Hydrocephalus, nonsyndromic, autosomal recessive 1

Summary

Hydrocephalus, nonsyndromic, autosomal recessive 1 (MONDO:0009360) is a disease caused by CCDC88C (GenCC Strong), with 6 cohort genes.

At a glance

• Causal gene: CCDC88C (GenCC Strong)
• Cohort genes: 6
• ClinVar variants: 103

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hydrocephalus, nonsyndromic, autosomal recessive 1
Mondo ID	MONDO:0009360
OMIM	236600
UMLS	C3887608
MedGen	854455
GARD	0024663
Is cancer (heuristic)	no

Also known as: CCDC88C congenital hydrocephalus · congenital hydrocephalus caused by mutation in CCDC88C · HYC1 · hydrocephalus, congenital, 1 · hydrocephalus, nonsyndromic, autosomal recessive 1 · hydrocephalus, nonsyndromic, autosomal recessive type 1

Data availability: 103 ClinVar variants · 4 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 recessive disease › hydrocephalus, nonsyndromic, autosomal recessive 1

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

103 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 27 likely pathogenic, 11 conflicting classifications of pathogenicity, 9 benign, 9 benign/likely benign, 7 pathogenic, 5 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2956067	NM_001080414.4(CCDC88C):c.1420_1421del (p.Ser474fs)	CCDC88C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2957330	NM_001080414.4(CCDC88C):c.5101C>T (p.Arg1701Ter)	CCDC88C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2993938	NM_001080414.4(CCDC88C):c.5273_5276del (p.Thr1758fs)	CCDC88C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39860	NM_001080414.4(CCDC88C):c.5058+1G>A	CCDC88C	Pathogenic	no assertion criteria provided
39861	NM_001080414.4(CCDC88C):c.934C>T (p.Arg312Ter)	CCDC88C	Pathogenic	criteria provided, multiple submitters, no conflicts
4689143	NM_001080414.4(CCDC88C):c.3403C>T (p.Gln1135Ter)	CCDC88C	Pathogenic	criteria provided, single submitter
623482	NM_001080414.4(CCDC88C):c.5265_5266del (p.Phe1755fs)	CCDC88C	Pathogenic	no assertion criteria provided
918058	NM_001080414.4(CCDC88C):c.255dup (p.Lys86Ter)	CCDC88C	Pathogenic	criteria provided, single submitter
30178	NM_001395891.1(CLASP1):c.196-605C>T	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
599282	NM_001395891.1(CLASP1):c.196-594G>A	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4277807	NM_015221.4(DNMBP):c.2260+1G>A	DNMBP	Pathogenic	criteria provided, single submitter
2628091	NM_001145313.3(FSD1L):c.1411C>T (p.Gln471Ter)	FSD1L	Pathogenic	criteria provided, single submitter
2846535	NM_001080414.4(CCDC88C):c.4442-2A>G	CCDC88C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3067852	NM_001080414.4(CCDC88C):c.1597G>T (p.Glu533Ter)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3234949	NM_001080414.4(CCDC88C):c.3160C>T (p.Arg1054Ter)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576880	NM_001080414.4(CCDC88C):c.5250C>G (p.Tyr1750Ter)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576881	NM_001080414.4(CCDC88C):c.5132dup (p.Gln1712fs)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576882	NM_001080414.4(CCDC88C):c.4768+1G>T	CCDC88C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3576884	NM_001080414.4(CCDC88C):c.4113-1_4117del	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576885	NM_001080414.4(CCDC88C):c.4096G>T (p.Glu1366Ter)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576886	NM_001080414.4(CCDC88C):c.4090_4093delinsATT (p.His1364fs)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576887	NM_001080414.4(CCDC88C):c.3796del (p.His1266fs)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576889	NM_001080414.4(CCDC88C):c.3550G>T (p.Glu1184Ter)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576890	NM_001080414.4(CCDC88C):c.3358-2A>C	CCDC88C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3576891	NM_001080414.4(CCDC88C):c.3310del (p.Leu1104fs)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576892	NM_001080414.4(CCDC88C):c.3195+1G>T	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576893	NM_001080414.4(CCDC88C):c.3166_3167insT (p.Lys1056fs)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576895	NM_001080414.4(CCDC88C):c.3013A>T (p.Lys1005Ter)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576896	NM_001080414.4(CCDC88C):c.2903dup (p.Leu968fs)	CCDC88C	Likely pathogenic	criteria provided, single submitter
3576897	NM_001080414.4(CCDC88C):c.2206dup (p.Glu736fs)	CCDC88C	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · 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
CCDC88C	Strong	Autosomal recessive	hydrocephalus, nonsyndromic, autosomal recessive 1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCDC88C	Orphanet:269510	Congenital non-communicating hydrocephalus
CCDC88C	Orphanet:423275	Spinocerebellar ataxia type 40
DOCK6	Orphanet:974	Adams-Oliver syndrome
DNMBP	Orphanet:98994	Total early-onset cataract

