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Atlas / Disease / Thyrotoxic periodic paralysis

Thyrotoxic periodic paralysis

disease
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Also known as thyrotoxic hypokalemic periodic paralysis

Summary

Thyrotoxic periodic paralysis (MONDO:0019201) is a disease with 13 cohort genes (80 GWAS associations across 6 studies) and 2 clinical trials. The dominant Reactome pathway is Interferon gamma signaling (4 cohort genes).

At a glance

  • Prevalence: <1 / 1 000 000 (Europe)
  • Cohort genes: 13
  • GWAS associations: 80
  • Phenotypes (HPO): 42
  • Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Point prevalence<1 / 1 000 000EuropeNot yet validated

Signs & symptoms

Clinical features (HPO)

42 HPO clinical features (Orphanet curated; top 42 by frequency):

HPO IDTermFrequency
HP:0000836HyperthyroidismObligate (100%)
HP:0008153Periodic hypokalemic paresisObligate (100%)
HP:0012726Episodic hypokalemiaObligate (100%)
HP:0000975HyperhidrosisVery frequent (80-99%)
HP:0001513ObesityVery frequent (80-99%)
HP:0001962PalpitationsVery frequent (80-99%)
HP:0002445TetraplegiaVery frequent (80-99%)
HP:0002917HypomagnesemiaVery frequent (80-99%)
HP:0003457EMG abnormalityVery frequent (80-99%)
HP:0003470ParalysisVery frequent (80-99%)
HP:0003752Episodic flaccid weaknessVery frequent (80-99%)
HP:0004303Abnormal muscle fiber morphologyVery frequent (80-99%)
HP:0007340Lower limb muscle weaknessVery frequent (80-99%)
HP:0008180Mildly elevated creatine kinaseVery frequent (80-99%)
HP:0008285Transient hypophosphatemiaVery frequent (80-99%)
HP:0011784Thyrotoxicosis with diffuse goiterVery frequent (80-99%)
HP:0011785Thyrotoxicosis with toxic multinodular goitreVery frequent (80-99%)
HP:0011786Thyrotoxicosis with toxic single thyroid noduleVery frequent (80-99%)
HP:0012240Increased intramyocellular lipid dropletsVery frequent (80-99%)
HP:0012364Decreased urinary potassiumVery frequent (80-99%)
HP:0100647Graves diseaseVery frequent (80-99%)
HP:0002019ConstipationFrequent (30-79%)
HP:0003201RhabdomyolysisFrequent (30-79%)
HP:0003394Muscle spasmFrequent (30-79%)
HP:0003552Muscle stiffnessFrequent (30-79%)
HP:0009020Exercise-induced muscle fatigueFrequent (30-79%)
HP:0011998Postprandial hyperglycemiaFrequent (30-79%)
HP:0000016Urinary retentionFrequent (30-79%)
HP:0001265HyporeflexiaFrequent (30-79%)
HP:0001337TremorFrequent (30-79%)
HP:0001824Weight lossFrequent (30-79%)
HP:0001657Prolonged QT intervalOccasional (5-29%)
HP:0001663Ventricular fibrillationOccasional (5-29%)
HP:0003694Late-onset proximal muscle weaknessOccasional (5-29%)
HP:0005165Shortened PR intervalOccasional (5-29%)
HP:0011706Second degree atrioventricular blockOccasional (5-29%)
HP:0002486MyotoniaExcluded (0%)
HP:0003134Abnormality of peripheral nerve conductionExcluded (0%)
HP:0006670Impaired myocardial contractilityExcluded (0%)
HP:0000597OphthalmoparesisVery rare (<1-4%)
HP:0002153HyperkalemiaVery rare (<1-4%)
HP:0002203Respiratory paralysisVery rare (<1-4%)

Identifiers

Disease identifiers

FieldValue
Canonical namethyrotoxic periodic paralysis
Mondo IDMONDO:0019201
OMIM188580
Orphanet79102
ICD-111457837313
SNOMED CT30967002
UMLSC0268446
MedGen120639
GARD0010814
MedDRA10043788
Is cancer (heuristic)no

Also known as: thyrotoxic hypokalemic periodic paralysis

Data availability: 80 GWAS associations (6 studies).

