Incontinentia pigmenti

Summary

Incontinentia pigmenti (MONDO:0010631) is a disease caused by IKBKG (GenCC Definitive), with 4 cohort genes and 2 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: IKBKG (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 30
• Phenotypes (HPO): 67
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.2	Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.62	United States	Validated
Point prevalence	1-9 / 1 000 000		Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

67 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000668	Hypodontia	Very frequent (80-99%)
HP:0000988	Skin rash	Very frequent (80-99%)
HP:0001000	Abnormality of skin pigmentation	Very frequent (80-99%)
HP:0001053	Hypopigmented skin patches	Very frequent (80-99%)
HP:0001231	Abnormal fingernail morphology	Very frequent (80-99%)
HP:0001595	Abnormality of the hair	Very frequent (80-99%)
HP:0001597	Abnormality of the nail	Very frequent (80-99%)
HP:0001804	Hypoplastic fingernail	Very frequent (80-99%)
HP:0007400	Irregular hyperpigmentation	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0010783	Erythema	Very frequent (80-99%)
HP:0100585	Telangiectasia of the skin	Very frequent (80-99%)
HP:0200043	Verrucae	Very frequent (80-99%)
HP:0000202	Orofacial cleft	Frequent (30-79%)
HP:0000364	Hearing abnormality	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000684	Delayed eruption of teeth	Frequent (30-79%)
HP:0000962	Hyperkeratosis	Frequent (30-79%)
HP:0000975	Hyperhidrosis	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0001880	Eosinophilia	Frequent (30-79%)
HP:0002558	Supernumerary nipple	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002797	Osteolysis	Frequent (30-79%)
HP:0004097	Deviation of finger	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0005815	Supernumerary ribs	Frequent (30-79%)
HP:0005922	Abnormal hand morphology	Frequent (30-79%)
HP:0006482	Abnormal dental morphology	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0007957	Corneal opacity	Frequent (30-79%)
HP:0010978	Abnormality of immune system physiology	Frequent (30-79%)
HP:0100490	Camptodactyly of finger	Frequent (30-79%)
HP:0100555	Asymmetric growth	Frequent (30-79%)
HP:0200042	Skin ulcer	Frequent (30-79%)
HP:0000491	Keratitis	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000532	Chorioretinal abnormality	Occasional (5-29%)
HP:0000541	Retinal detachment	Occasional (5-29%)
HP:0000554	Uveitis	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0000573	Retinal hemorrhage	Occasional (5-29%)
HP:0000592	Blue sclerae	Occasional (5-29%)
HP:0000682	Abnormality of dental enamel	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	incontinentia pigmenti
Mondo ID	MONDO:0010631
MeSH	D007184
OMIM	308300
Orphanet	464
DOID	DOID:12305
ICD-10-CM	Q82.3
ICD-11	1542530268
NCIT	C84787
SNOMED CT	367520004
UMLS	C0021171
MedGen	7049
GARD	0006778
NORD	1300
Is cancer (heuristic)	no

Also known as: Bloch-Siemens syndrome · Bloch-Sulzberger syndrome · incontinentia pigmenti · Incontinentia pigmenti syndrome · Incontinentia pigmenti type 2 (formerly) · incontinentia pigmenti, X-linked dominant · IP · IP2 (formerly)

Data availability: 30 ClinVar variants · 6 GenCC gene-disease records · 10 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › incontinentia pigmenti

