Tubular aggregate myopathy

Summary

Tubular aggregate myopathy (MONDO:0008051) is a disease caused by ORAI1 (GenCC Strong), with 7 cohort genes. The dominant Reactome pathway is Ion homeostasis (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ORAI1 (GenCC Strong)
• Cohort genes: 7
• ClinVar variants: 781
• Phenotypes (HPO): 9

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		60	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0003326	Myalgia	Very frequent (80-99%)
HP:0003394	Muscle spasm	Very frequent (80-99%)
HP:0003458	EMG: myopathic abnormalities	Very frequent (80-99%)
HP:0003473	Fatigable weakness	Very frequent (80-99%)
HP:0030200	Fatiguable weakness of proximal limb muscles	Very frequent (80-99%)
HP:0100301	Muscle fiber tubular inclusions	Very frequent (80-99%)
HP:0003557	Increased variability in muscle fiber diameter	Frequent (30-79%)
HP:0003687	Centrally nucleated skeletal muscle fibers	Frequent (30-79%)
HP:0003554	Type 2 muscle fiber atrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	tubular aggregate myopathy
Mondo ID	MONDO:0008051
OMIM	160565
Orphanet	2593
DOID	DOID:0080089
UMLS	C0410207
MedGen	98050
GARD	0003884
Is cancer (heuristic)	no

Also known as: myopathy, tubular aggregate, 1 · myopathy, tubular aggregate, type 1 · TAM1 · tubular aggregate myopathy

Data availability: 781 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › tubular aggregate myopathy

Related subtypes (53): Ullrich congenital muscular dystrophy, congenital structural myopathy, Bethlem myopathy, MYH7-related skeletal myopathy, cylindrical spirals myopathy, congenital myopathy 7A, myosin storage, autosomal dominant, intellectual disability-myopathy-short stature-endocrine defect syndrome, myopathy, myosin storage, autosomal recessive, Bailey-Bloch congenital myopathy, fingerprint body myopathy, myopathy, proximal, and ophthalmoplegia, Compton-North congenital myopathy, MEGF10-related myopathy, fetal akinesia-cerebral and retinal hemorrhage syndrome, Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome, myopathy with hexagonally cross-linked tubular arrays, benign Samaritan congenital myopathy, congenital generalized hypercontractile muscle stiffness syndrome, hyaline body myopathy, centronuclear myopathy, reducing body myopathy, myopathy, congenital, with tremor, myopathy, congenital, progressive, with scoliosis, myopathy, congenital, with structured cores and z-line abnormalities, myopathy, congenital, with respiratory insufficiency and bone fractures, myopathy, congenital proximal, with minicore lesions, myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, congenital myopathy with reduced type 2 muscle fibers, alpha-actinopathy, SELENON-related myopathy, TPM3-related myopathy, SCN4A-related myopathy, autosomal recessive, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, Batten-Turner congenital myopathy, TOR1AIP1-related myopathy, congenital myopathy 11, congenital myopathy 15, congenital myopathy 18, congenital myopathy 10b, mild variant, congenital myopathy 2b, severe infantile, autosomal recessive, congenital myopathy 2c, severe infantile, autosomal dominant, congenital myopathy 20, congenital myopathy 21 with early respiratory failure, congenital myopathy 22A, classic, congenital myopathy 22B, severe fetal, congenital myopathy 25, congenital myopathy 26, congenital myopathy 27, congenital myopathy 28 with rigid spine, congenital myopathy 29 with contractures

Subtypes (2): myopathy, tubular aggregate, 2, myopathy, tubular aggregate, 1

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

600 retrieved; paginated sample, class counts are floors:

296 uncertain significance, 245 likely benign, 16 pathogenic, 11 benign, 10 benign/likely benign, 9 likely pathogenic, 9 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3233253	NM_001231.5(CASQ1):c.166A>T (p.Asn56Tyr)	CASQ1	Pathogenic	criteria provided, single submitter
3233256	NM_001382.4(DPAGT1):c.1133A>T (p.Asn378Ile)	DPAGT1	Pathogenic	criteria provided, single submitter
189256	NM_032790.4(ORAI1):c.292G>A (p.Gly98Ser)	LOC130008987	Pathogenic	criteria provided, single submitter
132887	NM_001382567.1(STIM1):c.910C>T (p.Arg304Trp)	STIM1	Pathogenic	criteria provided, multiple submitters, no conflicts
1365102	NM_001382567.1(STIM1):c.869_887del (p.Ile290fs)	STIM1	Pathogenic	criteria provided, single submitter
1371047	NC_000011.9:g.(?3988762)(4113028_?)del	STIM1	Pathogenic	criteria provided, single submitter
1395833	NM_001382567.1(STIM1):c.262A>G (p.Ser88Gly)	STIM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143191	NM_001382567.1(STIM1):c.343A>T (p.Ile115Phe)	STIM1	Pathogenic	criteria provided, single submitter
1452705	NM_001382567.1(STIM1):c.163_164del (p.Leu55fs)	STIM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457776	NM_001382567.1(STIM1):c.1189del (p.Ala397fs)	STIM1	Pathogenic	criteria provided, single submitter
1459002	NC_000011.9:g.(?4076736)(4076887_?)del	STIM1	Pathogenic	criteria provided, single submitter
2928208	NM_001382567.1(STIM1):c.1463T>A (p.Leu488Ter)	STIM1	Pathogenic	criteria provided, single submitter
3752806	NM_001382567.1(STIM1):c.757C>T (p.Arg253Ter)	STIM1	Pathogenic	criteria provided, single submitter
3755531	NM_001382567.1(STIM1):c.30G>A (p.Trp10Ter)	STIM1	Pathogenic	criteria provided, single submitter
3756856	NM_001382567.1(STIM1):c.1437_1444dup (p.Glu482fs)	STIM1	Pathogenic	criteria provided, single submitter
3763455	NM_001382567.1(STIM1):c.325C>T (p.His109Tyr)	STIM1	Pathogenic	criteria provided, single submitter
41464	NM_001382567.1(STIM1):c.1285C>T (p.Arg429Cys)	STIM1	Pathogenic	criteria provided, single submitter
41481	NM_001382567.1(STIM1):c.251A>G (p.Asp84Gly)	STIM1	Pathogenic	criteria provided, single submitter
41483	NM_001382567.1(STIM1):c.326A>G (p.His109Arg)	STIM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4532276	NM_001382567.1(STIM1):c.148C>T (p.Arg50Ter)	STIM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3233259	NM_004837.4(GGPS1):c.770T>G (p.Phe257Cys)	GGPS1	Likely pathogenic	criteria provided, single submitter
1476711	NM_001382567.1(STIM1):c.386-1G>A	STIM1	Likely pathogenic	criteria provided, single submitter
189363	NM_001382567.1(STIM1):c.239A>C (p.Asn80Thr)	STIM1	Likely pathogenic	criteria provided, single submitter
2020521	NM_001382567.1(STIM1):c.270+2T>C	STIM1	Likely pathogenic	criteria provided, single submitter
2090235	NM_001382567.1(STIM1):c.1568-1G>T	STIM1	Likely pathogenic	criteria provided, single submitter
2091216	NM_001382567.1(STIM1):c.792-1G>A	STIM1	Likely pathogenic	criteria provided, single submitter
2424636	NC_000011.9:g.(?4045083)(4045237_?)dup	STIM1	Likely pathogenic	criteria provided, single submitter
3759326	NM_001382567.1(STIM1):c.270+1_270+2insCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAAAGTGATGAGG	STIM1	Likely pathogenic	criteria provided, single submitter
4785692	NM_001382567.1(STIM1):c.270+1G>C	STIM1	Likely pathogenic	criteria provided, single submitter
3233252	NM_001231.5(CASQ1):c.308G>A (p.Gly103Asp)	CASQ1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 17 · 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
STIM1	Definitive	Autosomal dominant	myopathy, tubular aggregate, 1	11
CASQ1	Strong	Autosomal dominant	myopathy due to calsequestrin and SERCA1 protein overload	3
ORAI1	Strong	Autosomal dominant	myopathy, tubular aggregate, 2	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STIM1	Orphanet:2593	Tubular aggregate myopathy
STIM1	Orphanet:317430	Combined immunodeficiency due to STIM1 deficiency
STIM1	Orphanet:3204	Stormorken-Sjaastad-Langslet syndrome
CASQ1	Orphanet:2593	Tubular aggregate myopathy
CASQ1	Orphanet:88635	Vacuolar myopathy with sarcoplasmic reticulum protein aggregates
ORAI1	Orphanet:2593	Tubular aggregate myopathy
ORAI1	Orphanet:317428	Combined immunodeficiency due to ORAI1 deficiency
ORAI1	Orphanet:3204	Stormorken-Sjaastad-Langslet syndrome
CAV3	Orphanet:101016	Romano-Ward syndrome
CAV3	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
CAV3	Orphanet:488650	Distal myopathy, Tateyama type
CAV3	Orphanet:97238	Rippling muscle disease
PGAP2	Orphanet:247262	Hyperphosphatasia-intellectual disability syndrome
DPAGT1	Orphanet:353327	Congenital myasthenic syndrome with glycosylation defect
DPAGT1	Orphanet:86309	DPAGT1-CDG
GGPS1	Orphanet:642945	Perrault syndrome type 1
GGPS1	Orphanet:642976	Perrault syndrome type 2

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STIM1	HGNC:11386	ENSG00000167323	Q13586	Stromal interaction molecule 1	gencc,clinvar
CASQ1	HGNC:1512	ENSG00000143318	P31415	Calsequestrin-1	gencc,clinvar
ORAI1	HGNC:25896	ENSG00000276045	Q96D31	Calcium release-activated calcium channel protein 1	gencc
CAV3	HGNC:1529	ENSG00000182533	P56539	Caveolin-3	clinvar
PGAP2	HGNC:17893	ENSG00000148985	Q9UHJ9	Acyltransferase PGAP2	clinvar
DPAGT1	HGNC:2995	ENSG00000172269	Q9H3H5	UDP-N-acetylglucosamine–dolichyl-phosphate N-acetylglucosaminephosphotransferase	clinvar
GGPS1	HGNC:4249	ENSG00000152904	O95749	Geranylgeranyl pyrophosphate synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STIM1	Stromal interaction molecule 1	Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels.
CASQ1	Calsequestrin-1	Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.
ORAI1	Calcium release-activated calcium channel protein 1	Pore-forming subunit of two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels.
CAV3	Caveolin-3	May act as a scaffolding protein within caveolar membranes.
PGAP2	Acyltransferase PGAP2	Involved in the fatty acid remodeling steps of GPI-anchor maturation where the unsaturated acyl chain at sn-2 of inositol phosphate is replaced by a saturated stearoyl chain.
DPAGT1	UDP-N-acetylglucosamine–dolichyl-phosphate N-acetylglucosaminephosphotransferase	UDP-N-acetylglucosamine–dolichyl-phosphate N-acetylglucosaminephosphotransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
GGPS1	Geranylgeranyl pyrophosphate synthase	Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.29

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
Enzyme (other)	2	3.4×	0.220
Other/Unknown	5	1.3×	0.332

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STIM1	Other/Unknown	no		SAM, SAM/pointed_sf, SOAR_STIM1/2
CASQ1	Other/Unknown	no		Calsequestrin, Calsequestrin_CS, Thioredoxin-like_sf
ORAI1	Other/Unknown	no		CRAC_channel, Orai_sf
CAV3	Other/Unknown	no		Caveolin, Caveolin_CS
PGAP2	Other/Unknown	no		CWH43_N, PGAP2
DPAGT1	Enzyme (other)	yes	2.7.8.15	Glycosyl_transferase_4, GPT, DPAGT1_ins
GGPS1	Enzyme (other)	yes	2.5.1.29	Polyprenyl_synt, Isoprenoid_synthase_dom_sf, Polyprenyl_synt_CS

Expression context

Cohort genes with no expression data: 0.

5 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	4
gastrocnemius	1
muscle of leg	1
gluteal muscle	1
skeletal muscle tissue of rectus abdominis	1
granulocyte	1
skin of leg	1
triceps brachii	1
vastus lateralis	1
corpus epididymis	1
lower esophagus mucosa	1
skin of abdomen	1
body of pancreas	1
mucosa of transverse colon	1
right adrenal gland	1
cortical plate	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STIM1	237	ubiquitous	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
CASQ1	195	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, gluteal muscle
ORAI1	177	ubiquitous	yes	granulocyte, hindlimb stylopod muscle, skin of leg
CAV3	157	tissue_specific	yes	hindlimb stylopod muscle, vastus lateralis, triceps brachii
PGAP2	280	ubiquitous	marker	corpus epididymis, lower esophagus mucosa, skin of abdomen
DPAGT1	271	ubiquitous	marker	mucosa of transverse colon, body of pancreas, right adrenal gland
GGPS1	298	ubiquitous	marker	sperm, male germ cell, cortical plate

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STIM1	3,074
GGPS1	2,519
CAV3	2,369
DPAGT1	1,928
CASQ1	1,601
ORAI1	1,239
PGAP2	887

Intra-cohort edges

A	B	Sources
ORAI1	STIM1	intact, string_interaction

Structural data

PDB: 5 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GGPS1	O95749	9
DPAGT1	Q9H3H5	8
STIM1	Q13586	6
CASQ1	P31415	6
ORAI1	Q96D31	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PGAP2	Q9UHJ9	90.00
CAV3	P56539	88.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 7 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ion homeostasis	3	102.0×	4e-05	STIM1, CASQ1, ORAI1
Elevation of cytosolic Ca2+ levels	2	237.9×	3e-04	STIM1, ORAI1
Muscle contraction	3	38.6×	3e-04	STIM1, CASQ1, CAV3
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	2	119.0×	5e-04	STIM1, ORAI1
Defective DPAGT1 causes CDG-1j, CMSTA2	1	951.7×	0.004	DPAGT1
Cardiac conduction	2	36.2×	0.004	STIM1, CASQ1
Lanosterol biosynthesis	1	126.9×	0.020	GGPS1
Platelet calcium homeostasis	1	119.0×	0.020	STIM1
Signaling by the B Cell Receptor (BCR)	1	57.7×	0.036	STIM1
Platelet homeostasis	1	46.4×	0.036	STIM1
Smooth Muscle Contraction	1	44.3×	0.036	CAV3
Activation of gene expression by SREBF (SREBP)	1	43.3×	0.036	GGPS1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	34.6×	0.042	DPAGT1
Stimuli-sensing channels	1	22.7×	0.059	CASQ1
Ion channel transport	1	16.0×	0.077	CASQ1
Hemostasis	1	6.0×	0.185	STIM1
Adaptive Immune System	1	5.0×	0.207	STIM1
Transport of small molecules	1	4.2×	0.228	CASQ1
Immune System	1	2.2×	0.382	STIM1

