Autosomal dominant hypocalcemia

Summary

Autosomal dominant hypocalcemia (MONDO:0018543) is a disease with 2 cohort genes and 56 clinical trials. Top therapeutic interventions include calcium gluconate, foscarnet, and calcium.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 10
• Phenotypes (HPO): 30
• Clinical trials: 56

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.161	Denmark	Validated
Point prevalence	1-9 / 100 000	3.9	United States	Validated

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0000708	Atypical behavior	Very frequent (80-99%)
HP:0000712	Emotional lability	Very frequent (80-99%)
HP:0000716	Depression	Very frequent (80-99%)
HP:0000739	Anxiety	Very frequent (80-99%)
HP:0002150	Hypercalciuria	Very frequent (80-99%)
HP:0002356	Writer’s cramp	Very frequent (80-99%)
HP:0002901	Hypocalcemia	Very frequent (80-99%)
HP:0003401	Paresthesia	Very frequent (80-99%)
HP:0003457	EMG abnormality	Very frequent (80-99%)
HP:0003473	Fatigable weakness	Very frequent (80-99%)
HP:0040148	Cortical myoclonus	Very frequent (80-99%)
HP:0000121	Nephrocalcinosis	Frequent (30-79%)
HP:0000958	Dry skin	Frequent (30-79%)
HP:0001231	Abnormal fingernail morphology	Frequent (30-79%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0001597	Abnormality of the nail	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002615	Hypotension	Frequent (30-79%)
HP:0002793	Abnormal pattern of respiration	Frequent (30-79%)
HP:0002905	Hyperphosphatemia	Frequent (30-79%)
HP:0002917	Hypomagnesemia	Frequent (30-79%)
HP:0011675	Arrhythmia	Frequent (30-79%)
HP:0012608	Hypermagnesiuria	Frequent (30-79%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000964	Eczematoid dermatitis	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0002516	Increased intracranial pressure	Occasional (5-29%)
HP:0004349	Reduced bone mineral density	Occasional (5-29%)
HP:0004372	Reduced consciousness/confusion	Occasional (5-29%)
HP:0007400	Irregular hyperpigmentation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant hypocalcemia
Mondo ID	MONDO:0018543
OMIM	601198
Orphanet	428
DOID	DOID:0090109
SNOMED CT	711152006
UMLS	C4048195
MedGen	884527
GARD	0002877
Is cancer (heuristic)	no

Also known as: AD hypocalcemia · hypocalcemia · hypocalcemia, autosomal dominant

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant hypocalcemia

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (2): autosomal dominant hypocalcemia 1, autosomal dominant hypocalcemia 2

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

10 retrieved; paginated sample, class counts are floors:

6 pathogenic, 3 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1397805	NM_000388.4(CASR):c.2008G>C (p.Gly670Arg)	CASR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1516739	NM_000388.4(CASR):c.2008G>A (p.Gly670Arg)	CASR	Pathogenic	criteria provided, multiple submitters, no conflicts
2203424	NM_000388.4(CASR):c.2440TTC[1] (p.Phe815del)	CASR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3068868	NM_000388.4(CASR):c.661C>T (p.Pro221Ser)	CASR	Pathogenic	criteria provided, single submitter
4525809	NM_000388.4(CASR):c.2361CTT[2] (p.Phe790del)	CASR	Pathogenic	criteria provided, multiple submitters, no conflicts
60667	NM_000388.4(CASR):c.662C>T (p.Pro221Leu)	CASR	Pathogenic	criteria provided, multiple submitters, no conflicts
8323	NM_000388.4(CASR):c.452C>T (p.Thr151Met)	CASR	Pathogenic	criteria provided, multiple submitters, no conflicts
8350	NM_000388.4(CASR):c.1810G>A (p.Glu604Lys)	CASR	Pathogenic	criteria provided, multiple submitters, no conflicts
959995	NM_000388.4(CASR):c.2299G>A (p.Glu767Lys)	CASR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
381654	NM_000388.4(CASR):c.2431A>G (p.Met811Val)	CASR	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 12 · 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
CASR	Definitive	Autosomal dominant	autosomal dominant hypocalcemia 1	11
GNA11	Strong	Autosomal dominant	autosomal dominant hypocalcemia 2	11

