Hydrocephalus

Summary

Hydrocephalus (MONDO:0001150) is a disease (an umbrella term covering 7 Mondo subtypes) with 17 cohort genes and 125 clinical trials. Top therapeutic interventions include glycopyrronium, entecavir, and isoflurane.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 17
• ClinVar variants: 23
• Clinical trials: 125

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hydrocephalus
Mondo ID	MONDO:0001150
MeSH	D006849
DOID	DOID:10908
ICD-10-CM	G91
ICD-11	574533444
NCIT	C3111
SNOMED CT	230745008
UMLS	C0020255
MedGen	9335
Is cancer (heuristic)	no

Also known as: hydrocephalus, nonsyndromic, autosomal recessive · hydrocephalus, X-linked

Data availability: 23 ClinVar variants.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › hydrocephalus

Related subtypes (70): leukoencephalopathy, megalencephalic, encephalopathy, acute, infection-induced, diabetic encephalopathy, complex cortical dysplasia with other brain malformations, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, migraine disorder, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, brain edema, encephalomalacia, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, insomnia, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cluster headache syndrome, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

Subtypes (7): obstructive hydrocephalus, communicating hydrocephalus, craniosynostosis-Dandy-Walker malformation-hydrocephalus syndrome, congenital hydrocephalus, megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome, baker Vinters syndrome, palmer pagon 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

23 retrieved; paginated sample, class counts are floors:

10 pathogenic, 4 uncertain significance, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
694603	NCBI36/hg18 9q22.32-22.33(chr9:95946863-99986314)x1		Pathogenic	no assertion criteria provided
1703611	GRCh37/hg19 16p13.11(chr16:14899676-16516109)	ABCC1	Pathogenic	no assertion criteria provided
1703663	GRCh37/hg19 6q25.3-27(chr6:159121459-170919482)	ACAT2	Pathogenic	no assertion criteria provided
183282	NM_006420.3(ARFGEF2):c.656dup (p.Val220fs)	ARFGEF2	Pathogenic	criteria provided, single submitter
183349	NM_001384125.1(BLTP1):c.1557T>A (p.Tyr519Ter)	BLTP1	Pathogenic	criteria provided, single submitter
523437	NM_001372.4(DNAH9):c.308dup (p.Leu104fs)	DNAH9	Pathogenic	criteria provided, multiple submitters, no conflicts
183359	NM_001383.6(DPH1):c.686T>C (p.Leu229Pro)	DPH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13271	NM_000141.5(FGFR2):c.1040C>G (p.Ser347Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1251992	NM_024926.4(IFT56):c.4-1G>C	IFT56	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375682	NM_002609.4(PDGFRB):c.1696T>C (p.Trp566Arg)	PDGFRB	Pathogenic	criteria provided, multiple submitters, no conflicts
374077	NM_000302.4(PLOD1):c.1562G>A (p.Trp521Ter)	PLOD1	Pathogenic	criteria provided, single submitter
523237	GRCh37/hg19 1p36.22(chr1:12019879-12028775)	PLOD1	Pathogenic	criteria provided, single submitter
1180732	NM_017739.4(POMGNT1):c.74G>A (p.Trp25Ter)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
632606	NM_017412.4(FZD3):c.1616dup (p.Asp539fs)	FZD3	Likely pathogenic	no assertion criteria provided
632604	NM_012310.5(KIF4A):c.794G>T (p.Arg265Leu)	KIF4A	Likely pathogenic	no assertion criteria provided
183319	NM_002508.3(NID1):c.3385+1G>A	NID1	Likely pathogenic	no assertion criteria provided
183355	NM_153229.3(TMEM92):c.95+3A>G	TMEM92	Likely pathogenic	no assertion criteria provided
587642	NM_001080414.4(CCDC88C):c.5251G>A (p.Val1751Ile)	CCDC88C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
451447	NM_020822.3(KCNT1):c.1407C>G (p.His469Gln)	KCNT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267797	46;XX;inv(2)(p11q13)dn		Uncertain significance	criteria provided, single submitter
267862	46;XY;t(1;3)(p22;q21)dn		Uncertain significance	criteria provided, single submitter
587522	NM_001080414.4(CCDC88C):c.3539G>A (p.Arg1180Gln)	CCDC88C	Uncertain significance	criteria provided, single submitter
1236184	NM_001372.4(DNAH9):c.5651G>C (p.Gly1884Ala)	DNAH9	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 37 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARFGEF2	Orphanet:98892	Periventricular nodular heterotopia
KCNT1	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
KCNT1	Orphanet:98784	Sleep-related hypermotor epilepsy
POMGNT1	Orphanet:206564	POMGNT1-related limb-girdle muscular dystrophy R15
POMGNT1	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
POMGNT1	Orphanet:588	Muscle-eye-brain disease
POMGNT1	Orphanet:791	Retinitis pigmentosa
POMGNT1	Orphanet:899	Walker-Warburg syndrome
CCDC88C	Orphanet:269510	Congenital non-communicating hydrocephalus
CCDC88C	Orphanet:423275	Spinocerebellar ataxia type 40
BLTP1	Orphanet:610569	KIAA1109-related early lethal congenital brain malformations-arthrogryposis syndrome
DNAH9	Orphanet:101063	Situs inversus totalis
DNAH9	Orphanet:157769	Situs ambiguus
DNAH9	Orphanet:244	Primary ciliary dyskinesia
DPH1	Orphanet:459061	Craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3
ABCC1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
NID1	Orphanet:269215	Isolated Dandy-Walker malformation without hydrocephalus
PDGFRB	Orphanet:168950	Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement
PDGFRB	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFRB	Orphanet:2591	Infantile myofibromatosis
PDGFRB	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRB	Orphanet:363665	Acroosteolysis-keloid-like lesions-premature aging syndrome
PDGFRB	Orphanet:477831	Kosaki overgrowth syndrome
PDGFRB	Orphanet:86830	Chronic myeloproliferative disease, unclassifiable
PLOD1	Orphanet:1900	Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency

Cohort genes → proteins

17 cohort genes, 17 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	17

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KIF4A	HGNC:13339	ENSG00000090889	O95239	Chromosome-associated kinesin KIF4A	clinvar
ARFGEF2	HGNC:15853	ENSG00000124198	Q9Y6D5	Brefeldin A-inhibited guanine nucleotide-exchange protein 2	clinvar
KCNT1	HGNC:18865	ENSG00000107147	Q5JUK3	Potassium channel subfamily T member 1	clinvar
POMGNT1	HGNC:19139	ENSG00000085998	Q8WZA1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	clinvar
CCDC88C	HGNC:19967	ENSG00000015133	Q9P219	Protein Daple	clinvar
IFT56	HGNC:21882	ENSG00000105948	A0AVF1	Intraflagellar transport protein 56	clinvar
TMEM92	HGNC:26579	ENSG00000167105	Q6UXU6	Transmembrane protein 92	clinvar
BLTP1	HGNC:26953	ENSG00000138688	Q2LD37	Bridge-like lipid transfer protein family member 1	clinvar
DNAH9	HGNC:2953	ENSG00000007174	Q9NYC9	Dynein axonemal heavy chain 9	clinvar
DPH1	HGNC:3003	ENSG00000108963	Q9BZG8	2-(3-amino-3-carboxypropyl)histidine synthase subunit 1	clinvar
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	clinvar
FZD3	HGNC:4041	ENSG00000104290	Q9NPG1	Frizzled-3	clinvar
ABCC1	HGNC:51	ENSG00000103222	P33527	Multidrug resistance-associated protein 1	clinvar
NID1	HGNC:7821	ENSG00000116962	P14543	Nidogen-1	clinvar
PDGFRB	HGNC:8804	ENSG00000113721	P09619	Platelet-derived growth factor receptor beta	clinvar
PLOD1	HGNC:9081	ENSG00000083444	Q02809	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1	clinvar
ACAT2	HGNC:94	ENSG00000120437	Q9BWD1	Acetyl-CoA acetyltransferase, cytosolic	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF4A	Chromosome-associated kinesin KIF4A	Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis.
ARFGEF2	Brefeldin A-inhibited guanine nucleotide-exchange protein 2	Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6.
KCNT1	Potassium channel subfamily T member 1	Sodium-activated K(+) channel.
POMGNT1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins.
CCDC88C	Protein Daple	Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling.
IFT56	Intraflagellar transport protein 56	Component of the intraflagellar transport (IFT) complex B required for transport of proteins in the motile cilium.
BLTP1	Bridge-like lipid transfer protein family member 1	Bridge-like lipid transfer protein that functions as molecular bridges between endoplasmic reticulum and the membranes targeted for lipid delivery.
DNAH9	Dynein axonemal heavy chain 9	Force generating protein required for cilia beating in respiratory epithelia.
DPH1	2-(3-amino-3-carboxypropyl)histidine synthase subunit 1	Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
FZD3	Frizzled-3	Receptor for Wnt proteins.
ABCC1	Multidrug resistance-associated protein 1	Mediates export of organic anions and drugs from the cytoplasm.
NID1	Nidogen-1	Sulfated glycoprotein widely distributed in basement membranes and tightly associated with laminin.
PDGFRB	Platelet-derived growth factor receptor beta	Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, surviv…
PLOD1	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1	Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils.
ACAT2	Acetyl-CoA acetyltransferase, cytosolic	Involved in the biosynthetic pathway of cholesterol.