GO biological processes by enrichment

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

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of adenylate cyclase activity	2	963.0×	1e-04	STIM1, ORAI1
store-operated calcium entry	2	481.5×	3e-04	STIM1, ORAI1
regulation of store-operated calcium entry	2	300.9×	6e-04	STIM1, CASQ1
regulation of calcium ion transport	2	229.3×	8e-04	STIM1, ORAI1
geranylgeranyl diphosphate biosynthetic process	1	2407.4×	0.004	GGPS1
regulation of signal transduction by receptor internalization	1	2407.4×	0.004	CAV3
regulation of nerve growth factor receptor activity	1	2407.4×	0.004	CAV3
negative regulation of sarcomere organization	1	2407.4×	0.004	CAV3
negative regulation of membrane depolarization during cardiac muscle cell action potential	1	2407.4×	0.004	CAV3
positive regulation of store-operated calcium channel activity	1	2407.4×	0.004	CASQ1
geranyl diphosphate biosynthetic process	1	1203.7×	0.007	GGPS1
trans, trans-farnesyl diphosphate biosynthetic process	1	1203.7×	0.007	GGPS1
regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	1	601.9×	0.010	CASQ1
nucleus localization	1	601.9×	0.010	CAV3
regulation of membrane depolarization during cardiac muscle cell action potential	1	601.9×	0.010	CAV3
positive regulation of caveolin-mediated endocytosis	1	601.9×	0.010	CAV3
isoprenoid metabolic process	1	481.5×	0.010	GGPS1
membrane raft organization	1	481.5×	0.010	CAV3
activation of store-operated calcium channel activity	1	481.5×	0.010	STIM1
regulation of branching involved in mammary gland duct morphogenesis	1	481.5×	0.010	CAV3
regulation of skeletal muscle contraction	1	401.2×	0.010	CAV3
T-tubule organization	1	401.2×	0.010	CAV3
regulation of ventricular cardiac muscle cell membrane depolarization	1	401.2×	0.010	CAV3
cellular response to ionomycin	1	401.2×	0.010	CAV3
response to denervation involved in regulation of muscle adaptation	1	343.9×	0.010	CASQ1
detection of muscle stretch	1	343.9×	0.010	CAV3
regulation of p38MAPK cascade	1	343.9×	0.010	CAV3
caveola assembly	1	300.9×	0.011	CAV3
regulation of calcium ion import	1	300.9×	0.011	CAV3
mammary gland epithelium development	1	267.5×	0.011	ORAI1

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
STIM1	TERIFLUNOMIDE
ORAI1	MIBEFRADIL
GGPS1	MINODRONIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ORAI1	5	4
GGPS1	4	4
STIM1	2	4
CASQ1	0	0
CAV3	0	0
PGAP2	0	0
DPAGT1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TERIFLUNOMIDE	4	ORAI1, STIM1
MIBEFRADIL	4	ORAI1
ECONAZOLE	4	ORAI1
MICONAZOLE	4	ORAI1
MINODRONIC ACID	4	GGPS1
ZOLEDRONIC ACID	4	GGPS1
IBANDRONIC ACID	4	GGPS1
ZEGOCRACTIN	2	ORAI1, STIM1
SQ109	2	GGPS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
GGPS1	129	Binding:128, ADMET:1
ORAI1	59	Binding:57, Functional:1, ADMET:1
STIM1	35	Binding:33, Functional:1, ADMET:1
DPAGT1	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DPAGT1	2.7.8.15	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
GGPS1	2.5.1.29	geranylgeranyl diphosphate synthase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GGPS1	129

Pharmacogenomics

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

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

Chemical tractability of cohort targets

9 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)
TERIFLUNOMIDE	4	ORAI1, STIM1
MIBEFRADIL	4	ORAI1
ECONAZOLE	4	ORAI1
MICONAZOLE	4	ORAI1
MINODRONIC ACID	4	GGPS1
ZOLEDRONIC ACID	4	GGPS1
IBANDRONIC ACID	4	GGPS1
ZEGOCRACTIN	2	ORAI1, STIM1
SQ109	2	GGPS1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	STIM1, ORAI1, GGPS1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	DPAGT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	CASQ1, CAV3, PGAP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CASQ1	0	—
CAV3	0	—
PGAP2	0	—
DPAGT1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.