Cooks syndrome

Summary

Cooks syndrome (MONDO:0007134) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 8

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		12	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

8 HPO clinical features (Orphanet curated; top 8 by frequency):

HPO ID	Term	Frequency
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0001171	Split hand	Very frequent (80-99%)
HP:0001199	Triphalangeal thumb	Very frequent (80-99%)
HP:0001810	Dystrophic toenail	Very frequent (80-99%)
HP:0008391	Dystrophic fingernails	Very frequent (80-99%)
HP:0010624	Aplastic/hypoplastic toenail	Very frequent (80-99%)
HP:0011304	Broad thumb	Very frequent (80-99%)
HP:0008388	Abnormal toenail morphology	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Cooks syndrome
Mondo ID	MONDO:0007134
MeSH	C537766
OMIM	106995
Orphanet	1487
SNOMED CT	720747002
UMLS	C1862841
MedGen	354848
GARD	0004083
Is cancer (heuristic)	no

Also known as: anonychia and absence/hypoplasia of distal phalanges · anonychia-onychodystrophy with hypoplasia or absence of distal phalanges syndrome · Cooks syndrome · ODP

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › dysostosis › Cooks syndrome

Related subtypes (107): trigonocephaly, spondylocostal dysostosis, synostosis, Adams-Oliver syndrome, adactylia, unilateral, ADULT syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, brachydactyly-arterial hypertension syndrome, fibular aplasia-ectrodactyly syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, congenital pseudoarthrosis of clavicle, external auditory canal atresia-vertical talus-hypertelorism syndrome, femoral-facial syndrome, hand-foot-genital syndrome, oculoauriculovertebral spectrum with radial defects, IVIC syndrome, nail-patella syndrome, patella aplasia/hypoplasia, pelvis-shoulder dysplasia, phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome, postaxial tetramelic oligodactyly, Currarino triad, radio-renal syndrome, splenogonadal fusion-limb defects-micrognathia syndrome, Karsch-Neugebauer syndrome, tetramelic monodactyly, tibia, hypoplasia or aplasia of, with polydactyly, humerus trochlea aplasia, Aphalangy-hemivertebrae-urogenital-intestinal dysgenesis syndrome, camptodactyly syndrome, Guadalajara type 2, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, split hand-foot malformation 1 with sensorineural hearing loss, EEM syndrome, lethal faciocardiomelic dysplasia, femur-fibula-ulna complex, Gollop-Wolfgang complex, acromesomelic dysplasia 2B, Fuhrmann syndrome, absence deformity of leg-cataract syndrome, intellectual disability-spasticity-ectrodactyly syndrome, fibular aplasia, tibial campomelia, and oligosyndactyly syndrome, otoonychoperoneal syndrome, pelviscapular dysplasia, rapadilino syndrome, EEC syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, tetraamelia-multiple malformations syndrome, thrombocytopenia-absent radius syndrome, phocomelia, Schinzel type, ulna hypoplasia-intellectual disability syndrome, absent radius-anogenital anomalies syndrome, ulnar hypoplasia-split foot syndrome, aphalangy-syndactyly-microcephaly syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, autosomal recessive amelia, pelvic dysplasia-arthrogryposis of lower limbs syndrome, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, genitopatellar syndrome, Duane-radial ray syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, camptodactyly syndrome, Guadalajara type 3, mammary-digital-nail syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, split-foot malformation-mesoaxial polydactyly syndrome, amniotic band syndrome, radial deficiency-tibial hypoplasia syndrome, mandibulofacial dysostosis, oromandibular-limb anomalies syndrome, congenital pseudoarthrosis of the limbs, oculomaxillofacial dysostosis, shoulder and thorax deformity-congenital heart disease syndrome, femoral agenesis/hypoplasia, progressive non-infectious anterior vertebral fusion, hemimelia, heart-hand syndrome, split hand-foot malformation, Melhem-Fahl syndrome, limb transversal defect-cardiac anomaly syndrome, frontonasal dysplasia, imperforate oropharynx-costo vetebral anomalies syndrome, non-syndromic amelia, congenital absence of upper arm and forearm with hand present, congenital absence of thigh and lower leg with foot present, congenital absence of both forearm and hand, congenital absence of both lower leg and foot, acheiria, apodia, split hand, split foot, hyperphalangy, Prata-Liberal-Goncalves syndrome, syngnathia multiple anomalies, hereditary thrombocytosis with transverse limb defect, thalidomide embryopathy, tibial aplasia-ectrodactyly syndrome, bipartite talus, acrofacial dysostosis, adactyly of foot, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, Rubinstein-Taybi syndrome, ischio-vertebral syndrome, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, preaxial digit brachydactyly-webbed fingers, proximal femoral focal deficiency, dysostosis multiplex, Ain-Naz type