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
GNA11	Orphanet:101049	Familial hypocalciuric hypercalcemia type 2
GNA11	Orphanet:1556	Cutis marmorata telangiectatica congenita
GNA11	Orphanet:39044	Uveal melanoma
GNA11	Orphanet:428	Autosomal dominant hypocalcemia
GNA11	Orphanet:675359	Anastomosing haemangioma
GNA11	Orphanet:714737	Diffuse capillary malformation with overgrowth
GNA11	Orphanet:79483	Phakomatosis cesioflammea
GNA11	Orphanet:79484	Phakomatosis cesiomarmorata

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CASR	HGNC:1514	ENSG00000036828	P41180	Extracellular calcium-sensing receptor	gencc,clinvar
GNA11	HGNC:4379	ENSG00000088256	P29992	Guanine nucleotide-binding protein subunit alpha-11	gencc

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.
GNA11	Guanine nucleotide-binding protein subunit alpha-11	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · 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	12.0×	0.164
Other/Unknown	1	0.9×	0.805

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
GNA11	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
hair follicle	1
islet of Langerhans	1
ileal mucosa	1
jejunal mucosa	1
pancreatic ductal cell	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
GNA11	299	ubiquitous	marker	ileal mucosa, jejunal mucosa, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CASR	2,692
GNA11	1,873

Intra-cohort edges

A	B	Sources
CASR	GNA11	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CASR	P41180	31
GNA11	P29992	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
G alpha (q) signalling events	2	57.4×	0.005	CASR, GNA11
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	713.8×	0.010	GNA11
Acetylcholine regulates insulin secretion	1	571.0×	0.010	GNA11
G-protein activation	1	237.9×	0.012	GNA11
Thromboxane signalling through TP receptor	1	237.9×	0.012	GNA11
ADP signalling through P2Y purinoceptor 1	1	228.4×	0.012	GNA11
Thrombin signalling through proteinase activated receptors (PARs)	1	178.4×	0.012	GNA11
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	178.4×	0.012	GNA11
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	150.3×	0.012	GNA11
Class C/3 (Metabotropic glutamate/pheromone receptors)	1	146.4×	0.012	CASR
PLC beta mediated events	1	132.8×	0.012	GNA11
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	80.4×	0.018	GNA11
GPCR ligand binding	1	32.1×	0.040	CASR
GPCR downstream signalling	1	21.7×	0.054	CASR
Signaling by GPCR	1	20.0×	0.054	CASR
G alpha (i) signalling events	1	19.5×	0.054	CASR
Signal Transduction	1	5.1×	0.187	CASR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of insulin secretion	2	255.3×	7e-04	CASR, GNA11
phospholipase C-activating G protein-coupled receptor signaling pathway	2	131.7×	0.001	CASR, GNA11
regulation of melanocyte differentiation	1	8426.0×	0.002	GNA11
regulation of presynaptic membrane potential	1	4213.0×	0.003	CASR
chemosensory behavior	1	1685.2×	0.004	CASR
bile acid secretion	1	1685.2×	0.004	CASR
entrainment of circadian clock	1	1404.3×	0.004	GNA11
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	1	1053.2×	0.004	GNA11
developmental pigmentation	1	1053.2×	0.004	GNA11
phospholipase C-activating dopamine receptor signaling pathway	1	1053.2×	0.004	GNA11
cellular response to pH	1	1053.2×	0.004	GNA11
response to fibroblast growth factor	1	1053.2×	0.004	CASR
ligand-gated ion channel signaling pathway	1	936.2×	0.004	GNA11
fat pad development	1	842.6×	0.004	CASR
endothelin receptor signaling pathway	1	842.6×	0.004	GNA11
cellular response to peptide	1	842.6×	0.004	CASR
cellular response to vitamin D	1	766.0×	0.004	CASR
positive regulation of positive chemotaxis	1	702.2×	0.004	CASR
phototransduction, visible light	1	648.1×	0.004	GNA11
detection of calcium ion	1	561.7×	0.004	CASR
cellular response to hepatocyte growth factor stimulus	1	561.7×	0.004	CASR
G protein-coupled acetylcholine receptor signaling pathway	1	526.6×	0.004	GNA11
positive regulation of calcium ion import	1	468.1×	0.004	CASR
cranial skeletal system development	1	468.1×	0.004	GNA11
cellular response to low-density lipoprotein particle stimulus	1	443.5×	0.004	CASR
regulation of calcium ion transport	1	401.2×	0.005	CASR
branching morphogenesis of an epithelial tube	1	366.4×	0.005	CASR
positive regulation of vasoconstriction	1	300.9×	0.006	CASR
positive regulation of NLRP3 inflammasome complex assembly	1	290.6×	0.006	CASR
vasodilation	1	183.2×	0.009	CASR

