Hyperparathyroidism

Summary

Hyperparathyroidism (MONDO:0001741) is a disease with 3 cohort genes (8 GWAS associations across 13 studies) and 71 clinical trials. Top therapeutic interventions include cinacalcet, cholecalciferol, and methylene blue cation.

At a glance

• Cohort genes: 3
• GWAS associations: 8
• ClinVar variants: 49
• Clinical trials: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperparathyroidism
Mondo ID	MONDO:0001741
EFO	EFO:0008506
MeSH	D006961
DOID	DOID:13543
ICD-11	9633776
NCIT	C48259
SNOMED CT	66999008
UMLS	C0020502
MedGen	6967
Is cancer (heuristic)	no

Also known as: hyperparathyroidism

Data availability: 49 ClinVar variants · 8 GWAS associations (13 studies).

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › parathyroid gland disorder › hyperparathyroidism

Related subtypes (3): hypoparathyroidism, parathyroid hyperplasia, tumor of parathyroid gland

Subtypes (4): secondary hyperparathyroidism, primary hyperparathyroidism, hereditary hyperparathyroidism, tertiary hyperparathyroidism

Genetics & variants

GWAS landscape

8 GWAS associations across 13 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr6:10869648	4e-19		G	0.18
rs6906900	1e-18	TMEM14B - GCM2	T	0.17
rs149743155	1e-14	MIR6500 - C1orf185	T	0.47
rs3091842	8e-13	MAFB - RNA5SP484	G	0.3
rs78132596	8e-12	C1orf185	A	0.45
rs73885319	4e-11	APOL1	A	0.24
rs138668844	2e-09	CHD1-DT - LINC02113	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475693	Verma A	2024	5,490	442,955	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475692	Verma A	2024	2,152	118,432	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479894	Verma A	2024	2,152	118,432	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079753	Backman JD	2021	1,168	386,457	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083739	Backman JD	2021	1,168	386,457	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90435718	Zhou W	2018	781	405,386	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90477331	Verma A	2024	617	58,944	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079752	Backman JD	2021	512	387,308	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083738	Backman JD	2021	512	387,308	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90043642	Jiang L	2021	438	455,910	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	6

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	3
intergenic_variant	2
unknown	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr6:10869648				0.448			4e-19	Tier 4: intronic/intergenic
rs6906900	6	10853114	T>C,G	0.309	intron_variant	TMEM14B - GCM2	1e-18	Tier 4: intronic/intergenic
rs149743155	1	51082101	T>C	0.01	intergenic_variant	MIR6500 - C1orf185	1e-14	Tier 4: intronic/intergenic
rs3091842	20	40715632	G>A	0.04	intron_variant	MAFB - RNA5SP484	8e-13	Tier 4: intronic/intergenic
rs78132596	1	51115895	A>T	0.048	intron_variant	C1orf185	8e-12	Tier 4: intronic/intergenic
rs73885319	22	36265860	A>G	0.224	missense_variant	APOL1	4e-11	Tier 1: coding
rs138668844	5	99270750	T>A,C		intergenic_variant	CHD1-DT - LINC02113	2e-09	Tier 4: intronic/intergenic

ClinVar germline variants

49 retrieved; paginated sample, class counts are floors:

