Parathyroid gland adenoma

Summary

Parathyroid gland adenoma (MONDO:0006890) is a cancer (an umbrella term covering 5 Mondo subtypes) with 4 cohort genes (3 CIViC-evidence somatic drivers; 5 ClinVar predisposition records) and 24 clinical trials. Top therapeutic interventions include parathyroid hormone and tramadol.

At a glance

• Classification: Cancer
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 4
• ClinVar variants: 5
• Clinical trials: 24

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	parathyroid gland adenoma
Mondo ID	MONDO:0006890
EFO	EFO:1001087
DOID	DOID:7608
NCIT	C156757, C3916
SNOMED CT	128474007
UMLS	C0262587
MedGen	75502
MedDRA	10033940
Anatomy (UBERON)	UBERON:0001132
Is cancer (heuristic)	yes

Also known as: adenoma of parathyroid · adenoma of parathyroid gland · adenoma of the parathyroid · parathyroid adenoma · parathyroid gland adenoma

Data availability: 5 ClinVar variants · 1 HPO phenotype · 2 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › epithelial neoplasm › adenoma › parathyroid gland adenoma

Related subtypes (30): villous adenoma, breast adenoma, minor vestibular glands adenoma, cystadenoma, sebaceous adenoma, renal adenoma, prostatic adenoma, papillary adenoma, Bartholin gland adenoma, mixed cell adenoma, lung adenoma, middle ear adenoma, oncocytic adenoma, clear cell adenoma, lipoadenoma, water-clear cell adenoma, vaginal adenoma, microcystic adenoma, rete testis adenoma, adrenal cortex adenoma, follicular thyroid adenoma, ovarian adenoma benign, digestive system adenoma, mixed somatotroph-lactotroph pituitary gland adenoma, pituitary gland adenoma, hepatocellular adenoma, adenoma of pancreas, sweat gland adenoma, tubular adenoma, tubulovillous adenoma

Subtypes (5): chief cell adenoma, parathyroid gland clear cell adenoma, mixed cell type adenoma of parathyroid, parathyroid oncocytic adenoma, familial parathyroid adenoma

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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
374153	NM_000388.4(CASR):c.2449G>A (p.Val817Ile)	CASR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3278	NM_024529.5(CDC73):c.685_688del (p.Arg229fs)	CDC73	Pathogenic	criteria provided, single submitter
374107	NM_001370259.2(MEN1):c.654+1del	MEN1	Pathogenic	criteria provided, single submitter
523339	NM_001370259.2(MEN1):c.371_372del (p.Val124fs)	MEN1	Pathogenic	criteria provided, single submitter
1339457	NM_005343.4(HRAS):c.278T>C (p.Ile93Thr)	HRAS	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 19 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CDC73	Act	UCEC
HRAS	Act	ANGS,BLCA,BRCA,COADREAD,CSCC,HNSC,LUSC,NPC,PGNG,PRAD,PROSTATE,THYM,UTUC,WDTC	CIViC #2747
MEN1	LoF	ACC,BLCA,BRCA,HCC,LUNG,PANCREAS,PANET,WDTC	CIViC #3485

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CASR	Orphanet:417	Neonatal severe primary hyperparathyroidism
CASR	Orphanet:428	Autosomal dominant hypocalcemia
CASR	Orphanet:676	Autosomal dominant hereditary chronic pancreatitis
CASR	Orphanet:93372	Familial hypocalciuric hypercalcemia type 1
CDC73	Orphanet:143	Parathyroid carcinoma
CDC73	Orphanet:99879	Familial isolated hyperparathyroidism
CDC73	Orphanet:99880	Hyperparathyroidism-jaw tumor syndrome
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
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

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CASR	HGNC:1514	ENSG00000036828	P41180	Extracellular calcium-sensing receptor	clinvar
CDC73	HGNC:16783	ENSG00000134371	Q6P1J9	Parafibromin	clinvar
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	clinvar
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CASR	Extracellular calcium-sensing receptor	G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis.
CDC73	Parafibromin	Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
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: 2 · Difficult: 0 · Unknown: 2 · 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
GPCR	1	6.0×	0.441
Enzyme (other)	1	3.0×	0.441
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CASR	GPCR	yes		GPCR_3_Ca_sens_rcpt-rel, GPCR_3, ANF_lig-bd_rcpt
CDC73	Other/Unknown	no		Cdc73/Parafibromin, CDC73_C, Cdc73_N
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MEN1	Other/Unknown	no		Menin