Protein-family classification

Druggable: 7 · Difficult: 0 · Unknown: 10 · Druggable fraction: 0.41

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
Ion channel	1	6.6×	0.395
Transporter	1	4.6×	0.395
Kinase	2	3.3×	0.395
Enzyme (other)	2	1.4×	0.516
GPCR	1	1.4×	0.516
Other/Unknown	10	1.1×	0.516

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF4A	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
ARFGEF2	Other/Unknown	no		Sec7_dom, ARM-like, Mon2/Sec7/BIG1-like_HDS
KCNT1	Ion channel	yes		RCK_N, K_chnl_BK_asu, K_chnl_dom
POMGNT1	Enzyme (other)	yes	2.4.1.312	Glyco_trans_13, Nucleotide-diphossugar_trans, POMGNT1_PANDER-like
CCDC88C	Other/Unknown	no		CH_dom, CH_dom_sf, HOOK_N
IFT56	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC26
TMEM92	Other/Unknown	no		WBP1-like
BLTP1	Other/Unknown	no		BLTP1, BLTP1_N, BLTP1_M
DNAH9	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DPH1	Other/Unknown	no		DPH1/DPH2, DPH1/DPH2_1, DPH1/DPH2_2
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FZD3	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
ABCC1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP
NID1	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, Thyroglobulin_1
PDGFRB	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
PLOD1	Other/Unknown	no		Procol_lys_dOase, Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph
ACAT2	Enzyme (other)	yes	2.3.1.9	Thiolase, Thiolase-like, Thiolase_AS

Expression context

Cohort genes with no expression data: 0.

