McKusick-Kaufman syndrome

Summary

McKusick-Kaufman syndrome (MONDO:0009367) is a disease caused by MKKS (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: MKKS (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 539
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		90	Worldwide	Validated
Prevalence at birth	1-5 / 10 000	10	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0030010	Hydrometrocolpos	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000126	Hydronephrosis	Frequent (30-79%)
HP:0000807	Glandular hypospadias	Frequent (30-79%)
HP:0001162	Postaxial hand polydactyly	Frequent (30-79%)
HP:0100779	Urogenital sinus anomaly	Frequent (30-79%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0001156	Brachydactyly	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001830	Postaxial foot polydactyly	Occasional (5-29%)
HP:0002023	Anal atresia	Occasional (5-29%)
HP:0002251	Aganglionic megacolon	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0004383	Hypoplastic left heart	Occasional (5-29%)
HP:0004397	Ectopic anus	Occasional (5-29%)
HP:0005916	Abnormal metacarpal morphology	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0008368	Tarsal synostosis	Occasional (5-29%)
HP:0012227	Urethral stricture	Occasional (5-29%)
HP:0008678	Renal hypoplasia/aplasia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	McKusick-Kaufman syndrome
Mondo ID	MONDO:0009367
MeSH	C538159
OMIM	236700
Orphanet	2473
DOID	DOID:0111255
SNOMED CT	702407009
UMLS	C0948368
MedGen	184924
GARD	0003427
MedDRA	10052312
Is cancer (heuristic)	no

Also known as: HMCS · hydrometrocolpos-postaxial polydactyly syndrome · Kaufman McKusick syndrome · Kaufman-Mckusick syndrome · McKusick Kaufman syndrome · McKusick-Kaufman syndrome · MKKS

Data availability: 539 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome without intellectual disability › McKusick-Kaufman syndrome