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CASR	10	4
GNA11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CINACALCET HYDROCHLORIDE	4	CASR
CINACALCET	4	CASR
ENCALERET	3	CASR
EVOCALCET	3	CASR
SB-423562	2	CASR
RONACALERET	2	CASR
TECALCET HYDROCHLORIDE	2	CASR
FENDILINE	2	CASR
TECALCET	2	CASR
ATF-936	1	CASR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CASR	45	Functional:32, Binding:13
GNA11	18	Binding:18

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

8 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)
CINACALCET HYDROCHLORIDE	4	CASR
CINACALCET	4	CASR
EVOCALCET	3	CASR
RONACALERET	2	CASR
TECALCET HYDROCHLORIDE	2	CASR
FENDILINE	2	CASR
TECALCET	2	CASR
ATF-936	1	CASR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CASR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GNA11

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GNA11	18	CASR

Clinical trials & evidence

Clinical trials

Clinical trials: 56.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	33
PHASE2	9
PHASE4	7
PHASE3	4
PHASE2/PHASE3	1
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00002146	PHASE4	COMPLETED	Safety and Efficacy of Intravenous Magnesium Sulfate in Modulating Changes in Symptoms and Divalent Cation Levels Associated With Foscavir Therapy: A Phase IV Randomized, Double-Blind, Placebo-Controlled, Cross-Over, Pilot Study
NCT00668200	PHASE4	COMPLETED	Impact on Reducing the Incidence of Low Serum Calcium by Providing Educational Materials on the Need to Take Daily Supplemental Calcium and Vitamin D to Patients With Paget’s Disease Treated With Reclast®
NCT01632514	PHASE4	UNKNOWN	Vitamin D Deficiency and Postoperative Hypocalcemia
NCT04012476	PHASE4	UNKNOWN	Determination of Parathyroid Function by Fluorescence With Indocyanine Green (ICG) After Total Thyroidectomy
NCT04412694	PHASE4	UNKNOWN	The Effect of Preoperative Oral Dexamethasone Supplementation on the Outcome of Thyroidectomised Patients.
NCT04491357	PHASE4	UNKNOWN	Prophylactic Infusion of Calcium Gluconate Reducing the Rate of Hypocalcaemia After Total Thyroidectomy
NCT05216419	PHASE4	COMPLETED	Prevention of Postoperative Hypocalcemia of Oral Vitamin D Supplementation Before Total Thyroidectomy
NCT04775381	PHASE3	RECRUITING	Total Post-thyroidectomy Hypocalcemia After Preoperative Cholecalciferol Supplementation
NCT05680818	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1
NCT06820645	PHASE2/PHASE3	NOT_YET_RECRUITING	Calcium Administration in Life-saving Management During Massive Hemorrhage
NCT04750460	PHASE3	COMPLETED	Injection of Teriparatide to Prevent Hypocalcemia After Parathyroidectomy in Dialysis Patients (TeriCa).
NCT05953376	PHASE3	WITHDRAWN	Empiric Calcium in Massive Transfusion
NCT05732883	PHASE2	RECRUITING	The Use of Dexamethasone in Total Thyroidectomy to Improve Voice Outcome and Hypocalcaemia
NCT00001151	PHASE2	TERMINATED	Studies With 1,25-Dihydroxycholecalciferol
NCT00053378	PHASE2	COMPLETED	A Study to Examine the Use of Zemplar to Increase Serum Calcium Levels in ICU Subjects
NCT00623974	PHASE2	TERMINATED	Teriparatide (Forteo) in the Treatment of Patients With Postoperative Hypocalcemia