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn metal metabolism disorder › familial periodic paralysis › thyrotoxic periodic paralysis

Related subtypes (5): Andersen-Tawil syndrome, hypokalemic periodic paralysis, hyperkalemic periodic paralysis, normokalemic periodic paralysis, periodic paralysis with later-onset distal motor neuropathy

Genetics & variants

GWAS landscape

80 GWAS associations across 6 studies. Top hits map to 7 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs3127298e-29CALM2P1 - CASC17?2.08
rs3126916e-24CALM2P1 - CASC17C2.02
rs6230111e-22CALM2P1 - CASC17?1.96
rs3127432e-22CALM2P1 - CASC17T2.66
rs49472963e-22RNU6-1133P - C6orf15?2.06
rs22813882e-18HLA-DPA2?1.74
rs15214e-18MICA-AS1?2.51
rs64576172e-17HLA-DQB1 - MTCO3P1?1.74
rs124512952e-13CALM2P1 - CASC17C1.61
rs4110791e-10CALM2P1 - CASC17?1.64
rs1127233705e-10HCP5T2.63
rs68271972e-09FHDC1 - TRIM2T4.39
rs13527141e-08DCHS2T1.58
rs177148602e-08CALM2P1 - CASC17?1.74
rs64203873e-08ZFHX3T1.86
rs169757924e-08CALM2P1 - CASC17?1.46
rs59128386e-08CTHRC1P1 - KIF4CP?1.62
rs72225036e-08CALM2P1 - CASC17?1.79
rs1440974538e-08LRMDA - ATP5MC1P8T4.23
chr18:39153919e-08T0.23
chr20:60506221e-07A2.29
rs21865643e-07AAMDC?1.5
chr6:310039236e-07A1.74
chr6:306031837e-07A0.55
chr4:407001359e-07A1.81
rs169756941e-06CALM2P1 - CASC17?1.45
chr9:43674731e-06T0.37
chr18:558443001e-06C0.37
chr1:2011380341e-06C0.64
chr6:303510042e-06T0.55

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST011933Hoi-Yee Li G20203193,516Genome-wide meta-analysis reveals novel susceptibility loci for thyrotoxic periodic paralysis.
GCST011932Hoi-Yee Li G20203063,516Genome-wide meta-analysis reveals novel susceptibility loci for thyrotoxic periodic paralysis.
GCST008364Zhao SX20191710Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.
GCST008365Zhao SX20191712,160Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.
GCST001437Jongjaroenprasert W2012780A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis.
GCST001627Cheung CL2012691,170Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding2
Tier 2: splice/UTR0
Tier 3: regulatory2
Tier 4: intronic/intergenic46