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCDC88C	HGNC:19967	ENSG00000015133	Q9P219	Protein Daple	gencc,clinvar
FSD1L	HGNC:13753	ENSG00000106701	Q9BXM9	FSD1-like protein	clinvar
CLASP1	HGNC:17088	ENSG00000074054	Q7Z460	CLIP-associating protein 1	clinvar
DOCK6	HGNC:19189	ENSG00000130158	Q96HP0	Dedicator of cytokinesis protein 6	clinvar
DNAJC17	HGNC:25556	ENSG00000104129	Q9NVM6	DnaJ homolog subfamily C member 17	clinvar
DNMBP	HGNC:30373	ENSG00000107554	Q6XZF7	Dynamin-binding protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCDC88C	Protein Daple	Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling.
CLASP1	CLIP-associating protein 1	Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules.
DOCK6	Dedicator of cytokinesis protein 6	Acts as a guanine nucleotide exchange factor (GEF) for CDC42 and RAC1 small GTPases.
DNAJC17	DnaJ homolog subfamily C member 17	May negatively affect PAX8-induced thyroglobulin/TG transcription.
DNMBP	Dynamin-binding protein	Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.17

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
Antibody/Immunoglobulin	1	4.9×	0.451
Scaffold/PPI	1	2.9×	0.451
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CCDC88C	Other/Unknown	no		CH_dom, CH_dom_sf, HOOK_N
FSD1L	Antibody/Immunoglobulin	yes		B30.2/SPRY, Bbox_C, SPRY_dom
CLASP1	Other/Unknown	no		ARM-like, ARM-type_fold, HEAT_type_2
DOCK6	Other/Unknown	no		DOCK_C/D_N, DOCK, C2_DOCK-type_domain
DNAJC17	Other/Unknown	no		RRM_dom, DnaJ_domain, Nucleotide-bd_a/b_plait_sf
DNMBP	Scaffold/PPI	no		DH_dom, GDS_CDC24_CS, SH3_domain

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory segment of nasal mucosa	2
cortical plate	2
calcaneal tendon	2
granulocyte	1
right uterine tube	1
Brodmann (1909) area 23	1
endothelial cell	1
dorsal motor nucleus of vagus nerve	1
apex of heart	1
colonic epithelium	1
right lung	1
sural nerve	1
colonic mucosa	1
ileal mucosa	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDC88C	220	ubiquitous	marker	right uterine tube, granulocyte, olfactory segment of nasal mucosa
FSD1L	227	ubiquitous	marker	endothelial cell, cortical plate, Brodmann (1909) area 23
CLASP1	286	ubiquitous	marker	cortical plate, calcaneal tendon, dorsal motor nucleus of vagus nerve
DOCK6	254	ubiquitous	marker	colonic epithelium, right lung, apex of heart
DNAJC17	193	ubiquitous	marker	sural nerve, calcaneal tendon, olfactory segment of nasal mucosa
DNMBP	279	ubiquitous	marker	jejunal mucosa, ileal mucosa, colonic mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLASP1	1,686
DNAJC17	1,523
DNMBP	1,328
DOCK6	1,018
CCDC88C	906
FSD1L	324

