Isolated oxycephaly

Summary

Isolated oxycephaly (MONDO:0018971) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated oxycephaly
Mondo ID	MONDO:0018971
Orphanet	63440
SNOMED CT	48069004
UMLS	C5399823
MedGen	1726910
GARD	0025134
Is cancer (heuristic)	no

Also known as: acrocephaly · hypsicephaly · hypsocephaly · pyrgocephaly · turricephaly

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › dysostosis › synostosis › craniosynostosis › isolated craniosynostosis › isolated oxycephaly

Related subtypes (3): isolated cloverleaf skull syndrome, isolated trigonocephaly, non-syndromic unisutural craniosynostosis

Subtypes (2): TWIST1-related craniosynostosis, craniosynostosis 6

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
562131	GRCh37/hg19 9p23-22.2(chr9:13563537-18491752)x1	CCDC171	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 3 · 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
ZIC1	Supportive	Autosomal dominant	isolated plagiocephaly	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZIC1	Orphanet:269212	Isolated Dandy-Walker malformation with hydrocephalus
ZIC1	Orphanet:269215	Isolated Dandy-Walker malformation without hydrocephalus
ZIC1	Orphanet:35099	Non-syndromic bicoronal craniosynostosis

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
ZIC1	HGNC:12872	ENSG00000152977	Q15915	Zinc finger protein ZIC 1	gencc
CCDC171	HGNC:29828	ENSG00000164989	Q6TFL3	Coiled-coil domain-containing protein 171	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZIC1	Zinc finger protein ZIC 1	Acts as a transcriptional activator.

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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZIC1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Znf_ZIC
CCDC171	Other/Unknown	no		CCDC171

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
cerebellum	1
cranial nerve II	1
paraflocculus	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZIC1	196	broad	marker	paraflocculus, cranial nerve II, cerebellum
CCDC171	181	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZIC1	2,710
CCDC171	586

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCDC171	Q6TFL3	71.56
ZIC1	Q15915	55.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Specification of the neural plate border	1	634.4×	0.003	ZIC1
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.006	ZIC1

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
maintenance of cell number	1	8426.0×	0.002	ZIC1
olfactory bulb development	1	766.0×	0.005	ZIC1
regulation of smoothened signaling pathway	1	624.1×	0.005	ZIC1
spinal cord development	1	510.7×	0.005	ZIC1
adult walking behavior	1	495.6×	0.005	ZIC1
pattern specification process	1	468.1×	0.005	ZIC1
positive regulation of protein import into nucleus	1	421.3×	0.005	ZIC1
inner ear morphogenesis	1	300.9×	0.006	ZIC1
hippocampus development	1	230.8×	0.007	ZIC1
central nervous system development	1	115.4×	0.013	ZIC1
gene expression	1	79.9×	0.016	ZIC1
brain development	1	79.5×	0.016	ZIC1
cell differentiation	1	29.1×	0.038	ZIC1
positive regulation of DNA-templated transcription	1	27.9×	0.038	ZIC1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ZIC1

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
ZIC1	0	0
CCDC171	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	ZIC1, CCDC171

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)
ZIC1	0	—
CCDC171	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.