17 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)	17
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	3
secondary oocyte	2
ventricular zone	2
right hemisphere of cerebellum	2
C1 segment of cervical spinal cord	2
adenohypophysis	2
apex of heart	2
right uterine tube	2
bronchial epithelial cell	2
epithelium of bronchus	2
Brodmann (1909) area 23	2
corpus callosum	2
oocyte	1
cartilage tissue	1
jejunal mucosa	1
parotid gland	1
cerebellar cortex	1
cerebellar hemisphere	1
granulocyte	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF4A	179	broad	marker	oocyte, secondary oocyte, ventricular zone
ARFGEF2	289	ubiquitous	marker	cartilage tissue, jejunal mucosa, parotid gland
KCNT1	153	tissue_specific	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
POMGNT1	269	ubiquitous	marker	apex of heart, C1 segment of cervical spinal cord, adenohypophysis
CCDC88C	220	ubiquitous	marker	right uterine tube, granulocyte, olfactory segment of nasal mucosa
IFT56	188	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
TMEM92	133	broad	marker	pancreatic ductal cell, ileal mucosa, duodenum
BLTP1	298	ubiquitous	marker	Brodmann (1909) area 23, corpus callosum, postcentral gyrus
DNAH9	184	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
DPH1	140	ubiquitous	marker	pituitary gland, right hemisphere of cerebellum, adenohypophysis
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
FZD3	257	ubiquitous	marker	Brodmann (1909) area 23, secondary oocyte, corpus epididymis
ABCC1	134	ubiquitous	marker	lower esophagus mucosa, lower esophagus, lower esophagus muscularis layer
NID1	262	ubiquitous	marker	stromal cell of endometrium, mucosa of stomach, lower lobe of lung
PDGFRB	270	ubiquitous	marker	stromal cell of endometrium, right coronary artery, endocervix
PLOD1	279	ubiquitous	marker	stromal cell of endometrium, smooth muscle tissue, apex of heart
ACAT2	283	ubiquitous	marker	ventricular zone, ganglionic eminence, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFRB	5,111
ABCC1	3,018
ACAT2	2,250
ARFGEF2	2,022
KIF4A	1,982
PLOD1	1,929
DNAH9	1,841
NID1	1,702
DPH1	1,593
KCNT1	1,562