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DOCK6	Q96HP0	7
DNMBP	Q6XZF7	7
CLASP1	Q7Z460	3
DNAJC17	Q9NVM6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FSD1L	Q9BXM9	85.09
CCDC88C	Q9P219	65.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 6 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
Negative regulation of TCF-dependent signaling by DVL-interacting proteins	1	571.0×	0.016	CCDC88C
CDC42 GTPase cycle	2	36.1×	0.016	DOCK6, DNMBP
Role of ABL in ROBO-SLIT signaling	1	317.2×	0.019	CLASP1
Loss of Nlp from mitotic centrosomes	1	39.6×	0.057	CLASP1
Loss of proteins required for interphase microtubule organization from the centrosome	1	39.6×	0.057	CLASP1
AURKA Activation by TPX2	1	38.1×	0.057	CLASP1
Recruitment of mitotic centrosome proteins and complexes	1	34.0×	0.057	CLASP1
Regulation of PLK1 Activity at G2/M Transition	1	31.7×	0.057	CLASP1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	29.1×	0.057	CLASP1
Recruitment of NuMA to mitotic centrosomes	1	29.1×	0.057	CLASP1
Anchoring of the basal body to the plasma membrane	1	28.3×	0.057	CLASP1
EML4 and NUDC in mitotic spindle formation	1	23.2×	0.063	CLASP1
Resolution of Sister Chromatid Cohesion	1	21.6×	0.063	CLASP1
RHO GTPases Activate Formins	1	19.4×	0.064	CLASP1
Mitotic Prometaphase	1	17.3×	0.064	CLASP1
Factors involved in megakaryocyte development and platelet production	1	16.6×	0.064	DOCK6
RAC1 GTPase cycle	1	15.3×	0.064	DOCK6
Separation of Sister Chromatids	1	15.2×	0.064	CLASP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
microtubule bundle formation	2	204.3×	9e-04	CCDC88C, CLASP1
negative regulation of microtubule depolymerization	2	198.3×	9e-04	CCDC88C, CLASP1
small GTPase-mediated signal transduction	2	73.3×	0.004	CCDC88C, DOCK6
spliceosomal complex disassembly	1	1685.2×	0.005	DNAJC17
respiratory basal cell differentiation	1	1685.2×	0.005	CCDC88C
negative regulation of microtubule polymerization or depolymerization	1	1123.5×	0.007	CLASP1
apical constriction	1	674.1×	0.009	CCDC88C
establishment of mitotic spindle localization	1	561.7×	0.010	CLASP1
negative regulation of wound healing, spreading of epidermal cells	1	481.5×	0.010	CLASP1
establishment of spindle orientation	1	421.3×	0.010	CLASP1
obsolete vesicle targeting	1	337.0×	0.011	CLASP1
microtubule organizing center organization	1	280.9×	0.011	CLASP1
astral microtubule organization	1	259.3×	0.011	CLASP1
microtubule anchoring	1	259.3×	0.011	CLASP1
mucociliary clearance	1	259.3×	0.011	CCDC88C
positive regulation of extracellular matrix disassembly	1	240.7×	0.011	CLASP1
exit from mitosis	1	210.7×	0.012	CLASP1
cytoskeleton-dependent intracellular transport	1	187.2×	0.013	CCDC88C
positive regulation of microtubule polymerization	1	134.8×	0.015	CLASP1
microtubule nucleation	1	124.8×	0.015	CLASP1
cilium organization	1	120.4×	0.015	CCDC88C
positive regulation of exocytosis	1	120.4×	0.015	CLASP1
regulation of focal adhesion assembly	1	120.4×	0.015	CLASP1
non-canonical Wnt signaling pathway	1	116.2×	0.015	CCDC88C
negative regulation of stress fiber assembly	1	116.2×	0.015	CLASP1
regulation of Rho protein signal transduction	1	102.1×	0.016	DOCK6
basement membrane organization	1	102.1×	0.016	CLASP1
Wnt signaling pathway, planar cell polarity pathway	1	91.1×	0.017	CCDC88C
positive regulation of epithelial cell migration	1	82.2×	0.018	CLASP1
establishment or maintenance of cell polarity	1	80.2×	0.018	CLASP1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 2 of 6 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCDC88C	0	0
FSD1L	0	0
CLASP1	0	0
DOCK6	0	0
DNAJC17	0	0
DNMBP	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
CLASP1	10	Binding:10
DNMBP	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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	1	FSD1L
E	Difficult family or no structure, no drug	5	CCDC88C, CLASP1, DOCK6, DNAJC17, DNMBP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CCDC88C	0	—
FSD1L	0	—
CLASP1	10	—
DOCK6	0	—
DNAJC17	0	—
DNMBP	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.