Piebaldism

Summary

Piebaldism (MONDO:0008244) is a disease caused by variants in KIT and SNAI2, with 4 cohort genes and 5 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal genes: KIT (GenCC Definitive), SNAI2 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 195
• Phenotypes (HPO): 19
• Clinical trials: 5

Clinical features

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0002211	White forelock	Very frequent (80-99%)
HP:0005599	Hypopigmentation of hair	Very frequent (80-99%)
HP:0007544	Piebaldism	Very frequent (80-99%)
HP:0001053	Hypopigmented skin patches	Frequent (30-79%)
HP:0002226	White eyebrow	Frequent (30-79%)
HP:0002227	White eyelashes	Frequent (30-79%)
HP:0012733	Macule	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000431	Wide nasal bridge	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)
HP:0001100	Heterochromia iridis	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0002251	Aganglionic megacolon	Occasional (5-29%)
HP:0002683	Abnormality of the calvaria	Occasional (5-29%)
HP:0008069	Neoplasm of the skin	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	piebaldism
Mondo ID	MONDO:0008244
MeSH	D016116
OMIM	172800
Orphanet	2884
DOID	DOID:3263
ICD-11	2089421143
NCIT	C85009
SNOMED CT	6479008
UMLS	C0080024
MedGen	36361
GARD	0004344
Is cancer (heuristic)	no

Also known as: PBT · piebald trait · piebaldism

Data availability: 195 ClinVar variants · 9 GenCC gene-disease records.

Disease family

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

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, 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, autosomal dominant hypocalcemia, 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

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

195 retrieved; paginated sample, class counts are floors:

89 uncertain significance, 54 conflicting classifications of pathogenicity, 23 benign/likely benign, 15 pathogenic, 5 likely benign, 4 likely pathogenic, 4 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703552	GRCh37/hg19 4q12(chr4:53688710-56491447)	CLOCK	Pathogenic	no assertion criteria provided
1299653	NM_000222.3(KIT):c.2415_2422del (p.Thr806fs)	KIT	Pathogenic	criteria provided, single submitter
13843	NM_000222.3(KIT):c.1990G>A (p.Gly664Arg)	KIT	Pathogenic	no assertion criteria provided
13844	NC_000004.12:g.(?54229292)(54740716_)del	KIT	Pathogenic	no assertion criteria provided
13847	NM_000222.3(KIT):c.1925_1926del (p.Lys642fs)	KIT	Pathogenic	no assertion criteria provided
13848	NM_000222.3(KIT):c.1681dup (p.Glu561fs)	KIT	Pathogenic	no assertion criteria provided
13850	NM_000222.3(KIT):c.253del (p.Glu85fs)	KIT	Pathogenic	no assertion criteria provided
13851	NM_000222.3(KIT):c.1879+1G>A	KIT	Pathogenic	criteria provided, single submitter
13861	NM_000222.3(KIT):c.2539A>C (p.Thr847Pro)	KIT	Pathogenic	no assertion criteria provided
13864	NM_000222.3(KIT):c.1751T>G (p.Phe584Cys)	KIT	Pathogenic	no assertion criteria provided
2442396	NM_000222.3(KIT):c.237del (p.Asn80fs)	KIT	Pathogenic	criteria provided, single submitter
3066083	NM_000222.3(KIT):c.2700T>A (p.Tyr900Ter)	KIT	Pathogenic	criteria provided, single submitter
4292892	NM_000222.3(KIT):c.1880-1G>A	KIT	Pathogenic	criteria provided, single submitter
4538531	NM_000222.3(KIT):c.2424T>G (p.Ile808Met)	KIT	Pathogenic	criteria provided, single submitter
565576	NM_000222.3(KIT):c.1861G>A (p.Ala621Thr)	KIT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098574	GRCh38/hg38 4q12-21.1(chr4:51891814-76009719)x1	TECRL	Pathogenic	criteria provided, single submitter
13849	NM_000222.3(KIT):c.1747G>A (p.Glu583Lys)	KIT	Likely pathogenic	criteria provided, single submitter
3899876	NM_000222.3(KIT):c.745_746del (p.Glu249fs)	KIT	Likely pathogenic	criteria provided, single submitter
3901185	NM_000222.3(KIT):c.1647G>C (p.Gln549His)	KIT	Likely pathogenic	criteria provided, single submitter
393590	NM_000222.3(KIT):c.2000T>G (p.Leu667Arg)	KIT	Likely pathogenic	criteria provided, single submitter
1333929	NM_000222.3(KIT):c.2244_2253del (p.Ile748fs)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134621	NM_000222.3(KIT):c.1588G>A (p.Val530Ile)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134627	NM_000222.3(KIT):c.2866C>T (p.Arg956Trp)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134629	NM_000222.3(KIT):c.1195G>A (p.Val399Ile)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1500519	NM_000222.3(KIT):c.1231+13A>T	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161259	NM_000222.3(KIT):c.532G>A (p.Ala178Thr)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161260	NM_000222.3(KIT):c.952A>G (p.Met318Val)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1694457	NM_000222.3(KIT):c.590C>T (p.Ser197Leu)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220634	NM_000222.3(KIT):c.1674G>A (p.Lys558=)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220917	NM_000222.3(KIT):c.2622G>A (p.Pro874=)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 21 · 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
KIT	Definitive	Autosomal dominant	piebaldism	15
SNAI2	Definitive	Autosomal dominant	piebaldism	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SNAI2	Orphanet:2884	Piebaldism
SNAI2	Orphanet:895	Waardenburg syndrome type 2
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans
KIT	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
KIT	Orphanet:98834	Acute myeloblastic leukemia with maturation
KIT	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
TECRL	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia

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
SNAI2	HGNC:11094	ENSG00000019549	O43623	Zinc finger protein SNAI2	gencc,clinvar
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	gencc,clinvar
CLOCK	HGNC:2082	ENSG00000134852	O15516	Circadian locomoter output cycles protein kaput	clinvar
TECRL	HGNC:27365	ENSG00000205678	Q5HYJ1	Trans-2,3-enoyl-CoA reductase-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SNAI2	Zinc finger protein SNAI2	Transcriptional repressor that modulates both activator-dependent and basal transcription.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
CLOCK	Circadian locomoter output cycles protein kaput	Transcriptional activator which forms a core component of the circadian clock.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 1 · 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
Kinase	1	6.9×	0.205
Transcription factor	2	4.1×	0.205
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SNAI2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf,
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
CLOCK	Transcription factor	no	2.3.1.48	PAS, Nuc_translocat, PAC
TECRL	Other/Unknown	no		3-oxo-5_a-steroid_4-DH_C, SRD5A/TECR, TECRL_Ubl

Expression context

Cohort genes with no expression data: 0.

3 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
oocyte	2
secondary oocyte	2
cartilage tissue	1
stromal cell of endometrium	1
tibia	1
lateral nuclear group of thalamus	1
germinal epithelium of ovary	1
heart right ventricle	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SNAI2	254	ubiquitous	marker	tibia, cartilage tissue, stromal cell of endometrium
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
CLOCK	294	ubiquitous	marker	secondary oocyte, oocyte, germinal epithelium of ovary
TECRL	135	tissue_specific	yes	myocardium, heart right ventricle, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIT	6,087
SNAI2	3,657
CLOCK	1,926
TECRL	814

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIT	P10721	52
CLOCK	O15516	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TECRL	Q5HYJ1	84.32
SNAI2	O43623	64.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Dasatinib-resistant KIT mutants	1	2855.0×	0.002	KIT
Imatinib-resistant KIT mutants	1	2855.0×	0.002	KIT
KIT mutants bind TKIs	1	2855.0×	0.002	KIT
Masitinib-resistant KIT mutants	1	2855.0×	0.002	KIT
Nilotinib-resistant KIT mutants	1	2855.0×	0.002	KIT
Regorafenib-resistant KIT mutants	1	2855.0×	0.002	KIT
Signaling by kinase domain mutants of KIT	1	2855.0×	0.002	KIT
Sunitinib-resistant KIT mutants	1	2855.0×	0.002	KIT
Signaling by juxtamembrane domain KIT mutants	1	2855.0×	0.002	KIT
Sorafenib-resistant KIT mutants	1	2855.0×	0.002	KIT
Drug resistance of KIT mutants	1	2855.0×	0.002	KIT
Signaling by extracellular domain mutants of KIT	1	2855.0×	0.002	KIT
Transcriptional and post-translational regulation of MITF-M expression and activity	2	89.2×	0.002	SNAI2, KIT
MITF-M-regulated melanocyte development	2	57.1×	0.002	SNAI2, KIT
Intracellular signaling by second messengers	2	45.7×	0.003	SNAI2, KIT
PIP3 activates AKT signaling	2	33.4×	0.005	SNAI2, KIT
Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK	1	571.0×	0.006	CLOCK
Signaling by KIT in disease	1	285.5×	0.011	KIT
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	1	219.6×	0.013	CLOCK
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	190.3×	0.015	KIT
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	178.4×	0.015	CLOCK
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	158.6×	0.015	KIT
Developmental Lineage of Mammary Gland Alveolar Cells	1	158.6×	0.015	KIT
Regulation of KIT signaling	1	150.3×	0.015	KIT
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	129.8×	0.017	KIT
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	1	119.0×	0.017	CLOCK
Synthesis of very long-chain fatty acyl-CoAs	1	114.2×	0.017	TECRL
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	114.2×	0.017	KIT
Fatty acyl-CoA biosynthesis	1	109.8×	0.018	TECRL
BMAL1:CLOCK,NPAS2 activates circadian expression	1	105.7×	0.018	CLOCK

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
pigmentation	2	351.1×	0.002	SNAI2, KIT
cellular response to ionizing radiation	2	205.5×	0.002	SNAI2, CLOCK
desmosome disassembly	1	4213.0×	0.005	SNAI2
melanocyte adhesion	1	4213.0×	0.005	KIT
positive regulation of pyloric antrum smooth muscle contraction	1	4213.0×	0.005	KIT
positive regulation of colon smooth muscle contraction	1	4213.0×	0.005	KIT
negative regulation of vitamin D receptor signaling pathway	1	2106.5×	0.005	SNAI2
positive regulation of vascular associated smooth muscle cell differentiation	1	2106.5×	0.005	KIT
photoperiodism	1	1404.3×	0.005	CLOCK
regulation of chemokine production	1	1404.3×	0.005	SNAI2
Fc receptor signaling pathway	1	1404.3×	0.005	KIT
Kit signaling pathway	1	1404.3×	0.005	KIT
regulation of branching involved in salivary gland morphogenesis	1	1404.3×	0.005	SNAI2
melanocyte migration	1	1404.3×	0.005	KIT
negative regulation of hematopoietic stem cell proliferation	1	1404.3×	0.005	SNAI2
obsolete regulation of bile acid metabolic process	1	1404.3×	0.005	KIT
positive regulation of small intestine smooth muscle contraction	1	1404.3×	0.005	KIT
mast cell chemotaxis	1	1053.2×	0.005	KIT
cell migration involved in endocardial cushion formation	1	1053.2×	0.005	SNAI2
negative regulation of cell adhesion involved in substrate-bound cell migration	1	1053.2×	0.005	SNAI2
negative regulation of vitamin D biosynthetic process	1	1053.2×	0.005	SNAI2
hematopoietic stem cell migration	1	1053.2×	0.005	KIT
mast cell differentiation	1	1053.2×	0.005	KIT
regulation of type B pancreatic cell development	1	1053.2×	0.005	CLOCK
positive regulation of dendritic cell cytokine production	1	842.6×	0.005	KIT
positive regulation of mast cell cytokine production	1	842.6×	0.005	KIT
cartilage morphogenesis	1	842.6×	0.005	SNAI2
mast cell proliferation	1	842.6×	0.005	KIT
positive regulation of mast cell proliferation	1	842.6×	0.005	KIT
lymphoid progenitor cell differentiation	1	702.2×	0.006	KIT

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) 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
KIT	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIT	99	4
SNAI2	0	0
CLOCK	0	0
TECRL	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
SUNITINIB	4	KIT
DASATINIB	4	KIT
ERLOTINIB	4	KIT
QUIZARTINIB	4	KIT
CRIZOTINIB	4	KIT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIT	2.7.10.1	receptor protein-tyrosine kinase
CLOCK	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KIT	2,305

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
SUNITINIB	4	KIT
DASATINIB	4	KIT
ERLOTINIB	4	KIT
QUIZARTINIB	4	KIT
CRIZOTINIB	4	KIT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KIT
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	SNAI2, CLOCK, TECRL

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)
SNAI2	0	—
CLOCK	0	—
TECRL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	3
PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01377077	PHASE4	UNKNOWN	Punchgrafting Techniques for Vitiligo
NCT01640678	PHASE4	UNKNOWN	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT02458417	PHASE4	COMPLETED	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT02156427	PHASE3	COMPLETED	Evaluation of Non-cultured Epidermal Cellular Grafting vs Hyaluronic Acid for Repigmenting Vitiligo and Piebaldism
NCT04919993	Not specified	COMPLETED	CBT for Insomnia in Primary Brain Tumor Patients