism and glycine degradation	2	169.2×	0.002	AGXT, GRHPR
Tight junction interactions	2	81.9×	0.005	CLDN16, CLDN19
Defective SLC12A1 causes Bartter syndrome 1 (BS1)	1	1268.9×	0.008	SLC12A1
SLC transporter disorders	2	45.3×	0.008	SLC12A1, SLC3A1
Defective SLC34A1 causes hypophosphatemic nephrolithiasis/osteoporosis 1 (NPHLOP1)	1	634.4×	0.008	SLC34A1
Defective SLC3A1 causes cystinuria (CSNU)	1	634.4×	0.008	SLC3A1
Defective amino acid transport by SLC7A9 causes cystinuria (CSNU)	1	634.4×	0.008	SLC3A1
Disorders of transmembrane transporters	2	30.9×	0.008	SLC12A1, SLC3A1
R-HSA-425393	2	28.8×	0.008	SLC12A1, SLC3A1
Type II Na+/Pi cotransporters	1	317.2×	0.012	SLC34A1
Cation-coupled Chloride cotransporters	1	181.3×	0.017	SLC12A1
Suppression of apoptosis	1	181.3×	0.017	RNF213
Response of Mtb to phagocytosis	1	158.6×	0.018	RNF213
Infection with Mycobacterium tuberculosis	1	126.9×	0.021	RNF213
SLC-mediated transmembrane transport	2	13.2×	0.023	SLC12A1, SLC3A1
Insulin receptor recycling	1	42.3×	0.047	ATP6V1B1
Surfactant metabolism	1	40.9×	0.047	SLC34A1
Transferrin endocytosis and recycling	1	40.9×	0.047	ATP6V1B1
ROS and RNS production in phagocytes	1	37.3×	0.047	ATP6V1B1
Bacterial Infection Pathways	1	37.3×	0.047	RNF213
Disease	3	4.4×	0.047	SLC12A1, SLC3A1, RNF213
Amino acid transport across the plasma membrane	1	33.4×	0.050	SLC3A1
Signaling by ALK in cancer	1	30.2×	0.052	RNF213
Amino acids regulate mTORC1	1	22.3×	0.067	ATP6V1B1
Protein localization	1	21.1×	0.067	AGXT
Transport of small molecules	2	5.6×	0.067	SLC12A1, SLC3A1
Peroxisomal protein import	1	19.2×	0.070	AGXT
Signaling by ALK fusions and activated point mutants	1	16.7×	0.077	RNF213
Ion channel transport	1	10.7×	0.115	ATP6V1B1
Class I MHC mediated antigen processing & presentation	1	7.8×	0.150	RNF213

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glyoxylate metabolic process	2	561.7×	4e-04	AGXT, GRHPR
paracellular transport	2	481.5×	4e-04	CLDN16, CLDN19
renal absorption	2	337.0×	6e-04	CLDN16, CLDN19
chloride ion homeostasis	2	306.4×	6e-04	SLC12A1, ATP6V1B1
calcium-independent cell-cell adhesion	2	160.5×	0.002	CLDN16, CLDN19
potassium ion homeostasis	2	153.2×	0.002	SLC12A1, ATP6V1B1
intercellular transport	1	1685.2×	0.007	CLDN16
basic amino acid transport	1	1685.2×	0.007	SLC3A1
lipid ubiquitination	1	1685.2×	0.007	RNF213
regulation of cholangiocyte proliferation	1	1685.2×	0.007	PKHD1
bicellular tight junction assembly	2	66.1×	0.007	CLDN16, CLDN19
ossification	2	45.5×	0.009	SLC34A1, ATP6V1B1
indole metabolic process	1	842.6×	0.009	SLC34A1
dicarboxylic acid metabolic process	1	842.6×	0.009	GRHPR
gentamycin metabolic process	1	842.6×	0.009	SLC34A1
arsenate ion transmembrane transport	1	842.6×	0.009	SLC34A1
positive regulation of phosphate transmembrane transport	1	842.6×	0.009	SLC34A1
obsolete glycine biosynthetic process, by transamination of glyoxylate	1	561.7×	0.011	AGXT
oxalic acid secretion	1	561.7×	0.011	AGXT
renal tubular secretion	1	561.7×	0.011	ATP6V1B1
renal sodium ion transport	1	421.3×	0.011	ATP6V1B1
glyoxylate catabolic process	1	421.3×	0.011	AGXT
cellular response to phosphate starvation	1	421.3×	0.011	SLC34A1
L-cysteine catabolic process	1	421.3×	0.011	AGXT
renal sodium excretion	1	421.3×	0.011	ATP6V1B1
L-alanine catabolic process	1	421.3×	0.011	AGXT
cellular response to metal ion	1	421.3×	0.011	SLC34A1
regulation of transepithelial transport	1	421.3×	0.011	CLDN19
positive regulation of sodium-dependent phosphate transport	1	421.3×	0.011	SLC34A1
kidney development	2	28.1×	0.011	SLC34A1, PKHD1

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Citric Acid	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 10

Druggability breadth: 7 of 11 evidence-associated genes (64%) 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
PKHD1	0	0
SLC12A1	0	0
SLC3A1	0	0
RNF213	0	0
CLDN16	0	0
CLDN19	0	0
AGXT	0	0
GRHPR	0	0
AMMECR1	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): 2.

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

Symbol	Assays	Type breakdown
SLC34A1	8	Binding:7, Functional:1
AGXT	8	Binding:8
AMMECR1	6	Binding:6
GRHPR	2	Binding:2
RNF213	1	Binding:1
ATP6V1B1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AGXT	2.6.1.44, 2.6.1.51	alanine-glyoxylate transaminase, serine-pyruvate transaminase
GRHPR	1.1.1.26, 1.1.1.79, 1.1.1.81	glyoxylate reductase, glyoxylate reductase (NADP+), hydroxypyruvate reductase

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; 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	2	AGXT, GRHPR
D	Druggable family + AlphaFold only, no drug	1	PKHD1
E	Difficult family or no structure, no drug	7	SLC12A1, SLC3A1, RNF213, CLDN16, CLDN19, AMMECR1, ATP6V1B1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKHD1	0	—
SLC12A1	0	—
SLC3A1	0	—
RNF213	1	—
CLDN16	0	—
CLDN19	0	—
AGXT	8	—
GRHPR	2	—
AMMECR1	6	—
ATP6V1B1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE3	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00249951	PHASE3	COMPLETED	Alkaline Citrate Treatment to Lower the Risk of Nephrocalcinosis in Preterm Infants
NCT01756547	PHASE3	UNKNOWN	Study to Assess the Efficacy and Safety of Oral Potassium Citrate on the Prevention of Nephrocalcinosis in Extreme Premature
NCT04495608	PHASE2	COMPLETED	Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Fluconazole in Hypercalcicuric Patients With Increased 1.25(OH) 2D Levels
NCT00169806	Not specified	ACTIVE_NOT_RECRUITING	Randall’s Plaque Study: Pathogenesis and Relationship to Nephrolithiasis
NCT07435844	Not specified	RECRUITING	Effect of Comprehensive Spa Care on Kidney and Urological Conditions: A Clinical Study in Adult Patients
NCT00875823	Not specified	WITHDRAWN	International Registry for Primary Hyperoxaluria
NCT02438267	Not specified	COMPLETED	Preterm Infants and Nephrocalcinosis
NCT04382976	Not specified	COMPLETED	The Incidence and the Risk Factors of Nephrocalcinosis in Very Preterm Infants
NCT05862207	Not specified	UNKNOWN	Prevalence and Risk Factors of Nephrocalcinosis in Children at Sohag University Hospital

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
POTASSIUM CITRATE ANHYDROUS	4	2
CITRIC ACID	4	1
FLUCONAZOLE	4	1