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
SOX9	Limited	Autosomal dominant	Cooks syndrome	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX9	Orphanet:140	Campomelic dysplasia
SOX9	Orphanet:2138	46,XX ovotesticular difference of sex development
SOX9	Orphanet:242	46,XY complete gonadal dysgenesis
SOX9	Orphanet:251510	46,XY partial gonadal dysgenesis
SOX9	Orphanet:393	46,XX testicular difference of sex development
SOX9	Orphanet:718	Isolated Pierre Robin sequence

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cranial nerve II	1
hair follicle	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOX9	274	ubiquitous	marker	ventricular zone, cranial nerve II, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOX9	4,935

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOX9	P48436	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional regulation of testis differentiation	1	713.8×	0.010	SOX9
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.010	SOX9
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.010	SOX9
Transcriptional regulation by RUNX2	1	253.8×	0.010	SOX9
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.010	SOX9
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.010	SOX9
Developmental Cell Lineages	1	223.9×	0.010	SOX9
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.011	SOX9
TCF dependent signaling in response to WNT	1	117.7×	0.013	SOX9
MITF-M-regulated melanocyte development	1	114.2×	0.013	SOX9
Signaling by WNT	1	112.0×	0.013	SOX9
RNA Polymerase II Transcription	1	22.5×	0.059	SOX9
Gene expression (Transcription)	1	17.8×	0.069	SOX9
Generic Transcription Pathway	1	15.1×	0.074	SOX9
Developmental Biology	1	14.5×	0.074	SOX9
Signal Transduction	1	10.2×	0.098	SOX9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of immune system process	1	8426.0×	0.001	SOX9
epithelial cell proliferation involved in prostatic bud elongation	1	8426.0×	0.001	SOX9
regulation of cell proliferation involved in tissue homeostasis	1	8426.0×	0.001	SOX9
regulation of branching involved in lung morphogenesis	1	8426.0×	0.001	SOX9
cell proliferation involved in heart morphogenesis	1	8426.0×	0.001	SOX9
regulation of epithelial cell proliferation involved in lung morphogenesis	1	8426.0×	0.001	SOX9
heart valve formation	1	5617.3×	0.001	SOX9
neural crest cell fate specification	1	5617.3×	0.001	SOX9
male germ-line sex determination	1	5617.3×	0.001	SOX9
intrahepatic bile duct development	1	5617.3×	0.001	SOX9
bronchus cartilage development	1	5617.3×	0.001	SOX9
lung smooth muscle development	1	5617.3×	0.001	SOX9
ureter urothelium development	1	5617.3×	0.001	SOX9
ureter smooth muscle cell differentiation	1	5617.3×	0.001	SOX9
negative regulation of beta-catenin-TCF complex assembly	1	5617.3×	0.001	SOX9
glial cell fate specification	1	4213.0×	0.001	SOX9
cellular response to heparin	1	4213.0×	0.001	SOX9
renal vesicle induction	1	4213.0×	0.001	SOX9
positive regulation of kidney development	1	4213.0×	0.001	SOX9
chondrocyte hypertrophy	1	3370.4×	0.001	SOX9
growth plate cartilage chondrocyte growth	1	3370.4×	0.001	SOX9
astrocyte fate commitment	1	3370.4×	0.001	SOX9
trachea cartilage development	1	3370.4×	0.001	SOX9
morphogenesis of a branching epithelium	1	3370.4×	0.001	SOX9
Harderian gland development	1	3370.4×	0.001	SOX9
metanephric nephron tubule formation	1	3370.4×	0.001	SOX9
positive regulation of cell proliferation involved in heart morphogenesis	1	3370.4×	0.001	SOX9
chondrocyte differentiation involved in endochondral bone morphogenesis	1	2808.7×	0.002	SOX9
anterior head development	1	2808.7×	0.002	SOX9
negative regulation of photoreceptor cell differentiation	1	2407.4×	0.002	SOX9

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SOX9	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
SOX9	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	SOX9

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SOX9	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.