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
diaphragm	1
hair follicle	1
islet of Langerhans	1
calcaneal tendon	1
colonic epithelium	1
sural nerve	1
skin of abdomen	1
skin of leg	1
zone of skin	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
CASR	63	tissue_specific	marker	islet of Langerhans, diaphragm, hair follicle
CDC73	271	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HRAS	8,064
MEN1	5,226
CDC73	4,592
CASR	2,692

Intra-cohort edges

A	B	Sources
CASR	CDC73	string_interaction
CASR	MEN1	string_interaction
CDC73	MEN1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HRAS	P01112	246
MEN1	O00255	69
CASR	P41180	31
CDC73	Q6P1J9	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 107. 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
Formation of the beta-catenin:TCF transactivating complex	2	60.1×	0.017	CDC73, MEN1
TCF dependent signaling in response to WNT	2	58.9×	0.017	CDC73, MEN1
Signaling by WNT	2	56.0×	0.017	CDC73, MEN1
Signaling by RAS GAP mutants	1	951.7×	0.018	HRAS
Signaling by RAS GTPase mutants	1	951.7×	0.018	HRAS
Activation of RAS in B cells	1	571.0×	0.018	HRAS
RAS signaling downstream of NF1 loss-of-function variants	1	407.9×	0.018	HRAS
Estrogen-stimulated signaling through PRKCZ	1	407.9×	0.018	HRAS
SOS-mediated signalling	1	356.9×	0.018	HRAS
Activated NTRK3 signals through RAS	1	317.2×	0.018	HRAS
EGFR Transactivation by Gastrin	1	285.5×	0.018	HRAS
SHC-related events triggered by IGF1R	1	285.5×	0.018	HRAS
Activated NTRK2 signals through RAS	1	285.5×	0.018	HRAS
MET activates RAS signaling	1	259.6×	0.018	HRAS
Signaling by FGFR4 in disease	1	237.9×	0.018	HRAS
Activated NTRK2 signals through FRS2 and FRS3	1	237.9×	0.018	HRAS
Constitutive Signaling by Overexpressed ERBB2	1	237.9×	0.018	HRAS
p38MAPK events	1	219.6×	0.018	HRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	219.6×	0.018	HRAS
Signaling by PDGFRA extracellular domain mutants	1	219.6×	0.018	HRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	203.9×	0.018	HRAS
Protein ubiquitination	1	203.9×	0.018	CDC73
GRB2 events in EGFR signaling	1	190.3×	0.018	HRAS
Erythropoietin activates RAS	1	190.3×	0.018	HRAS
Signaling by FLT3 ITD and TKD mutants	1	190.3×	0.018	HRAS
SHC1 events in ERBB4 signaling	1	178.4×	0.018	HRAS
SHC1 events in EGFR signaling	1	178.4×	0.018	HRAS
Constitutive Signaling by EGFRvIII	1	178.4×	0.018	HRAS
Signalling to RAS	1	167.9×	0.018	HRAS
Insulin receptor signalling cascade	1	167.9×	0.018	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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cell population proliferation	3	31.6×	0.005	CDC73, HRAS, MEN1
MAPK cascade	2	76.6×	0.013	HRAS, MEN1
regulation of presynaptic membrane potential	1	2106.5×	0.014	CASR
positive regulation of miRNA metabolic process	1	1404.3×	0.014	HRAS
chemosensory behavior	1	842.6×	0.014	CASR
positive regulation of mRNA 3’-end processing	1	842.6×	0.014	CDC73
bile acid secretion	1	842.6×	0.014	CASR
positive regulation of ERK1 and ERK2 cascade	2	42.6×	0.014	CASR, HRAS
positive regulation of transcription by RNA polymerase II	3	11.2×	0.014	CDC73, HRAS, MEN1
endodermal cell fate commitment	1	702.2×	0.015	CDC73
oncogene-induced cell senescence	1	601.9×	0.015	HRAS
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	526.6×	0.015	MEN1
response to fibroblast growth factor	1	526.6×	0.015	CASR
T-helper 1 type immune response	1	468.1×	0.015	HRAS
T-helper 2 cell differentiation	1	468.1×	0.015	MEN1
fat pad development	1	421.3×	0.015	CASR
cellular response to peptide	1	421.3×	0.015	CASR
cellular response to vitamin D	1	383.0×	0.015	CASR
positive regulation of positive chemotaxis	1	351.1×	0.016	CASR
detection of calcium ion	1	280.9×	0.016	CASR
cellular response to hepatocyte growth factor stimulus	1	280.9×	0.016	CASR
positive regulation of cell cycle G1/S phase transition	1	280.9×	0.016	CDC73
Schwann cell development	1	263.3×	0.016	HRAS
osteoblast development	1	247.8×	0.016	MEN1
regulation of long-term neuronal synaptic plasticity	1	247.8×	0.016	HRAS
positive regulation of ruffle assembly	1	247.8×	0.016	HRAS
negative regulation of myeloid cell differentiation	1	234.1×	0.016	CDC73
positive regulation of calcium ion import	1	234.1×	0.016	CASR
cellular response to low-density lipoprotein particle stimulus	1	221.7×	0.016	CASR
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	221.7×	0.016	HRAS