MAF distribution

BucketVariants
common (>=0.05)37
low_freq (0.01-0.05)13
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
unknown27
intergenic_variant9
intron_variant8
non_coding_transcript_exon_variant2
regulatory_region_variant2
missense_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs3127291770310696G>A,T0.47intergenic_variantCALM2P1 - CASC178e-29Tier 4: intronic/intergenic
rs3126911770330197T>C0.46intron_variantCALM2P1 - CASC176e-24Tier 4: intronic/intergenic
rs6230111770263305A>C,G,T0.46intergenic_variantCALM2P1 - CASC171e-22Tier 4: intronic/intergenic
rs3127431770322496T>C0.497intron_variantCALM2P1 - CASC172e-22Tier 4: intronic/intergenic
rs4947296631090401T>A,C0.14intergenic_variantRNU6-1133P - C6orf153e-22Tier 4: intronic/intergenic
rs2281388633092341G>A,C,T0.33non_coding_transcript_exon_variantHLA-DPA22e-18Tier 4: intronic/intergenic
rs1521631382927C>G,T0.19non_coding_transcript_exon_variantMICA-AS14e-18Tier 4: intronic/intergenic
rs6457617632696074C>A,T0.47intergenic_variantHLA-DQB1 - MTCO3P12e-17Tier 4: intronic/intergenic
rs124512951770380682C>T0.49intergenic_variantCALM2P1 - CASC172e-13Tier 4: intronic/intergenic
rs4110791770295230C>A,T0.33intron_variantCALM2P1 - CASC171e-10Tier 4: intronic/intergenic
rs112723370631466032T>G0.208intron_variantHCP55e-10Tier 4: intronic/intergenic
rs68271974153115388C>T0.026regulatory_region_variantFHDC1 - TRIM22e-09Tier 3: regulatory
rs13527144154322452T>A,C,G0.14missense_variantDCHS21e-08Tier 1: coding
rs177148601770276213G>A0.21intergenic_variantCALM2P1 - CASC172e-08Tier 4: intronic/intergenic
rs64203871673269314T>C,G0.158intron_variantZFHX33e-08Tier 4: intronic/intergenic
rs169757921770437584A>G,T0.43intron_variantCALM2P1 - CASC174e-08Tier 4: intronic/intergenic
rs5912838X79241621A>C,G0.42intergenic_variantCTHRC1P1 - KIF4CP6e-08Tier 4: intronic/intergenic
rs72225031770303644G>T0.18intron_variantCALM2P1 - CASC176e-08Tier 4: intronic/intergenic
rs1440974531076600331C>T0.019intergenic_variantLRMDA - ATP5MC1P88e-08Tier 4: intronic/intergenic
chr18:39153910.029e-08Tier 4: intronic/intergenic
chr20:60506220.0731e-07Tier 4: intronic/intergenic
rs21865641177872220G>A0.17missense_variantAAMDC3e-07Tier 1: coding
chr6:310039230.1586e-07Tier 4: intronic/intergenic
chr6:306031830.1267e-07Tier 4: intronic/intergenic
chr4:407001350.3439e-07Tier 4: intronic/intergenic
rs169756941770384516T>A,C0.31intergenic_variantCALM2P1 - CASC171e-06Tier 4: intronic/intergenic
chr9:43674730.0291e-06Tier 4: intronic/intergenic
chr18:558443000.0341e-06Tier 4: intronic/intergenic
chr1:2011380340.4991e-06Tier 4: intronic/intergenic
chr6:303510040.122e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 22 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SOX9Orphanet:140Campomelic dysplasia
SOX9Orphanet:213846,XX ovotesticular difference of sex development
SOX9Orphanet:24246,XY complete gonadal dysgenesis
SOX9Orphanet:25151046,XY partial gonadal dysgenesis
SOX9Orphanet:39346,XX testicular difference of sex development
SOX9Orphanet:718Isolated Pierre Robin sequence
TRIM2Orphanet:397968Charcot-Marie-Tooth disease type 2R
COL11A2Orphanet:1427Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2Orphanet:166100Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2Orphanet:2021Fibrochondrogenesis
COL11A2Orphanet:90635Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2Orphanet:90636Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
HLA-DPB1Orphanet:133Chronic beryllium disease
HLA-DPB1Orphanet:900Granulomatosis with polyangiitis
HLA-DQB1Orphanet:2073Narcolepsy type 1
HLA-DQB1Orphanet:477738Pediatric multiple sclerosis
HLA-DQB1Orphanet:703Bullous pemphigoid
HLA-DQB1Orphanet:83465Narcolepsy type 2
HLA-DQB1Orphanet:930Idiopathic achalasia
KCNJ2Orphanet:334Hereditary atrial fibrillation
KCNJ2Orphanet:37553Andersen-Tawil syndrome
KCNJ2Orphanet:51083Congenital short QT syndrome