Related subtypes (119): ADULT syndrome, autosomal dominant palmoplantar keratoderma and congenital alopecia, ameloonychohypohidrotic syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, anonychia with flexural pigmentation, Böök syndrome, blepharocheilodontic syndrome, Stern-Lubinsky-Durrie syndrome, dermatopathia pigmentosa reticularis, dermo-odonto dysplasia, Rapp-Hodgkin syndrome, Clouston syndrome, ectodermal dysplasia, trichoodontoonychial type, gingival fibromatosis-hypertrichosis syndrome, hypertrichosis cubiti-short stature syndrome, Johnson neuroectodermal syndrome, Marshall syndrome, Naegeli-Franceschetti-Jadassohn syndrome, oculodentodigital dysplasia, Cronkhite-Canada syndrome, scalp-ear-nipple syndrome, tooth and nail syndrome, tricho-dento-osseous syndrome, tricho-retino-dento-digital syndrome, acrofacial dysostosis, Weyers type, Ackerman syndrome, alopecia - contractures - dwarfism - intellectual disability syndrome, AREDYLD syndrome, Barber-Say syndrome, oculoosteocutaneous syndrome, cataract-hypertrichosis-intellectual disability syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, cerebellar ataxia-ectodermal dysplasia syndrome, cranioectodermal dysplasia, conductive deafness-ptosis-skeletal anomalies syndrome, dermatoosteolysis, Kirghizian type, Dubowitz syndrome, ectodermal dysplasia-sensorineural deafness syndrome, ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome, hypohidrotic ectodermal dysplasia-hypothyroidism-ciliary dyskinesia syndrome, cleft lip/palate-ectodermal dysplasia syndrome, EEM syndrome, Ellis-van Creveld syndrome, amelocerebrohypohidrotic syndrome, GAPO syndrome, ichthyosis-alopecia-eclabion-ectropion-intellectual disability syndrome, Leukomelanoderma-infantilism-intellectual disability-hypodontia-hypotrichosis syndrome, Dahlberg-Borer-Newcomer syndrome, cartilage-hair hypoplasia, oculotrichodysplasia, pilodental dysplasia-refractive errors syndrome, Bartsocas-Papas syndrome 1, ectodermal dysplasia-blindness syndrome, Schinzel-Giedion syndrome, Teebi-Shaltout syndrome, taurodontia-absent teeth-sparse hair syndrome, odontotrichomelic syndrome, trichomegaly-retina pigmentary degeneration-dwarfism syndrome, trichoodontoonychial dysplasia, CHIME syndrome, anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome, Ito hypomelanosis, contractures-ectodermal dysplasia-cleft lip/palate syndrome, Toriello-Lacassie-Droste syndrome, odontomicronychial dysplasia, ectodermal dysplasia with natal teeth, Turnpenny type, hidrotic ectodermal dysplasia, Christianson-Fourie type, trichodental syndrome, congenital hypotrichosis with juvenile macular dystrophy, tricho-oculo-dermo-vertebral syndrome, odonto-tricho-ungual-digito-palmar syndrome, Fried’s tooth and nail syndrome, limb-mammary syndrome, epidermolysis bullosa simplex due to plakophilin deficiency, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, Curly hair - acral keratoderma - caries syndrome, hypotrichosis-osteolysis-periodontitis-palmoplantar keratoderma syndrome, Lelis syndrome, Fontaine progeroid syndrome, ectodermal dysplasia-syndactyly syndrome, ectodermal dysplasia 5, hair/nail type, nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome, ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type, cardiofaciocutaneous syndrome, choroidal atrophy-alopecia syndrome, dyskeratosis congenita, hidrotic ectodermal dysplasia, Halal type, hypertrichosis lanuginosa congenita, hypohidrotic ectodermal dysplasia, odonto-onycho dysplasia-alopecia syndrome, pili torti-onychodysplasia syndrome, chondroectodermal dysplasia with night blindness, trichorhinophalangeal syndrome, trichothiodystrophy, trichodermodysplasia-dental alterations syndrome, autosomal dominant trichoodontoonychodysplasia-syndactyly, focal facial dermal dysplasia, KID syndrome, pure hair and nail ectodermal dysplasia, circumscribed palmoplantar hypokeratosis, trichodysplasia-amelogenesis imperfecta syndrome, dermotrichic syndrome, alves Castelo dos Santos syndrome, Brunoni syndrome, ectodermal dysplasia Bartalos type, ectodermal dysplasia margarita type, ectodermal dysplasia alopecia preaxial polydactyly, ectodermal dysplasia arthrogryposis diabetes mellitus, ectodermal dysplasia blindness, ectodermal dysplasia neurosensory deafness, ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, ectodermal dysplasia 15, hypohidrotic/hair type, linear hypopigmentation and craniofacial asymmetry with acral, ocular and brain anomalies, jones hersh yusk syndrome, ectodermal dysplasia 13, hair/tooth type, arthrogryposis-ectodermal dysplasia-other anomalies syndrome, ectodermal dysplasia WNT10A related, CTSC-related disorder, ectodermal dysplasia 17 with or without limb malformations

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

30 retrieved; paginated sample, class counts are floors:

18 pathogenic, 4 likely pathogenic, 3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 likely benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1684654	Single allele	ATP6AP1	Pathogenic	criteria provided, single submitter
1325735	NC_000023.10:g.(153784642_153786697)_(153792726_153814360)del	CTAG1A	Pathogenic	criteria provided, single submitter
11447	NC_000023.11:g.(154556377_154558531)(154565046?)del	IKBKG	Pathogenic	no assertion criteria provided
11448	NM_001099857.5(IKBKG):c.1110dup (p.Ala371fs)	IKBKG	Pathogenic	criteria provided, single submitter
11450	NM_001099857.5(IKBKG):c.1259A>G (p.Ter420Trp)	IKBKG	Pathogenic	no assertion criteria provided
11451	NM_001099857.5(IKBKG):c.120_129dup (p.Glu44fs)	IKBKG	Pathogenic	no assertion criteria provided
11452	NM_001099857.5(IKBKG):c.184C>T (p.Arg62Ter)	IKBKG	Pathogenic	criteria provided, single submitter
11458	NM_001099857.5(IKBKG):c.1166_1178dup (p.Asp394fs)	IKBKG	Pathogenic	no assertion criteria provided
3242266	NM_001099857.5(IKBKG):c.373del (p.Val125fs)	IKBKG	Pathogenic	criteria provided, single submitter
372387	NM_001099857.5(IKBKG):c.1167dup (p.Glu390fs)	IKBKG	Pathogenic	criteria provided, multiple submitters, no conflicts
4683109	NC_000023.11:g.154558015_154569698del	IKBKG	Pathogenic	criteria provided, single submitter
4848452	NM_001099857.5(IKBKG):c.805C>T (p.Gln269Ter)	IKBKG	Pathogenic	criteria provided, single submitter
4848493	NM_001099857.5(IKBKG):c.1110del (p.Ala371fs)	IKBKG	Pathogenic	criteria provided, single submitter
503711	NM_001099857.5(IKBKG):c.519-3_519dup	IKBKG	Pathogenic	criteria provided, multiple submitters, no conflicts
619016	NM_001099857.5(IKBKG):c.518+866C>T	IKBKG	Pathogenic	criteria provided, single submitter
916678	IKBKG, 2-BP DEL, 1182TT	IKBKG	Pathogenic	no assertion criteria provided
916682	NM_001099857.5(IKBKG):c.1117+1G>A	IKBKG	Pathogenic	no assertion criteria provided
932047	NM_001099857.5(IKBKG):c.358C>T (p.Gln120Ter)	IKBKG	Pathogenic	criteria provided, single submitter
974981	NM_001099857.5(IKBKG):c.706C>T (p.Gln236Ter)	IKBKG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11457	NM_001099857.5(IKBKG):c.1217A>T (p.Asp406Val)	IKBKG	Likely pathogenic	criteria provided, single submitter
2579743	NM_001099857.5(IKBKG):c.363_367del (p.Leu122fs)	IKBKG	Likely pathogenic	criteria provided, single submitter
4293339	NM_001099857.5(IKBKG):c.574C>T (p.Gln192Ter)	IKBKG	Likely pathogenic	criteria provided, single submitter
449462	NM_001099857.5(IKBKG):c.1117+5G>C	IKBKG	Likely pathogenic	criteria provided, single submitter
11449	NM_001099857.5(IKBKG):c.1219A>G (p.Met407Val)	IKBKG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3602637	NM_001099857.5(IKBKG):c.523C>T (p.Arg175Trp)	IKBKG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3376313	NM_001099856.6(IKBKG):c.104G>C (p.Ser35Thr)	G6PD	Uncertain significance	criteria provided, single submitter
625962	NM_001321396.3(IKBKG):c.-16+3G>A	G6PD	Uncertain significance	criteria provided, single submitter
1527844	NM_001099857.5(IKBKG):c.760C>G (p.Arg254Gly)	IKBKG	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891377	NM_001099857.5(IKBKG):c.151C>T (p.Leu51Phe)	IKBKG	Likely benign	criteria provided, single submitter
68234	NM_001099857.5(IKBKG):c.169G>A (p.Glu57Lys)	IKBKG	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 6 · 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
IKBKG	Definitive	X-linked	incontinentia pigmenti	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IKBKG	Orphanet:464	Incontinentia pigmenti
IKBKG	Orphanet:69088	Hypohidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome
IKBKG	Orphanet:699605	NEMO deleted exon 5 autoinflammatory syndrome
IKBKG	Orphanet:98813	Hypohidrotic ectodermal dysplasia with immunodeficiency
G6PD	Orphanet:466026	Class I glucose-6-phosphate dehydrogenase deficiency
ATP6AP1	Orphanet:692790	ATP6AP1-CDG

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
IKBKG	HGNC:5961	ENSG00000269335	Q9Y6K9	NF-kappa-B essential modulator	gencc,clinvar
CTAG1A	HGNC:24198	ENSG00000268651	P78358	Cancer/testis antigen 1	clinvar
G6PD	HGNC:4057	ENSG00000160211	P11413	Glucose-6-phosphate 1-dehydrogenase	clinvar
ATP6AP1	HGNC:868	ENSG00000071553	Q15904	V-type proton ATPase subunit S1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IKBKG	NF-kappa-B essential modulator	Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor.
G6PD	Glucose-6-phosphate 1-dehydrogenase	Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.
ATP6AP1	V-type proton ATPase subunit S1	Accessory subunit of the proton-transporting vacuolar (V)-ATPase protein pump, which is required for luminal acidification of secretory vesicles.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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)	1	3.0×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IKBKG	Other/Unknown	no		NEMO_N, CC2-LZ_dom, NEMO_ZF
CTAG1A	Other/Unknown	no		CTAG/Pcc1
G6PD	Enzyme (other)	yes	1.1.1.49	G6P_DH, G6P_DH_AS, G6P_DH_NAD-bd
ATP6AP1	Other/Unknown	no		Ac45_acc_su, VAS1_LD, VAS1/VOA1_TM

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
granulocyte	2
right testis	2
blood	1
spleen	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
stromal cell of endometrium	1
Brodmann (1909) area 10	1
endometrium epithelium	1
paraflocculus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IKBKG	134	ubiquitous	marker	granulocyte, blood, spleen
CTAG1A	26	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
G6PD	218	ubiquitous	marker	stromal cell of endometrium, granulocyte, right testis
ATP6AP1	291	ubiquitous	marker	endometrium epithelium, Brodmann (1909) area 10, paraflocculus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IKBKG	4,981
G6PD	4,226
ATP6AP1	1,759
CTAG1A	1,470

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
G6PD	P11413	25
CTAG1A	P78358	23
IKBKG	Q9Y6K9	17
ATP6AP1	Q15904	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 95. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

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

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
IKBKB deficiency causes SCID	1	1268.9×	0.025	IKBKG
IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)	1	1268.9×	0.025	IKBKG
SLC15A4:TASL-dependent IRF5 activation	1	634.4×	0.025	IKBKG
IkBA variant leads to EDA-ID	1	543.8×	0.025	IKBKG
NFE2L2 regulates pentose phosphate pathway genes	1	475.8×	0.025	G6PD
ZBP1(DAI) mediated induction of type I IFNs	1	346.1×	0.025	IKBKG
SUMOylation of immune response proteins	1	317.2×	0.025	IKBKG
Pentose phosphate pathway	1	317.2×	0.025	G6PD
Diseases of Immune System	1	292.8×	0.025	IKBKG
Diseases associated with the TLR signaling cascade	1	292.8×	0.025	IKBKG
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	292.8×	0.025	IKBKG
Downstream signaling events of B Cell Receptor (BCR)	1	271.9×	0.025	IKBKG
IRAK1 recruits IKK complex	1	271.9×	0.025	IKBKG
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation	1	271.9×	0.025	IKBKG
MAP3K8 (TPL2)-dependent MAPK1/3 activation	1	237.9×	0.025	IKBKG
RIP-mediated NFkB activation via ZBP1	1	223.9×	0.025	IKBKG
Regulation of NF-kappa B signaling	1	211.5×	0.025	IKBKG
TICAM1, RIP1-mediated IKK complex recruitment	1	200.3×	0.025	IKBKG
Modulation of host responses by IFN-stimulated genes	1	200.3×	0.025	IKBKG
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	1	173.0×	0.025	IKBKG
TCR signaling	1	165.5×	0.025	IKBKG
activated TAK1 mediates p38 MAPK activation	1	165.5×	0.025	IKBKG
IKK complex recruitment mediated by RIP1	1	165.5×	0.025	IKBKG
TRAF6 mediated NF-kB activation	1	152.3×	0.026	IKBKG
TNF signaling	1	141.0×	0.026	IKBKG
Insulin receptor recycling	1	126.9×	0.026	ATP6AP1
Transferrin endocytosis and recycling	1	122.8×	0.026	ATP6AP1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	119.0×	0.026	IKBKG
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	119.0×	0.026	IKBKG
Signaling by the B Cell Receptor (BCR)	1	115.3×	0.026	IKBKG

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
ribose phosphate biosynthetic process	1	4213.0×	0.007	G6PD
response to iron(III) ion	1	2106.5×	0.007	G6PD
pentose biosynthetic process	1	2106.5×	0.007	G6PD
positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1	2106.5×	0.007	G6PD
pentose-phosphate shunt, oxidative branch	1	1053.2×	0.009	G6PD
obsolete regulation of cellular pH	1	842.6×	0.009	ATP6AP1
endosome to plasma membrane protein transport	1	842.6×	0.009	ATP6AP1
tRNA threonylcarbamoyladenosine metabolic process	1	702.2×	0.009	CTAG1A
establishment of vesicle localization	1	601.9×	0.009	IKBKG
osteoclast development	1	526.6×	0.009	ATP6AP1
cellular response to increased oxygen levels	1	526.6×	0.009	ATP6AP1
Golgi lumen acidification	1	421.3×	0.010	ATP6AP1
pentose-phosphate shunt	1	383.0×	0.010	G6PD
NADP+ metabolic process	1	383.0×	0.010	G6PD
negative regulation of cell growth involved in cardiac muscle cell development	1	351.1×	0.010	G6PD
anoikis	1	324.1×	0.010	IKBKG
glucose 6-phosphate metabolic process	1	324.1×	0.010	G6PD
endosomal lumen acidification	1	300.9×	0.010	ATP6AP1
intracellular pH reduction	1	300.9×	0.010	ATP6AP1
synaptic vesicle lumen acidification	1	234.1×	0.011	ATP6AP1
negative regulation of reactive oxygen species metabolic process	1	234.1×	0.011	G6PD
erythrocyte maturation	1	210.7×	0.011	G6PD
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	210.7×	0.011	IKBKG
positive regulation of T cell receptor signaling pathway	1	191.5×	0.012	IKBKG
vacuolar acidification	1	183.2×	0.012	ATP6AP1
regulation of neuron apoptotic process	1	175.5×	0.012	G6PD
lysosomal lumen acidification	1	168.5×	0.012	ATP6AP1
B cell homeostasis	1	140.4×	0.013	IKBKG
positive regulation of ubiquitin-dependent protein catabolic process	1	140.4×	0.013	IKBKG
positive regulation of macroautophagy	1	131.7×	0.014	IKBKG

Therapeutics

Drug target analysis

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

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
G6PD	BREXANOLONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
G6PD	8	4
IKBKG	0	0
CTAG1A	0	0
ATP6AP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
G6PD	49	Binding:46, ADMET:2, Functional:1
IKBKG	38	Binding:30, Functional:8
ATP6AP1	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
G6PD	1.1.1.49	glucose-6-phosphate dehydrogenase (NADP+)

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
G6PD	1

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)
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	G6PD
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	3	IKBKG, CTAG1A, ATP6AP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IKBKG	38	—
CTAG1A	0	—
ATP6AP1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT00976586	Not specified	COMPLETED	Role of Pseudogene in Incontinentia Pigmenti, and Its Potential Treatment