Structural data

PDB: 10 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR2	P21802	63
POMGNT1	Q8WZA1	10
PDGFRB	P09619	8
KCNT1	Q5JUK3	6
ABCC1	P33527	5
FZD3	Q9NPG1	4
ARFGEF2	Q9Y6D5	2
ACAT2	Q9BWD1	2
KIF4A	O95239	1
DNAH9	Q9NYC9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLOD1	Q02809	93.04
IFT56	A0AVF1	91.82
DPH1	Q9BZG8	87.00
NID1	P14543	78.50
TMEM92	Q6UXU6	67.18
CCDC88C	Q9P219	65.69
BLTP1	Q2LD37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 81. Enrichment computed across 17 evidence-associated genes (13 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 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by FGFR2 amplification mutants	1	878.5×	0.046	FGFR2
Signaling by FGFR2 fusions	1	878.5×	0.046	FGFR2
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	439.2×	0.061	POMGNT1
DAG1 core M1 glycosylations	1	219.6×	0.061	POMGNT1
Negative regulation of TCF-dependent signaling by DVL-interacting proteins	1	175.7×	0.061	CCDC88C
DAG1 core M2 glycosylations	1	175.7×	0.061	POMGNT1
Metabolism of porphyrins	1	109.8×	0.061	ABCC1
Synthesis of diphthamide-EEF2	1	109.8×	0.061	DPH1
Transport of RCbl within the body	1	109.8×	0.061	ABCC1
NFE2L2 regulating MDR associated enzymes	1	109.8×	0.061	ABCC1
Constitutive Signaling by Aberrant PI3K in Cancer	2	19.5×	0.061	FGFR2, PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	14.9×	0.061	FGFR2, PDGFRB
FGFR2b ligand binding and activation	1	87.8×	0.066	FGFR2
Cholesterol biosynthesis	1	87.8×	0.066	ACAT2
FGFR2c ligand binding and activation	1	67.6×	0.070	FGFR2
Heme degradation	1	62.8×	0.070	ABCC1
Matriglycan biosynthesis on DAG1	1	62.8×	0.070	POMGNT1
Lanosterol biosynthesis	1	58.6×	0.070	ACAT2
Activated point mutants of FGFR2	1	51.7×	0.070	FGFR2
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	48.8×	0.070	ABCC1
Phospholipase C-mediated cascade; FGFR2	1	48.8×	0.070	FGFR2
Signaling by FGFR2 IIIa TM	1	46.2×	0.070	FGFR2
Synthesis of Leukotrienes (LT) and Eoxins (EX)	1	43.9×	0.070	ABCC1
Arachidonate metabolism	1	43.9×	0.070	ABCC1
PIP3 activates AKT signaling	2	10.3×	0.070	FGFR2, PDGFRB
RAF/MAP kinase cascade	2	9.4×	0.070	FGFR2, PDGFRB
PI-3K cascade:FGFR2	1	38.2×	0.078	FGFR2
SHC-mediated cascade:FGFR2	1	36.6×	0.078	FGFR2
FRS-mediated FGFR2 signaling	1	33.8×	0.079	FGFR2
FGFR2 alternative splicing	1	32.5×	0.079	FGFR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 16 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	1053.2×	0.017	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	1053.2×	0.017	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	1053.2×	0.017	FGFR2
antigen processing and presentation of lipid antigen via MHC class Ib	1	1053.2×	0.017	ABCC1
lateral sprouting from an epithelium	1	1053.2×	0.017	FGFR2
cell migration involved in coronary angiogenesis	1	1053.2×	0.017	PDGFRB
cyclic nucleotide transport	1	1053.2×	0.017	ABCC1
metanephric glomerular mesangial cell proliferation involved in metanephros development	1	1053.2×	0.017	PDGFRB