NCT00630214	PHASE2	COMPLETED	Prevention of Hypocalcemia in Patients Undergoing Total Thyroidectomy Plus Central Neck Dissection
NCT00743782	PHASE2	COMPLETED	Comparing Pump With Subcutaneous Injection Delivery of PTH 1-34 in the Management of Chronic Hypoparathyroidism
NCT01868750	PHASE2	COMPLETED	Phase II Pre-operative Vitamin D Supplementation to Prevent Post-thyroidectomy Hypocalcemia
NCT02204579	PHASE2	COMPLETED	A Study to Determine the Effects of NPSP795 on the Calcium-sensing Receptor in Subjects With Autosomal Dominant Hypocalcemia as Measured by PTH Levels and Blood Calcium Concentrations
NCT04581629	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1
NCT02274623	PHASE1	COMPLETED	Effect of CTAP101 Capsules on Ca/iPTH in Advanced Breast/Prostate Cancer Patients Treated With Denosumab/Zoledronic Acid
NCT05973747	EARLY_PHASE1	COMPLETED	Pharmacokinetic Equivalence of Calcium Gluconate and Calcium Chloride in Parturients
NCT05227287	Not specified	ACTIVE_NOT_RECRUITING	ADH1 and ADH2 Disease Monitoring Study (DMS)
NCT05585593	Not specified	RECRUITING	Registry for Hypoparathyroidism Wuerzburg
NCT05885256	Not specified	ACTIVE_NOT_RECRUITING	Clinical Assessment of Low Calcium In traUMa (CALCIUM)
NCT06763549	Not specified	ENROLLING_BY_INVITATION	COR-INSIGHT: Optimizing Cardiovascular and Cardiopulmonary Outcomes with AI-Driven Multiplexed Indications Using COR ECG Wearable
NCT06775288	Not specified	ACTIVE_NOT_RECRUITING	Hypoglycemia Prevention and Awareness Program
NCT07043010	Not specified	NOT_YET_RECRUITING	WHITE CAP: Intra-operative Parathyroid Tissue Sensor (PTS)-Guided Assessment of Parathyroid Viability and Surgical Decision-Making
NCT07416149	Not specified	RECRUITING	Comparing PTeye-assisted Versus Conventional Total Thyroidectomy
NCT07428057	Not specified	RECRUITING	Postoperative Hypocalcemia After Thyroidectomy
NCT00001242	Not specified	COMPLETED	Studies of States With Resistance to Vitamin D and Parathyroid Hormone
NCT00506103	Not specified	COMPLETED	The No-Tie Technique Using the Harmonic Scalpel in Total Thyroidectomy With Central Neck Dissection: A Prospective Randomized Study
NCT00601328	Not specified	COMPLETED	Bioequivalency Study of Calcitriol Tablets Under Fasting Conditions
NCT01021280	Not specified	UNKNOWN	Parathyroid Hormone (PTH) Homeostasis in Bartter Syndrome
NCT01039714	Not specified	UNKNOWN	Vitamin D Levels and Postoperative Hypocalcemia After Total Thyroidectomy
NCT01609439	Not specified	WITHDRAWN	Preoperative Vitamin D for Post-thyroidectomy Hypocalcemia
NCT01638494	Not specified	COMPLETED	Calcium and Vitamin D Intakes in Children
NCT02853721	Not specified	COMPLETED	Early Prediction of Hypocalcaemia Following Thyroid Surgery
NCT02889952	Not specified	COMPLETED	Clinical Impact of Parathyroid Autofluorescence Visualization During Thyroid Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CALCIUM GLUCONATE	4	4
FOSCARNET	4	4
CALCIUM	4	3
CALCITRIOL	4	2
CHOLECALCIFEROL	4	2
INDOCYANINE GREEN ACID FORM	4	2
TERIPARATIDE	4	2
CALCIFEDIOL	4	1
CALCIUM CARBONATE	4	1
CALCIUM CHLORIDE	4	1
ERGOCALCIFEROL	4	1
MAGNESIUM SULFATE	4	1
ZOLEDRONIC ACID	4	1
ENCALERET	3	2
SB-423562	2	1
CHEMBL5072826	0	3