25 conflicting classifications of pathogenicity, 14 uncertain significance, 5 benign/likely benign, 4 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
818220	NM_018646.6(TRPV6):c.1978G>C (p.Gly660Arg)	TRPV6	Likely pathogenic	criteria provided, single submitter
21680	NM_024529.5(CDC73):c.-11G>A	CDC73	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136169	NM_001370259.2(MEN1):c.30G>T (p.Leu10=)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161294	NM_001370259.2(MEN1):c.511C>T (p.Arg171Trp)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161295	NM_001370259.2(MEN1):c.563C>T (p.Pro188Leu)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188099	NM_001370259.2(MEN1):c.1409C>T (p.Pro470Leu)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188265	NM_001370259.2(MEN1):c.1535C>T (p.Ser512Leu)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
200987	NM_001370259.2(MEN1):c.1618C>T (p.Pro540Ser)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215961	NM_001370259.2(MEN1):c.1351-4C>T	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215966	NM_001370259.2(MEN1):c.762G>A (p.Leu254=)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241822	NM_001370259.2(MEN1):c.655-6C>G	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
255616	NM_001370259.2(MEN1):c.1003C>A (p.Arg335=)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305302	NM_001370259.2(MEN1):c.*470A>G	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305313	NM_001370259.2(MEN1):c.1186-10C>T	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305314	NM_001370259.2(MEN1):c.327A>C (p.Glu109Asp)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305315	NM_001370259.2(MEN1):c.61C>A (p.Arg21Ser)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36519	NM_001370259.2(MEN1):c.1049+9C>T	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36524	NM_001370259.2(MEN1):c.1296G>A (p.Leu432=)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
412561	NM_001370259.2(MEN1):c.753C>T (p.Thr251=)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
412579	NM_001370259.2(MEN1):c.570G>A (p.Gly190=)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41854	NM_001370259.2(MEN1):c.512G>A (p.Arg171Gln)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41855	NM_001370259.2(MEN1):c.774G>C (p.Gln258His)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485711	NM_001370259.2(MEN1):c.941G>A (p.Arg314Gln)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
877570	NM_001370259.2(MEN1):c.849G>T (p.Leu283=)	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
880309	NM_001370259.2(MEN1):c.*126C>T	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96253	NM_001370259.2(MEN1):c.655-6C>T	MEN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305303	NM_001370259.2(MEN1):c.*438C>T	MEN1	Uncertain significance	criteria provided, single submitter
305304	NM_001370259.2(MEN1):c.*392G>A	MEN1	Uncertain significance	criteria provided, single submitter
305305	NM_001370259.2(MEN1):c.*373G>C	MEN1	Uncertain significance	criteria provided, single submitter
305309	NM_001370259.2(MEN1):c.*272T>C	MEN1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPV6	Orphanet:417	Neonatal severe primary hyperparathyroidism
TRPV6	Orphanet:676	Autosomal dominant hereditary chronic pancreatitis
CDC73	Orphanet:143	Parathyroid carcinoma
CDC73	Orphanet:99879	Familial isolated hyperparathyroidism
CDC73	Orphanet:99880	Hyperparathyroidism-jaw tumor syndrome
MEN1	Orphanet:2965	Prolactinoma
MEN1	Orphanet:314786	Silent pituitary adenoma
MEN1	Orphanet:314790	Null pituitary adenoma
MEN1	Orphanet:652	Multiple endocrine neoplasia type 1
MEN1	Orphanet:97279	Insulinoma
MEN1	Orphanet:99725	Pituitary gigantism
MEN1	Orphanet:99879	Familial isolated hyperparathyroidism

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPV6	HGNC:14006	ENSG00000165125	Q9H1D0	Transient receptor potential cation channel subfamily V member 6	clinvar
CDC73	HGNC:16783	ENSG00000134371	Q6P1J9	Parafibromin	clinvar
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV6	Transient receptor potential cation channel subfamily V member 6	Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine.
CDC73	Parafibromin	Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways.
MEN1	Menin	Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Ion channel	1	37.2×	0.053
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV6	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TRPV5/TRPV6
CDC73	Other/Unknown	no		Cdc73/Parafibromin, CDC73_C, Cdc73_N
MEN1	Other/Unknown	no		Menin

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
duodenum	1
pancreas	1
calcaneal tendon	1
colonic epithelium	1
sural nerve	1
granulocyte	1
lower esophagus mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV6	125	tissue_specific	marker	body of pancreas, pancreas, duodenum
CDC73	271	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEN1	5,226
CDC73	4,592
TRPV6	1,197