Related subtypes (167): Treacher-Collins syndrome, branchio-oto-renal syndrome, acrorenal syndrome, Townes-Brocks syndrome, Ascher syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, branchiooculofacial syndrome, Gordon syndrome, cataract-aberrant oral frenula-growth delay syndrome, cherubism, Alagille syndrome, cleft palate-lateral synechia syndrome, blepharocheilodontic syndrome, craniofacial-deafness-hand syndrome, cryptomicrotia-brachydactyly-excess fingertip arch syndrome, Beare-Stevenson cutis gyrata syndrome, Cyprus facial-neuromusculoskeletal syndrome, deafness-craniofacial syndrome, short stature-valvular heart disease-characteristic facies syndrome, 3-M syndrome, external auditory canal atresia-vertical talus-hypertelorism syndrome, femoral-facial syndrome, multinodular goiter-cystic kidney-polydactyly syndrome, hand-foot-genital syndrome, Bencze syndrome, oculoauriculovertebral spectrum with radial defects, Holt-Oram syndrome, mullerian duct anomalies-limb anomalies syndrome, Aase-Smith syndrome, LADD syndrome, Noonan syndrome with multiple lentigines, median nodule of the upper lip, Nager acrofacial dysostosis, Marshall syndrome, Binder syndrome, Schilbach-Rott syndrome, nasopalpebral lipoma-coloboma syndrome, autosomal dominant prognathism, short stature-craniofacial anomalies-genital hypoplasia syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, scalp-ear-nipple syndrome, flat face-microstomia-ear anomaly syndrome, Czeizel-Losonci syndrome, otospondylomegaepiphyseal dysplasia, autosomal dominant, ventricular extrasystoles with syncopal episodes-perodactyly-robin sequence syndrome, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, acrofacial dysostosis, Weyers type, Freeman-Sheldon syndrome, Ackerman syndrome, acro-renal-mandibular syndrome, acrocraniofacial dysostosis, PAGOD syndrome, alar cartilages hypoplasia-coloboma-telecanthus syndrome, microcephaly-albinism-digital anomalies syndrome, fetal akinesia deformation sequence, Cooper-Jabs syndrome, Barber-Say syndrome, Beemer-Ertbruggen syndrome, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, camptodactyly syndrome, Guadalajara type 1, camptodactyly syndrome, Guadalajara type 2, heart defects-limb shortening syndrome, Verloove Vanhorick-Brubakk syndrome, Juberg-Hayward syndrome, heart defect - tongue hamartoma - polysyndactyly syndrome, Fraser syndrome, split hand-foot malformation 1 with sensorineural hearing loss, von Voss-Cherstvoy syndrome, autosomal recessive faciodigitogenital syndrome, gingival fibromatosis-facial dysmorphism syndrome, Fibulo-ulnar hypoplasia-renal anomalies syndrome, frontofacionasal dysplasia, genito-palato-cardiac syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Holzgreve-Wagner-Rehder syndrome, hydrocephaly-tall stature-joint laxity syndrome, acrofrontofacionasal dysostosis 2, Vici syndrome, Donohue syndrome, Dahlberg-Borer-Newcomer syndrome, macrosomia-microphthalmia-cleft palate syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, Nijmegen breakage syndrome, lethal congenital contracture syndrome 1, Richieri Costa-da Silva syndrome, Keipert syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, ichthyosis-oral and digital anomalies syndrome, otoonychoperoneal syndrome, PHAVER syndrome, polysyndactyly-cardiac malformation syndrome, postaxial acrofacial dysostosis, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, renal-genital-middle ear anomalies, Richieri Costa-Pereira syndrome, SHORT syndrome, tetraamelia-multiple malformations syndrome, thymic-renal-anal-lung dysplasia, trigonocephaly-bifid nose-acral anomalies syndrome, white forelock with malformations, syndactyly-telecanthus-anogenital and renal malformations syndrome, Abruzzo-Erickson syndrome, CHILD syndrome, pentalogy of Cantrell, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, short tarsus-absence of lower eyelashes syndrome, PARC syndrome, CODAS syndrome, pectus excavatum-macrocephaly-dysplastic nails syndrome, velo-facial-skeletal syndrome, anophthalmia plus syndrome, van den Ende-Gupta syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, diaphragmatic defect-limb deficiency-skull defect syndrome, cleft lip/palate-intestinal malrotation-cardiopathy syndrome, Matthew-Wood syndrome, microcephaly-cardiac defect-lung malsegmentation syndrome, dislocation of the hip-dysmorphism syndrome, short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome, grange syndrome, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, arhinia, choanal atresia, and microphthalmia, anonychia-microcephaly syndrome, developmental malformations-deafness-dystonia syndrome, lethal congenital contracture syndrome 2, craniolenticulosutural dysplasia, 8q22.1 microdeletion syndrome, Braddock syndrome, choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome, BNAR syndrome, Frias syndrome, lethal congenital contracture syndrome 3, Fontaine progeroid syndrome, microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type, Nijmegen breakage syndrome-like disorder, Warsaw breakage syndrome, even-plus syndrome, split-foot malformation-mesoaxial polydactyly syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, digitotalar dysmorphism, heart-hand syndrome type 2, night blindness-skeletal anomalies-dysmorphism syndrome, Charlie M syndrome, facial dysmorphism-anorexia-cachexia-eye and skin anomalies syndrome, cleft lip-retinopathy syndrome, Cole-Carpenter syndrome, progressive non-infectious anterior vertebral fusion, dysmorphism-pectus carinatum-joint laxity syndrome, Hirschsprung disease-type D brachydactyly syndrome, mandibuloacral dysplasia, contractures - webbed neck - micrognathia - hypoplastic nipples syndrome, Thomas syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, branchiootic syndrome, auricular abnormalities-cleft lip with or without cleft palate-ocular abnormalities syndrome, Axenfeld-Rieger syndrome, macrostomia-preauricular tags-external ophthalmoplegia syndrome, pelvis syndrome, Fanconi anemia, van der Woude syndrome, hypertrichosis-acromegaloid facial appearance syndrome, 49,XYYYY syndrome, congenital vertebral-cardiac-renal anomalies syndrome, structural heart defects and renal anomalies syndrome, Greig cephalopolysyndactyly-contiguous gene 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

539 retrieved; paginated sample, class counts are floors:

209 uncertain significance, 205 likely benign, 39 pathogenic, 31 conflicting classifications of pathogenicity, 29 pathogenic/likely pathogenic, 10 likely pathogenic, 9 benign, 7 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
448914	NM_170784.2(MKKS):c.[250C>T;724G>T]		Pathogenic	no assertion criteria provided
1066030	NM_170784.3(MKKS):c.1034G>A (p.Gly345Glu)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074439	NM_170784.3(MKKS):c.63_64del (p.Arg21fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179069	NM_170784.3(MKKS):c.986-1G>A	MKKS	Pathogenic	criteria provided, multiple submitters, no conflicts
1297700	NM_170784.3(MKKS):c.1436C>G (p.Ser479Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1379642	NM_170784.3(MKKS):c.889dup (p.Ile297fs)	MKKS	Pathogenic	criteria provided, single submitter
1406457	NM_170784.3(MKKS):c.867dup (p.Leu290fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1408352	NM_170784.3(MKKS):c.676C>T (p.Gln226Ter)	MKKS	Pathogenic	criteria provided, single submitter
1408644	NM_170784.3(MKKS):c.375_381dup (p.Ile128fs)	MKKS	Pathogenic	criteria provided, single submitter
1431638	NM_170784.3(MKKS):c.940_941del (p.Asp314fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1433005	NM_170784.3(MKKS):c.763dup (p.Thr255fs)	MKKS	Pathogenic	criteria provided, single submitter
1439776	NM_170784.3(MKKS):c.1291_1337del (p.Ser431fs)	MKKS	Pathogenic	criteria provided, single submitter
1450424	NM_170784.3(MKKS):c.1013C>A (p.Ser338Ter)	MKKS	Pathogenic	criteria provided, single submitter
1455389	NM_170784.3(MKKS):c.175_176del (p.Gln59fs)	MKKS	Pathogenic	criteria provided, single submitter
1455421	NM_170784.3(MKKS):c.97del (p.Ile32_Val33insTer)	MKKS	Pathogenic	criteria provided, single submitter
1457348	NM_170784.3(MKKS):c.1181del (p.Leu394fs)	MKKS	Pathogenic	criteria provided, single submitter
1457941	NM_170784.3(MKKS):c.515_516del (p.Glu172fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1683700	NM_170784.3(MKKS):c.429_434delinsTT (p.Phe144fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1712273	NM_170784.3(MKKS):c.950_960del (p.Gly317fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2031791	NM_170784.3(MKKS):c.221del (p.Ile73_Leu74insTer)	MKKS	Pathogenic	criteria provided, single submitter
2056365	NM_170784.3(MKKS):c.432dup (p.Ser145Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2119610	NM_170784.3(MKKS):c.1149G>A (p.Trp383Ter)	MKKS	Pathogenic	criteria provided, single submitter
2154926	NM_170784.3(MKKS):c.1272+2T>C	MKKS	Pathogenic	criteria provided, single submitter
2158742	NM_170784.3(MKKS):c.942_945del (p.Asp314fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2415952	NM_170784.3(MKKS):c.1118del (p.Leu373fs)	MKKS	Pathogenic	criteria provided, single submitter
2629959	NM_170784.3(MKKS):c.1148G>A (p.Trp383Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676533	NM_170784.3(MKKS):c.221T>G (p.Leu74Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676536	NM_170784.3(MKKS):c.1410_1413del (p.Thr470_Asp471insTer)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676539	NM_170784.3(MKKS):c.966del (p.Glu322fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676540	NM_170784.3(MKKS):c.1434G>A (p.Trp478Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 5 · 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
MKKS	Definitive	Autosomal recessive	McKusick-Kaufman syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MKKS	Orphanet:110	Bardet-Biedl syndrome
MKKS	Orphanet:2473	McKusick-Kaufman syndrome
JAG1	Orphanet:261600	Alagille syndrome due to 20p12 microdeletion
JAG1	Orphanet:261619	Alagille syndrome due to a JAG1 point mutation
JAG1	Orphanet:3303	Tetralogy of Fallot

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MKKS	HGNC:7108	ENSG00000125863	Q9NPJ1	Molecular chaperone MKKS	gencc,clinvar
JAG1	HGNC:6188	ENSG00000101384	P78504	Protein jagged-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MKKS	Molecular chaperone MKKS	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
JAG1	Protein jagged-1	Ligand for multiple Notch receptors and involved in the mediation of Notch signaling.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MKKS	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
JAG1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, VWF_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
middle temporal gyrus	1
prefrontal cortex	1
blood vessel layer	1
skin of hip	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MKKS	277	ubiquitous	marker	middle temporal gyrus, endothelial cell, prefrontal cortex
JAG1	297	ubiquitous	marker	upper leg skin, skin of hip, blood vessel layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
JAG1	4,405
MKKS	2,728

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
JAG1	P78504	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MKKS	Q9NPJ1	89.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

