Occipital encephalocele

Summary

Occipital encephalocele (MONDO:0017080) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	occipital encephalocele
Mondo ID	MONDO:0017080
Orphanet	268823
ICD-10-CM	Q01.2
ICD-11	1075031814
SNOMED CT	42376006
UMLS	C0014067
MedGen	4935
GARD	0020969
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › cephalocele › isolated encephalocele › occipital encephalocele

Related subtypes (4): nasal encephalocele, frontal encephalocele, parietal encephalocele, basal encephalocele

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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
217626	NM_025114.4(CEP290):c.4393C>T (p.Arg1465Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
217635	NM_025114.4(CEP290):c.4882C>T (p.Gln1628Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
523535	NM_025114.4(CEP290):c.5710-3C>G	CEP290	Likely pathogenic	criteria provided, single submitter
428608	NC_000001.10:g.85569702_85585573del	DNAI3	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis

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
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
DNAI3	HGNC:30711	ENSG00000162643	Q8IWG1	Dynein axonemal intermediate chain 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
DNAI3	Dynein axonemal intermediate chain 3	Acts as a negative regulator of cell migration, invasion, and metastasis downstream of p53/TP53, through inhibition of Arp2/3 complex-mediated actin polymerization.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
DNAI3	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf

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
right uterine tube	2
male germ line stem cell (sensu Vertebrata) in testis	1
ventricular zone	1
bronchial epithelial cell	1
bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
DNAI3	160	broad	marker	bronchial epithelial cell, bronchus, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP290	2,778
DNAI3	801

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNAI3	Q8IWG1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 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
Centrosome maturation	1	253.8×	0.016	CEP290
Loss of Nlp from mitotic centrosomes	1	158.6×	0.016	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.016	CEP290
AURKA Activation by TPX2	1	152.3×	0.016	CEP290
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.016	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.016	CEP290
Mitotic G2-G2/M phases	1	126.9×	0.016	CEP290
G2/M Transition	1	126.9×	0.016	CEP290
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.016	CEP290
Anchoring of the basal body to the plasma membrane	1	113.1×	0.016	CEP290
Cilium Assembly	1	108.8×	0.016	CEP290
Mitotic Prometaphase	1	69.2×	0.021	CEP290
Organelle biogenesis and maintenance	1	66.0×	0.021	CEP290
M Phase	1	66.0×	0.021	CEP290
Cell Cycle, Mitotic	1	48.2×	0.026	CEP290
Cell Cycle	1	36.0×	0.033	CEP290
Innate Immune System	1	25.5×	0.044	CEP290
Neutrophil degranulation	1	23.1×	0.046	CEP290
Immune System	1	13.0×	0.077	CEP290

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
obsolete ciliary basal body-plasma membrane docking	1	4213.0×	0.003	CEP290
ciliary transition zone assembly	1	2808.7×	0.003	CEP290
negative regulation of Arp2/3 complex-mediated actin nucleation	1	1203.7×	0.003	DNAI3
pronephros development	1	1203.7×	0.003	CEP290
regulation of establishment of protein localization	1	1203.7×	0.003	CEP290
otic vesicle formation	1	1053.2×	0.003	CEP290
hindbrain development	1	561.7×	0.005	CEP290
inner dynein arm assembly	1	443.5×	0.005	DNAI3
eye photoreceptor cell development	1	421.3×	0.005	CEP290
cilium movement involved in cell motility	1	337.0×	0.005	DNAI3
positive regulation of intracellular protein transport	1	337.0×	0.005	CEP290
camera-type eye development	1	179.3×	0.009	CEP290
non-motile cilium assembly	1	145.3×	0.010	CEP290
positive regulation of osteoblast differentiation	1	112.3×	0.012	DNAI3
kidney development	1	70.2×	0.018	CEP290
negative regulation of cell migration	1	55.8×	0.021	DNAI3
cilium assembly	1	36.8×	0.030	CEP290
protein transport	1	21.9×	0.048	CEP290
positive regulation of DNA-templated transcription	1	14.0×	0.070	CEP290

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CEP290	0	0
DNAI3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CEP290, DNAI3

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)
CEP290	0	—
DNAI3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.