sphingolipid translocation	1	1053.2×	0.017	ABCC1
intracellular nitrogen homeostasis	1	1053.2×	0.017	ABCC1
mucociliary clearance	2	162.0×	0.017	CCDC88C, DNAH9
non-canonical Wnt signaling pathway	2	72.6×	0.017	CCDC88C, FZD3
basement membrane organization	2	63.8×	0.017	POMGNT1, NID1
Wnt signaling pathway, planar cell polarity pathway	2	56.9×	0.017	CCDC88C, FZD3
peptidyl-tyrosine phosphorylation	2	52.7×	0.017	FGFR2, PDGFRB
endomembrane system organization	1	526.6×	0.019	ARFGEF2
orbitofrontal cortex development	1	526.6×	0.019	FGFR2
cell migration involved in vasculogenesis	1	526.6×	0.019	PDGFRB
pigment accumulation	1	526.6×	0.019	ABCC1
negative regulation of mitotic cell cycle, embryonic	1	526.6×	0.019	FZD3
prostate gland morphogenesis	1	526.6×	0.019	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	526.6×	0.019	FGFR2
mammary gland bud formation	1	526.6×	0.019	FGFR2
branch elongation involved in salivary gland morphogenesis	1	526.6×	0.019	FGFR2
mesenchymal cell differentiation involved in lung development	1	526.6×	0.019	FGFR2
smooth muscle cell chemotaxis	1	526.6×	0.019	PDGFRB
respiratory basal cell differentiation	1	526.6×	0.019	CCDC88C
inner ear morphogenesis	2	37.6×	0.019	FGFR2, FZD3
granuloma formation	1	351.1×	0.019	ABCC1
farnesyl diphosphate biosynthetic process, mevalonate pathway	1	351.1×	0.019	ACAT2

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 13

Druggability breadth: 9 of 17 evidence-associated genes (53%) 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
KCNT1	BEPRIDIL
FGFR2	PONATINIB
ABCC1	RIMONABANT
PDGFRB	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRB	102	4
FGFR2	59	4
ABCC1	23	4
KCNT1	2	4
KIF4A	0	0
ARFGEF2	0	0
POMGNT1	0	0
CCDC88C	0	0
IFT56	0	0
TMEM92	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1
PONATINIB	4	FGFR2, PDGFRB
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2, PDGFRB
FEDRATINIB	4	FGFR2, PDGFRB
LENVATINIB	4	FGFR2, PDGFRB
AXITINIB	4	FGFR2, PDGFRB
SORAFENIB	4	FGFR2, PDGFRB
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2, PDGFRB
NINTEDANIB ESYLATE	4	FGFR2, PDGFRB
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2, PDGFRB
SUNITINIB	4	FGFR2, PDGFRB
DASATINIB	4	FGFR2, PDGFRB
ERLOTINIB	4	FGFR2, PDGFRB
MIDOSTAURIN	4	FGFR2, PDGFRB
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
PDGFRB	1,237	Binding:1213, Functional:16, ADMET:8
FGFR2	966	Binding:940, Functional:22, ADMET:4
ABCC1	459	Binding:270, Functional:166, ADMET:23
KCNT1	24	Binding:24
KIF4A	20	Binding:20
ACAT2	3	Binding:3
ARFGEF2	1	Binding:1
POMGNT1	1	Binding:1
PLOD1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POMGNT1	2.4.1.312	protein O-mannose beta-1,4-N-acetylglucosaminyltransferase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
ABCC1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
PDGFRB	2.7.10.1	receptor protein-tyrosine kinase
ACAT2	2.3.1.9	acetyl-CoA C-acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FGFR2	966
ABCC1	459
PDGFRB	1,237

