Microcephaly 6 with or without short stature

Summary

Microcephaly 6 with or without short stature (MONDO:0700054) is a disease caused by CPAP (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CPAP (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 6 with or without short stature
Mondo ID	MONDO:0700054
GARD	0026336
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive primary microcephaly › microcephaly with or without short stature › microcephaly 6 with or without short stature

Subtypes (2): microcephaly 6, primary, autosomal recessive, Seckel syndrome 4

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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3779046	NC_000016.10:g.25468219_25468220del		Likely pathogenic	criteria provided, single submitter
3779047	NC_000016.10:g.25472686_25472692del		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
CPAP	Definitive	Autosomal recessive	microcephaly 6 with or without short stature	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPAP	Orphanet:2512	Autosomal recessive primary microcephaly
CPAP	Orphanet:808	Seckel syndrome

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
CPAP	HGNC:17272	ENSG00000151849	Q9HC77	Centrosomal P4.1-associated protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPAP	Centrosomal P4.1-associated protein	Plays an important role in cell division and centrosome function by participating in centriole duplication.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPAP	Other/Unknown	no		CENPJ_C_dom, TCP10L/CENPJ, Tcp10_C_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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPAP	246	ubiquitous	marker	sperm, left lobe of thyroid gland, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CPAP	2,242

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CPAP	Q9HC77	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1	519.1×	0.009	CPAP
Loss of Nlp from mitotic centrosomes	1	158.6×	0.009	CPAP
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.009	CPAP
AURKA Activation by TPX2	1	152.3×	0.009	CPAP
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.009	CPAP
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.009	CPAP
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.009	CPAP
Anchoring of the basal body to the plasma membrane	1	113.1×	0.009	CPAP

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
astral microtubule nucleation	1	16852.0×	0.001	CPAP
centriole elongation	1	4213.0×	0.001	CPAP
positive regulation of centriole replication	1	3370.4×	0.001	CPAP
positive regulation of establishment of protein localization	1	2808.7×	0.001	CPAP
positive regulation of centriole elongation	1	2407.4×	0.001	CPAP
positive regulation of spindle assembly	1	2106.5×	0.001	CPAP
positive regulation of non-motile cilium assembly	1	1872.4×	0.001	CPAP
regulation of centriole replication	1	1685.2×	0.001	CPAP
microtubule polymerization	1	887.0×	0.002	CPAP
regulation of mitotic spindle organization	1	842.6×	0.002	CPAP
centriole replication	1	732.7×	0.002	CPAP
microtubule nucleation	1	624.1×	0.003	CPAP
motile cilium assembly	1	581.1×	0.003	CPAP
positive regulation of receptor signaling pathway via JAK-STAT	1	432.1×	0.003	CPAP
positive regulation of G1/S transition of mitotic cell cycle	1	401.2×	0.003	CPAP
non-motile cilium assembly	1	290.6×	0.004	CPAP
smoothened signaling pathway	1	181.2×	0.006	CPAP
cilium assembly	1	73.6×	0.014	CPAP
cell division	1	46.2×	0.022	CPAP

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
CPAP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CPAP

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)
CPAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.