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 4 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
CASR	CINACALCET HYDROCHLORIDE
HRAS	LONAFARNIB
MEN1	LOPERAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
CASR	10	4
HRAS	4	4
CDC73	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CINACALCET HYDROCHLORIDE	4	CASR
CINACALCET	4	CASR
LONAFARNIB	4	HRAS
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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MEN1	93	Binding:86, Functional:7
HRAS	48	Binding:45, Functional:3
CASR	45	Functional:32, Binding:13
CDC73	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HRAS	3.6.5.2	small monomeric GTPase

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).

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
CINACALCET HYDROCHLORIDE	4	CASR
CINACALCET	4	CASR
LONAFARNIB	4	HRAS
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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CASR, HRAS, 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: 24.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	19
PHASE3	2
PHASE4	1
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03469310	PHASE4	COMPLETED	Minimizing Narcotic Analgesics After Endocrine Surgery
NCT05891769	PHASE2/PHASE3	RECRUITING	99mTc Sestamibi SPECT/CT vs 18F Fluorocholine PET/CT
NCT03027557	PHASE3	COMPLETED	Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.
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
NCT04085913	EARLY_PHASE1	ENROLLING_BY_INVITATION	Exparel Injection Effect on Postoperative Opioid Usage
NCT03039439	Not specified	RECRUITING	Molecular and Immunohistochemical Profiling of Tumors in Patients With Parathyroid Tumors
NCT06499142	Not specified	ACTIVE_NOT_RECRUITING	STP.168 Clinical Study Protocol Parakeet
NCT06835426	Not specified	RECRUITING	High-resolution PET-CT Specimen Imaging for the Perioperative Visualization of Resection Margins
NCT06913296	Not specified	RECRUITING	PTeye in Parathyroid Adenoma
NCT07043010	Not specified	NOT_YET_RECRUITING	WHITE CAP: Intra-operative Parathyroid Tissue Sensor (PTS)-Guided Assessment of Parathyroid Viability and Surgical Decision-Making
NCT07099404	Not specified	NOT_YET_RECRUITING	Parathyroid Adenoma Detection With Rubidium-82 Imaging
NCT07218224	Not specified	AVAILABLE	Expanded Access:18F-Fluorocholine for the Detection of Parathyroid Adenomas
NCT07595666	Not specified	ENROLLING_BY_INVITATION	Comparison of NeuroEXPLORER PET/CT Versus Standard-of-care PET/CT of the Head and Neck Region.
NCT01084356	Not specified	UNKNOWN	Evaluation of a New CZT System
NCT01291498	Not specified	TERMINATED	High Intensity Focused Ultrasound (HIFU) for Parathyroid Adenoma
NCT02381925	Not specified	WITHDRAWN	Multicenter Registry Comparing Preoperative Imaging for Primary Hyperparathyroidism
NCT03011736	Not specified	COMPLETED	Omission of Intact Parathyroid Hormone Testing During Surgery in Treating Patients With Primary Hyperparathyroidism
NCT03516747	Not specified	WITHDRAWN	Preoperational Fine Needle Aspiration of Pathological Parathyroid Gland
NCT04299425	Not specified	COMPLETED	Evaluating Impact of NIRAF Detection for Identifying Parathyroid Glands During Parathyroidectomy
NCT04344886	Not specified	COMPLETED	Optimization and Individualization of Diagnostic Scintigraphy Protocol and Minimally Invasive Radio-guided Parathyroid Surgery
NCT04570033	Not specified	COMPLETED	The Utility of 18F-fluorocholine PET/CT in the Imaging of Parathyroid Adenomas
NCT04905641	Not specified	COMPLETED	The Feasibility of Bilateral Intermediate Cervical Plexus Block for Thyroidectomy/Parathyroidectomy
NCT05022641	Not specified	COMPLETED	Evaluating Impact of Near Infrared Autofluorescence (NIRAF) Detection for Identifying Parathyroid Glands During Parathyroidectomy
NCT05152927	Not specified	COMPLETED	Near Infrared Autofluorescence (NIRAF) Detection for Identifying Parathyroid Glands During Parathyroidectomy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PARATHYROID HORMONE	4	1
TRAMADOL	4	1
CHEMBL4059722	0	1
(R,R)-TRAMADOL	0	1