Cohort genes → proteins

13 cohort genes, 12 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only13

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SOX9HGNC:11204ENSG00000125398P48436Transcription factor SOX-9gwas
C6orf15HGNC:13927ENSG00000204542Q6UXA7Uncharacterized protein C6orf15gwas
TRIM2HGNC:15974ENSG00000109654Q9C040Tripartite motif-containing protein 2gwas
COL11A2HGNC:2187ENSG00000204248P13942Collagen alpha-2(XI) chaingwas
DCHS2HGNC:23111ENSG00000197410Q6V1P9Protocadherin-23gwas
CYCSP5HGNC:24416ENSG00000227735CYCS pseudogene 5gwas
AAMDCHGNC:30205ENSG00000087884Q9H7C9Mth938 domain-containing proteingwas
HLA-DPB1HGNC:4940ENSG00000223865P04440HLA class II histocompatibility antigen, DP beta 1 chaingwas
HLA-DQA2HGNC:4943ENSG00000237541P01906HLA class II histocompatibility antigen, DQ alpha 2 chaingwas
HLA-DQB1HGNC:4944ENSG00000179344P01920HLA class II histocompatibility antigen, DQ beta 1 chaingwas
ITM2AHGNC:6173ENSG00000078596O43736Integral membrane protein 2Agwas
KCNJ16HGNC:6262ENSG00000153822Q9NPI9Inward rectifier potassium channel 16gwas
KCNJ2HGNC:6263ENSG00000123700P63252Inward rectifier potassium channel 2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SOX9Transcription factor SOX-9Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
TRIM2Tripartite motif-containing protein 2UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11.
COL11A2Collagen alpha-2(XI) chainMay play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
DCHS2Protocadherin-23Calcium-dependent cell-adhesion protein.
AAMDCMth938 domain-containing proteinMay play a role in preadipocyte differentiation and adipogenesis.
HLA-DPB1HLA class II histocompatibility antigen, DP beta 1 chainBinds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQA2HLA class II histocompatibility antigen, DQ alpha 2 chainBinds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB1HLA class II histocompatibility antigen, DQ beta 1 chainBinds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
KCNJ16Inward rectifier potassium channel 16Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.
KCNJ2Inward rectifier potassium channel 2Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

Protein-family classification

Druggable: 5 · Difficult: 2 · Unknown: 6 · Druggable fraction: 0.38

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.

FamilyGenesFoldFDR
Ion channel217.2×0.018
Antibody/Immunoglobulin36.7×0.018
Transcription factor21.3×0.639
Other/Unknown60.8×0.837

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SOX9Transcription factornoHMG_box_dom, Sox_N, HMG_box_dom_sf
C6orf15Other/UnknownnoC6orf15
TRIM2Transcription factornoZnf_B-box, NHL_repeat, Filamin/ABP280_rpt
COL11A2Other/UnknownnoFib_collagen_C, Laminin_G, Collagen
DCHS2Other/UnknownnoCadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CYCSP5Other/Unknownno
AAMDCOther/UnknownnoNDUFAF3/AAMDC, AAMDC, MTH938-like_sf
HLA-DPB1Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQA2Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
ITM2AOther/UnknownnoBRICHOS_dom, ITM2
KCNJ16Ion channelyesK_chnl_inward-rec_Kir5, K_chnl_inward-rec_Kir_cyto, Ig_E-set
KCNJ2Ion channelyesK_chnl_inward-rec_Kir2.1, K_chnl_inward-rec_Kir_cyto, K_chnl_inward-rec_Kir_N

Expression context

Cohort genes with no expression data: 0.