Intra-cohort edges

A	B	Sources
CDC73	MEN1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEN1	O00255	69
TRPV6	Q9H1D0	24
CDC73	Q6P1J9	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the beta-catenin:TCF transactivating complex	2	80.1×	0.003	CDC73, MEN1
TCF dependent signaling in response to WNT	2	78.5×	0.003	CDC73, MEN1
Signaling by WNT	2	74.6×	0.003	CDC73, MEN1
Protein ubiquitination	1	271.9×	0.027	CDC73
TRP channels	1	135.9×	0.027	TRPV6
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	122.8×	0.027	MEN1
RHO GTPases activate IQGAPs	1	115.3×	0.027	MEN1
Dengue virus activates/modulates innate and adaptive immune responses	1	112.0×	0.027	CDC73
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	102.9×	0.027	MEN1
RNA Polymerase II Transcription	2	15.0×	0.027	CDC73, MEN1
Post-translational protein modification	2	12.8×	0.027	CDC73, MEN1
Gene expression (Transcription)	2	11.9×	0.027	CDC73, MEN1
Formation of WDR5-containing histone-modifying complexes	1	88.5×	0.029	MEN1
Deactivation of the beta-catenin transactivating complex	1	77.7×	0.029	MEN1
Signaling by TGF-beta Receptor Complex	1	66.8×	0.029	MEN1
Formation of RNA Pol II elongation complex	1	64.5×	0.029	CDC73
RNA Polymerase II Transcription Elongation	1	64.5×	0.029	CDC73
E3 ubiquitin ligases ubiquitinate target proteins	1	64.5×	0.029	CDC73
Signaling by Hedgehog	1	61.4×	0.029	CDC73
Hedgehog ‘on’ state	1	52.9×	0.030	CDC73
Epigenetic regulation by WDR5-containing histone modifying complexes	1	51.4×	0.030	MEN1
Metabolism of proteins	2	8.2×	0.030	CDC73, MEN1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	48.8×	0.030	MEN1
RNA Polymerase II Pre-transcription Events	1	45.9×	0.031	CDC73
Signaling by TGFB family members	1	38.5×	0.034	MEN1
CHD1 and CHD2 subfamily	1	36.2×	0.034	CDC73
Signal Transduction	2	6.8×	0.034	CDC73, MEN1
Post-translational protein phosphorylation	1	33.4×	0.036	MEN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	28.8×	0.040	MEN1
Epigenetic regulation of gene expression	1	23.8×	0.047	MEN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
parathyroid hormone secretion	1	2808.7×	0.012	TRPV6
positive regulation of mRNA 3’-end processing	1	1123.5×	0.012	CDC73
endodermal cell fate commitment	1	936.2×	0.012	CDC73
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	702.2×	0.012	MEN1
T-helper 2 cell differentiation	1	624.1×	0.012	MEN1
negative regulation of cell population proliferation	2	28.1×	0.012	CDC73, MEN1
positive regulation of cell cycle G1/S phase transition	1	374.5×	0.014	CDC73
osteoblast development	1	330.4×	0.014	MEN1
regulation of calcium ion-dependent exocytosis	1	312.1×	0.014	TRPV6
negative regulation of myeloid cell differentiation	1	312.1×	0.014	CDC73
obsolete negative regulation of DNA-binding transcription factor activity	1	244.2×	0.014	MEN1
negative regulation of protein phosphorylation	1	193.7×	0.014	MEN1
response to gamma radiation	1	193.7×	0.014	MEN1
mRNA 3’-end processing	1	187.2×	0.014	CDC73
negative regulation of JNK cascade	1	187.2×	0.014	MEN1
calcium ion import across plasma membrane	1	181.2×	0.014	TRPV6
positive regulation of transforming growth factor beta receptor signaling pathway	1	175.5×	0.014	MEN1
negative regulation of fibroblast proliferation	1	165.2×	0.014	CDC73
transcription elongation by RNA polymerase II	1	147.8×	0.014	CDC73
calcium ion homeostasis	1	147.8×	0.014	TRPV6
stem cell population maintenance	1	140.4×	0.014	CDC73
positive regulation of Wnt signaling pathway	1	127.7×	0.014	CDC73
transcription initiation-coupled chromatin remodeling	1	127.7×	0.014	MEN1
response to UV	1	122.1×	0.014	MEN1
negative regulation of G1/S transition of mitotic cell cycle	1	119.5×	0.014	CDC73
response to calcium ion	1	106.0×	0.014	TRPV6
positive regulation of transcription elongation by RNA polymerase II	1	100.3×	0.014	CDC73
negative regulation of osteoblast differentiation	1	98.5×	0.014	MEN1
protein destabilization	1	96.8×	0.014	CDC73
negative regulation of cell cycle	1	96.8×	0.014	MEN1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Cholecalciferol	Phase 3 (in late-stage trials)
Cinacalcet	Phase 3 (in late-stage trials)
Paricalcitol	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 0

Druggability breadth: 3 of 3 evidence-associated genes (100%) 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
TRPV6	ECONAZOLE
MEN1	LOPERAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
TRPV6	3	4
CDC73	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ECONAZOLE	4	TRPV6
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MEN1	93	Binding:86, Functional:7
TRPV6	32	Binding:32
CDC73	8	Binding:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
ECONAZOLE	4	TRPV6
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TRPV6, MEN1
B	Phased (≥1) drug, not yet approved	1	CDC73
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 71.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	47
PHASE3	6
PHASE4	5
PHASE2	4
EARLY_PHASE1	3
PHASE1	3
PHASE2/PHASE3	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00037518	PHASE4	COMPLETED	A Study of an Investigational Medication for Severe Primary Hyperparathyroidism or Parathyroid Cancer
NCT00359385	PHASE4	WITHDRAWN	The Effects of Alendronate After Cure of Primary Hyperparathyroidism
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT01143987	PHASE4	COMPLETED	Cincalcet and Vascular Arterial Stiffness Among Peritoneal Dialysis Patients With Secondary Hyperparathyroidism
NCT01573520	PHASE4	COMPLETED	Treatment Adhesion in Dialysis Patients Treated With Cinacalcet
NCT00006329	PHASE2/PHASE3	COMPLETED	Comparison of Two Methods of Parathyroidectomy for Primary Hyperparathyroidism
NCT00417612	PHASE3	COMPLETED	Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets
NCT00527267	PHASE3	COMPLETED	Safety and Efficacy Study of AMG 073 in Hemodialysis Subjects
NCT00975000	PHASE3	COMPLETED	Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients
NCT01191762	PHASE3	COMPLETED	Sevelamer and Secondary Hyperparathyroidism in Chronic Kidney Disease
NCT01277510	PHASE3	TERMINATED	Pediatric Chronic Kidney Disease Safety and Efficacy
NCT02747979	PHASE2/PHASE3	COMPLETED	The Effect and Safety of Hemodialysis and Hemoperfusion on Severe Renal Osteopathy and Itching in Uremia Patients
NCT04040946	PHASE3	COMPLETED	Trial Comparing 2 Diagnostic Strategies for Preoperative Localization of Parathyroid Adenoma in Primary Hyperparathyroidism:TEMP / CT With Tc99m-sestaMIBI or PET / CT With F18-choline in First Intention
NCT00001277	PHASE2	COMPLETED	Studies of Elevated Parathyroid Activity
NCT00744302	PHASE2	COMPLETED	Study of 1.25 mmol/L Calcium Dialysate on Mineral Metabolism in Haemodialysis Patients.
NCT01656070	PHASE2	COMPLETED	Vitamin D Supplementation in HIV-infected Youth
NCT01935856	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of KHK7580 for Secondary Hyperparathyroidism in Patients Receiving Hemodialysis
NCT02432599	PHASE2	COMPLETED	Interest of the F18-choline as a Second Line of the Tracer for Detection of Parathyroid Adenomas
NCT00538720	PHASE1	COMPLETED	Effects of Vitamin D Replacement in Patients With Primary Hyperparathyroidism (PHPT)
NCT00573573	PHASE1	UNKNOWN	Energy Specific Far Infrared Radiation Treatment for Hyperparathyroidism
NCT01333267	PHASE1	WITHDRAWN	One Week Comparison Study of PTH and PTHrP Infusions
NCT00377312	EARLY_PHASE1	COMPLETED	7 Day Continuous Parathyroid Hormone IV Infusion
NCT00580788	EARLY_PHASE1	COMPLETED	One Week Parathyroid Hormone-related Protein (PTHrP) IV Dose Escalation Study
NCT02986607	EARLY_PHASE1	UNKNOWN	Corticosteroid Rhythms in Hypoparathyroid Patients
NCT00169806	Not specified	ACTIVE_NOT_RECRUITING	Randall’s Plaque Study: Pathogenesis and Relationship to Nephrolithiasis
NCT05667090	Not specified	RECRUITING	Effects of Multiple Mega-dose of Vitamin D3 Supplementation on Ameliorating Moderate to Severe Chronic Pain in Hemodialysis Patients
NCT05963841	Not specified	RECRUITING	NUclear MEdicine DIagnostic and Artificial Intelligence
NCT06499142	Not specified	ACTIVE_NOT_RECRUITING	STP.168 Clinical Study Protocol Parakeet
NCT06711874	Not specified	ACTIVE_NOT_RECRUITING	Abnormally High Parathyroid Hormone Levels Worsens Outcomes in Vitamin D Depleted Critical Care Patients
NCT06797934	Not specified	RECRUITING	Establishment of a Registry of Patients With Parathyroid Disease
NCT06852144	Not specified	ENROLLING_BY_INVITATION	PET-TC in Thyroid Evaluation
NCT07010380	Not specified	RECRUITING	Dual-Channel Near-Infrared Autofluorescence Imaging and AI Analysis to Locate Parathyroid Glands (PTFinder)
NCT07083557	Not specified	RECRUITING	Routine Validation and Reproducibility Testing of Laboratory Assays and Research Techniques Used for Endocrine, Cardiometabolic, and Musculoskeletal Disorder Research (VALD)
NCT07103876	Not specified	RECRUITING	Parathyroidectomy and Mobility Study
NCT07415421	Not specified	RECRUITING	Parathyroidectomy After Kidney Transplantation
NCT00004843	Not specified	COMPLETED	A Randomized Study of Surgery vs No Surgery in Patients With Mild Asymptomatic Primary Hyperparathyroidism
NCT00374595	Not specified	COMPLETED	Vascular Risk After Kidney Transplantation
NCT00395902	Not specified	COMPLETED	Post Transplant Study
NCT00452049	Not specified	UNKNOWN	The Effect of Parathyroidectomy on Renal Function, Endothelial Function, and Blood Pressure
NCT00501215	Not specified	COMPLETED	Effect of Parathyroidectomy on Sleep

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CINACALCET	4	12
CHOLECALCIFEROL	4	4
METHYLENE BLUE CATION	4	3
PARATHYROID HORMONE	4	3
LISINOPRIL ANHYDROUS	4	2
AMINOSALICYLIC ACID	4	1
EDOTREOTIDE GALLIUM GA-68	4	1
FLUORODOPA F 18	4	1
PARICALCITOL	4	1
RISEDRONIC ACID	4	1
SEVELAMER CARBONATE	4	1
EVOCALCET	3	1