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

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	1427.5×	0.011	JAG1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	815.7×	0.011	JAG1
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	634.4×	0.011	JAG1
NOTCH4 Activation and Transmission of Signal to the Nucleus	1	519.1×	0.011	JAG1
Nephron development	1	439.2×	0.011	JAG1
RUNX3 regulates NOTCH signaling	1	407.9×	0.011	JAG1
Kidney development	1	407.9×	0.011	JAG1
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	380.7×	0.011	JAG1
Signaling by NOTCH2	1	356.9×	0.011	JAG1
Signaling by NOTCH3	1	259.6×	0.011	JAG1
BBSome-mediated cargo-targeting to cilium	1	248.3×	0.011	MKKS
Signaling by NOTCH4	1	248.3×	0.011	JAG1
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	237.9×	0.011	JAG1
NOTCH2 Activation and Transmission of Signal to the Nucleus	1	219.6×	0.011	JAG1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1	203.9×	0.011	JAG1
Signaling by NOTCH1 in Cancer	1	203.9×	0.011	JAG1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1	203.9×	0.011	JAG1
Signaling by NOTCH1	1	178.4×	0.011	JAG1
Activated NOTCH1 Transmits Signal to the Nucleus	1	178.4×	0.011	JAG1
Transcriptional regulation by RUNX3	1	135.9×	0.014	JAG1
Cargo trafficking to the periciliary membrane	1	124.1×	0.015	MKKS
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	98.5×	0.017	JAG1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	98.5×	0.017	JAG1
Signaling by NOTCH	1	87.8×	0.018	JAG1
RAC3 GTPase cycle	1	59.5×	0.025	JAG1
Cilium Assembly	1	54.4×	0.027	MKKS
Organelle biogenesis and maintenance	1	33.0×	0.042	MKKS
RAC1 GTPase cycle	1	30.5×	0.043	JAG1
RHO GTPase cycle	1	30.1×	0.043	JAG1
Diseases of signal transduction by growth factor receptors and second messengers	1	28.4×	0.044	JAG1

GO biological processes by enrichment

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

GO term	Cohort genes	Fold	FDR	Sample cohort genes
endocardial cushion cell development	1	8426.0×	0.003	JAG1
pigment granule aggregation in cell center	1	4213.0×	0.003	MKKS
convergent extension involved in gastrulation	1	4213.0×	0.003	MKKS
loop of Henle development	1	4213.0×	0.003	JAG1
cardiac neural crest cell development involved in outflow tract morphogenesis	1	2808.7×	0.003	JAG1
distal tubule development	1	2808.7×	0.003	JAG1
inhibition of neuroepithelial cell differentiation	1	2106.5×	0.003	JAG1
negative regulation of appetite by leptin-mediated signaling pathway	1	2106.5×	0.003	MKKS
ciliary body morphogenesis	1	2106.5×	0.003	JAG1
positive regulation of cardiac epithelial to mesenchymal transition	1	2106.5×	0.003	JAG1
response to inositol	1	2106.5×	0.003	MKKS
negative regulation of endothelial cell differentiation	1	1685.2×	0.004	JAG1
positive regulation of myeloid cell differentiation	1	1685.2×	0.004	JAG1
pulmonary artery morphogenesis	1	1404.3×	0.004	JAG1
neuroendocrine cell differentiation	1	1203.7×	0.004	JAG1
artery smooth muscle contraction	1	936.2×	0.005	MKKS
regulation of cilium beat frequency involved in ciliary motility	1	936.2×	0.005	MKKS
nephron development	1	936.2×	0.005	JAG1
morphogenesis of an epithelial sheet	1	842.6×	0.005	JAG1
podocyte development	1	766.0×	0.005	JAG1
cardiac right ventricle morphogenesis	1	702.2×	0.005	JAG1
response to muramyl dipeptide	1	702.2×	0.005	JAG1
inner ear auditory receptor cell differentiation	1	601.9×	0.005	JAG1
cardiac septum morphogenesis	1	601.9×	0.005	JAG1
gonad development	1	561.7×	0.005	MKKS
striatum development	1	561.7×	0.005	MKKS
endothelial cell differentiation	1	561.7×	0.005	JAG1
T cell mediated immunity	1	495.6×	0.005	JAG1
negative regulation of cell-cell adhesion	1	495.6×	0.005	JAG1
regulation of stress fiber assembly	1	495.6×	0.005	MKKS

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MKKS	0	0
JAG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
JAG1	1	Binding:1

Pharmacogenomics

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

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

Chemical tractability of cohort targets

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):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	2	MKKS, JAG1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MKKS	0	—
JAG1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.