10 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)13
unknown0

Top tissues across cohort

TissueCohort genes
male germ line stem cell (sensu Vertebrata) in testis3
corpus callosum2
dorsal motor nucleus of vagus nerve2
granulocyte2
vermiform appendix2
cranial nerve II1
hair follicle1
ventricular zone1
skin of abdomen1
skin of leg1
zone of skin1
inferior olivary complex1
adenohypophysis1
pituitary gland1
calcaneal tendon1
prefrontal cortex1
superior frontal gyrus1
primordial germ cell in gonad1
apex of heart1
hindlimb stylopod muscle1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SOX9274ubiquitousmarkerventricular zone, cranial nerve II, hair follicle
C6orf1531tissue_specificyesskin of leg, zone of skin, skin of abdomen
TRIM2284ubiquitousmarkerinferior olivary complex, dorsal motor nucleus of vagus nerve, corpus callosum
COL11A2134broadyespituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis
DCHS2120tissue_specificmarkerprefrontal cortex, calcaneal tendon, superior frontal gyrus
CYCSP597yesprimordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, corpus callosum
AAMDC287ubiquitousmarkertendon of biceps brachii, hindlimb stylopod muscle, apex of heart
HLA-DPB1135ubiquitousmarkergranulocyte, lymph node, vermiform appendix
HLA-DQA2127broadmarkergranulocyte, vermiform appendix, male germ line stem cell (sensu Vertebrata) in testis
HLA-DQB1268broadmarkerright lung, spleen, upper lobe of left lung
ITM2A289broadmarkerthymus, cartilage tissue, vena cava
KCNJ16212broadmarkerrenal medulla, nephron tubule, caput epididymis
KCNJ2256ubiquitousmarkerinferior vagus X ganglion, skeletal muscle tissue of rectus abdominis, dorsal motor nucleus of vagus nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SOX94,935
HLA-DQA21,611
COL11A21,583
ITM2A1,423
C6orf151,420
TRIM21,275
KCNJ16894
DCHS2882
AAMDC831
HLA-DPB1160

Structural data

PDB: 7 · AlphaFold-only: 5 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
HLA-DPB1P0444010
HLA-DQB1P0192010
TRIM2Q9C0406
KCNJ16Q9NPI94
KCNJ2P632523
AAMDCQ9H7C92
SOX9P484361