Pharmacogenomics

Cohort genes with a PharmGKB record: 17; 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)
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1
PONATINIB	4	FGFR2, PDGFRB
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2, PDGFRB
FEDRATINIB	4	FGFR2, PDGFRB
LENVATINIB	4	FGFR2, PDGFRB
AXITINIB	4	FGFR2, PDGFRB
SORAFENIB	4	FGFR2, PDGFRB
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2, PDGFRB
NINTEDANIB ESYLATE	4	FGFR2, PDGFRB
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2, PDGFRB
SUNITINIB	4	FGFR2, PDGFRB
DASATINIB	4	FGFR2, PDGFRB
ERLOTINIB	4	FGFR2, PDGFRB
MIDOSTAURIN	4	FGFR2, PDGFRB
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	KCNT1, FGFR2, ABCC1, PDGFRB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	POMGNT1, FZD3, ACAT2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	10	KIF4A, ARFGEF2, CCDC88C, IFT56, TMEM92, BLTP1, DNAH9, DPH1, NID1, PLOD1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KIF4A	20	—
ARFGEF2	1	—
POMGNT1	1	—
CCDC88C	0	—
IFT56	0	—
TMEM92	0	—
BLTP1	0	—
DNAH9	0	—
DPH1	0	—
FZD3	0	—
NID1	0	—
PLOD1	1	—
ACAT2	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 125.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	111
PHASE3	6
PHASE4	4
PHASE1/PHASE2	2
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07547826	PHASE4	NOT_YET_RECRUITING	Efficacy and Cost-Effectiveness of Topical Vancomycin Powder in Preventing Pediatric Ventriculoperitoneal Shunt Infections Across Different Etiologies
NCT01323764	PHASE4	COMPLETED	ShuntCheck Versus Radionuclide in Evaluating Shunt Function in Symptomatic NPH Patients
NCT01685450	PHASE4	UNKNOWN	NIMIP: Non Invasive Measurement of the Intracranial Pressure
NCT03513757	PHASE4	COMPLETED	Dexmedetomidine and Propofol for Pediatric MRI Sedation
NCT01936272	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Shunt vs ETV/CPC for PIH in Ugandan Infants
NCT04177914	PHASE3	RECRUITING	HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants
NCT00196196	PHASE3	COMPLETED	A Precision and Accuracy Study of the Codman Valve Position Verification (VPV) System.
NCT00286104	PHASE3	COMPLETED	Impact of Ventricular Catheter Used With Antimicrobial Agents on Patients With a Ventricular Catheter
NCT02425761	PHASE3	UNKNOWN	The CSF Shunt Entry Site Trial
NCT02512809	PHASE3	TERMINATED	Isoflurane-induced Neuroinflammation in Children With Hydrocephalus
NCT00652470	PHASE2	COMPLETED	A Study Comparing Two Treatments for Infants With Hydrocephalus
NCT01878136	PHASE1/PHASE2	WITHDRAWN	Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage
NCT05476874	PHASE1/PHASE2	UNKNOWN	Improvement of Peritoneal Catheter Placement in VPS With a Splitable Trocar
NCT05001750	PHASE1	RECRUITING	Prophylactic Antibiotics Useful With Antibiotic Impregnated External Ventricular Drains (EVDs)?
NCT02230124	Not specified	ACTIVE_NOT_RECRUITING	Magnetic Resonance Elastography in Hydrocephalus
NCT02601339	Not specified	RECRUITING	NIRS Monitoring in Premature Infants
NCT03327467	Not specified	AVAILABLE	Expanded Access Protocol: Umbilical Cord Blood Infusions for Children With Brain Injuries
NCT03650101	Not specified	ACTIVE_NOT_RECRUITING	Improving Infant Hydrocephalus Outcomes in Uganda
NCT04099823	Not specified	RECRUITING	MR Evaluation of Cerebrospinal Fluid (CSF) Dynamics
NCT04189172	Not specified	ACTIVE_NOT_RECRUITING	MiDura-Study (Neuro-Patch in Duraplasty)
NCT04436068	Not specified	ACTIVE_NOT_RECRUITING	Hyperfine Portable MRI in Hydrocephalus and Other Conditions Prompting Outpatient Brain Imaging
NCT04746625	Not specified	RECRUITING	Safety and Performance of the Polaris® 24 Adjustable Valve System in Hydrocephalus Patients’ Treatment
NCT04758611	Not specified	ACTIVE_NOT_RECRUITING	The ETCHES I Study (Endovascular Treatment of Communicating Hydrocephalus With an Endovascular Shunt)
NCT05232838	Not specified	ACTIVE_NOT_RECRUITING	US Pilot Study of the CereVasc® eShunt® System in Normal Pressure Hydrocephalus
NCT05250505	Not specified	ACTIVE_NOT_RECRUITING	Pilot Study of the CereVasc® eShunt® System in Normal Pressure Hydrocephalus
NCT05397106	Not specified	ACTIVE_NOT_RECRUITING	Post Market Clinical Follow-up of CODMAN CERTAS Programmable Valve
NCT05546996	Not specified	RECRUITING	EVD Drainage Data and Intracranial Pressure (ICP) Measurements
NCT05910944	Not specified	RECRUITING	European Study of Prodromal iNPH
NCT06040697	Not specified	RECRUITING	Formative Usability Assessment of Wireless Thermal Anisotropy Devices
NCT06086561	Not specified	RECRUITING	Longitudinal Measurements of Flow in Cerebrospinal Fluid Shunts With a Wireless Thermal Anisotropy Measurement Device
NCT06253858	Not specified	RECRUITING	Ultrasound (US) Guided External Ventricular Catheter Placement
NCT06276543	Not specified	RECRUITING	Bactiseal Catheter Safety Registry Study
NCT06368648	Not specified	RECRUITING	CoMind Early Feasibility Study
NCT06402786	Not specified	ACTIVE_NOT_RECRUITING	First-in-human Trial of Home Brain Pressure Measured Using Kitea ICP Sensor, Placed During Hydrocephalus Shunt Surgery.
NCT06409286	Not specified	NOT_YET_RECRUITING	Assessment of Flow in Cerebrospinal Fluid Shunts With a Second Generation Wireless Thermal Anisotropy Measurement Device
NCT06410885	Not specified	NOT_YET_RECRUITING	Assessment of Flow in Cerebrospinal Fluid Shunts With a Wireless Thermal Anisotropy Measurement Device in Asymptomatic Patients
NCT06419842	Not specified	RECRUITING	Impact of Hypnosis for Performing Lumbar Infusion Tests
NCT06428734	Not specified	RECRUITING	Clinical Outcome in Patients With INPH
NCT06486909	Not specified	RECRUITING	Shunt-dependency After aSAH - Role of Early Hyperglycaemia in CSF and Blood
NCT06703164	Not specified	NOT_YET_RECRUITING	Late Post Traumatic Ventriculomegally Does it Requires CSF Diversion ?

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GLYCOPYRRONIUM	4	3
ENTECAVIR	4	1
ISOFLURANE	4	1
NITROUS OXIDE	4	1
SEVOFLURANE	4	1
UROKINASE	4	1
VANCOMYCIN	4	1
CHEMBL4299436	0	1