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
HLA-DQA2P0190689.29
ITM2AO4373680.66
COL11A2P1394250.18
C6orf15Q6UXA743.65
DCHS2Q6V1P9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 13 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Interferon gamma signaling462.8×1e-05TRIM2, HLA-DPB1, HLA-DQA2, HLA-DQB1
G protein gated Potassium channels2285.5×5e-04KCNJ16, KCNJ2
Inwardly rectifying K+ channels2178.4×6e-04KCNJ16, KCNJ2
Translocation of ZAP-70 to Immunological synapse2158.6×6e-04HLA-DPB1, HLA-DQA2
Activation of GABAB receptors2150.3×6e-04KCNJ16, KCNJ2
Phosphorylation of CD3 and TCR zeta chains2135.9×6e-04HLA-DPB1, HLA-DQA2
GABA B receptor activation2135.9×6e-04KCNJ16, KCNJ2
Co-inhibition by PD-12129.8×6e-04HLA-DPB1, HLA-DQA2
Activation of G protein gated Potassium channels298.5×8e-04KCNJ16, KCNJ2
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits298.5×8e-04KCNJ16, KCNJ2
Generation of second messenger molecules286.5×1e-03HLA-DPB1, HLA-DQA2
GABA receptor activation279.3×0.001KCNJ16, KCNJ2
Developmental Lineage of Pancreatic Ductal Cells257.1×0.002SOX9, COL11A2
Sensory perception of sour taste1713.8×0.005KCNJ2
Potassium Channels233.6×0.005KCNJ16, KCNJ2
Downstream TCR signaling232.1×0.005HLA-DPB1, HLA-DQA2
Potassium transport channels1475.8×0.006KCNJ16
Classical Kir channels1356.9×0.007KCNJ2
Neurotransmitter receptors and postsynaptic signal transmission225.0×0.007KCNJ16, KCNJ2
MHC class II antigen presentation222.3×0.008HLA-DPB1, HLA-DQA2
Transmission across Chemical Synapses219.0×0.010KCNJ16, KCNJ2
Transcriptional regulation of testis differentiation189.2×0.024SOX9
Phase 4 - resting membrane potential175.1×0.025KCNJ2
Developmental Lineage of Multipotent Pancreatic Progenitor Cells175.1×0.025SOX9
Neuronal System211.1×0.025KCNJ16, KCNJ2
MET activates PTK2 signaling147.6×0.038COL11A2
Sensory perception of taste142.0×0.042KCNJ2
Developmental Lineage of Pancreatic Acinar Cells137.6×0.045SOX9
Collagen chain trimerization132.4×0.050COL11A2
Transcriptional regulation by RUNX2131.7×0.050SOX9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
peptide antigen assembly with MHC class II protein complex3263.3×3e-05HLA-DPB1, HLA-DQA2, HLA-DQB1
antigen processing and presentation of exogenous peptide antigen via MHC class II3135.9×1e-04HLA-DPB1, HLA-DQA2, HLA-DQB1
positive regulation of immune response3120.4×1e-04HLA-DPB1, HLA-DQA2, HLA-DQB1
positive regulation of T cell activation3110.9×1e-04HLA-DPB1, HLA-DQA2, HLA-DQB1
regulation of monoatomic ion transmembrane transport2122.1×0.004KCNJ16, KCNJ2
adaptive immune response321.1×0.010HLA-DPB1, HLA-DQA2, HLA-DQB1
potassium ion import across plasma membrane261.1×0.012KCNJ16, KCNJ2
regulation of skeletal muscle contraction via regulation of action potential11404.3×0.014KCNJ2
negative regulation of immune system process1702.2×0.014SOX9
epithelial cell proliferation involved in prostatic bud elongation1702.2×0.014SOX9
regulation of cell proliferation involved in tissue homeostasis1702.2×0.014SOX9
regulation of branching involved in lung morphogenesis1702.2×0.014SOX9
cell proliferation involved in heart morphogenesis1702.2×0.014SOX9
regulation of epithelial cell proliferation involved in lung morphogenesis1702.2×0.014SOX9
heart valve formation1468.1×0.014SOX9
neural crest cell fate specification1468.1×0.014SOX9
male germ-line sex determination1468.1×0.014SOX9
intrahepatic bile duct development1468.1×0.014SOX9
bronchus cartilage development1468.1×0.014SOX9
lung smooth muscle development1468.1×0.014SOX9
condensed mesenchymal cell proliferation1468.1×0.014DCHS2
ureter urothelium development1468.1×0.014SOX9
ureter smooth muscle cell differentiation1468.1×0.014SOX9
relaxation of skeletal muscle1468.1×0.014KCNJ2
negative regulation of beta-catenin-TCF complex assembly1468.1×0.014SOX9
cartilage development241.9×0.014SOX9, COL11A2
cellular response to mechanical stimulus236.0×0.014SOX9, KCNJ2
potassium ion transport231.9×0.014KCNJ16, KCNJ2
glial cell fate specification1351.1×0.015SOX9
tissue morphogenesis1351.1×0.015DCHS2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 13

Druggability breadth: 3 of 13 evidence-associated genes (23%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
SOX900
C6orf1500
TRIM200
COL11A200
DCHS200
CYCSP500
AAMDC00
HLA-DPB100
HLA-DQA200
HLA-DQB100

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
KCNJ231Binding:23, ADMET:8
SOX93Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug4HLA-DPB1, HLA-DQB1, KCNJ16, KCNJ2
DDruggable family + AlphaFold only, no drug1HLA-DQA2
EDifficult family or no structure, no drug8SOX9, C6orf15, TRIM2, COL11A2, DCHS2, CYCSP5, AAMDC, ITM2A

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SOX93—
C6orf150—
TRIM20—
COL11A20—
DCHS20—
CYCSP50—
AAMDC0—
HLA-DPB10—
HLA-DQA20—
HLA-DQB10—
ITM2A0—
KCNJ160—
KCNJ231—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified2

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00443833Not specifiedCOMPLETEDGenetic Analysis of Thyrotoxic Periodic Paralysis
NCT02287363Not specifiedUNKNOWNGenetic and Morphological Analysis of Thyrotoxic Periodic Paralysis

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 70

This page pulls from 70 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd11intactinterpromeddramedgenmeshmimmondomondochildmondoparentorphanetpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot