Seckel syndrome 5

Summary

Seckel syndrome 5 (MONDO:0013443) is a disease caused by CEP152 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CEP152 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 138

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Seckel syndrome 5
Mondo ID	MONDO:0013443
OMIM	613823
DOID	DOID:0070012
UMLS	C3151187
MedGen	462537
GARD	0015719
Is cancer (heuristic)	no

Also known as: CEP152 Seckel syndrome · SCKL5 · Seckel syndrome 5 · Seckel syndrome caused by mutation in CEP152 · Seckel syndrome type 5

Data availability: 138 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Seckel syndrome › Seckel syndrome 5

Related subtypes (11): Seckel syndrome 1, intrauterine growth retardation with increased mitomycin c sensitivity, Seckel syndrome 2, Seckel syndrome 4, Seckel syndrome 6, Seckel syndrome 7, Seckel syndrome 8, microcephaly 13, primary, autosomal recessive, Seckel syndrome 9, Seckel syndrome 10, Seckel syndrome 11

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

138 retrieved; paginated sample, class counts are floors:

45 uncertain significance, 42 conflicting classifications of pathogenicity, 14 benign, 12 pathogenic/likely pathogenic, 12 benign/likely benign, 8 likely pathogenic, 4 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069366	NM_001194998.2(CEP152):c.2318G>A (p.Trp773Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1186425	NM_001194998.2(CEP152):c.467dup (p.Gln157fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158240	NM_001194998.2(CEP152):c.2034T>G (p.Tyr678Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158250	NM_001194998.2(CEP152):c.3016del (p.Thr1006fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1676669	NM_001194998.2(CEP152):c.2034_2036del (p.Tyr678_Gln679delinsTer)	CEP152	Pathogenic	criteria provided, multiple submitters, no conflicts
2189940	NM_001194998.2(CEP152):c.799C>T (p.Arg267Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2636246	NM_001194998.2(CEP152):c.3172del (p.Gln1058fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2715024	NM_001194998.2(CEP152):c.903_904del (p.Glu301fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2784802	NM_001194998.2(CEP152):c.3829del (p.Ile1277fs)	CEP152	Pathogenic	criteria provided, single submitter
2844652	NM_001194998.2(CEP152):c.3925C>T (p.Arg1309Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2857443	NM_001194998.2(CEP152):c.527G>A (p.Trp176Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3021593	NM_001194998.2(CEP152):c.1613C>G (p.Ser538Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31030	NM_001194998.2(CEP152):c.261+1G>C	CEP152	Pathogenic	no assertion criteria provided
55	NM_001194998.2(CEP152):c.794A>C (p.Gln265Pro)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
931704	NM_001194998.2(CEP152):c.343C>T (p.Arg115Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
403711	NM_018451.5(CPAP):c.3936_3939del (p.His1313fs)	CPAP	Pathogenic	no assertion criteria provided
1324053	NM_001194998.2(CEP152):c.972+2T>A	CEP152	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505978	NM_001194998.2(CEP152):c.1908+1G>T	CEP152	Likely pathogenic	criteria provided, multiple submitters, no conflicts
31032	NM_001194998.2(CEP152):c.2694+1G>T	CEP152	Likely pathogenic	criteria provided, single submitter
3577345	NM_001194998.2(CEP152):c.3954C>A (p.Cys1318Ter)	CEP152	Likely pathogenic	criteria provided, single submitter
3577346	NM_001194998.2(CEP152):c.1981C>T (p.Gln661Ter)	CEP152	Likely pathogenic	criteria provided, single submitter
3577347	NM_001194998.2(CEP152):c.1768del (p.Ser590fs)	CEP152	Likely pathogenic	criteria provided, single submitter
3577349	NM_001194998.2(CEP152):c.880_883del (p.Phe294fs)	CEP152	Likely pathogenic	criteria provided, single submitter
930905	NM_001194998.2(CEP152):c.528G>A (p.Trp176Ter)	CEP152	Likely pathogenic	criteria provided, single submitter
1327252	NM_001194998.2(CEP152):c.4330C>T (p.Gln1444Ter)	CEP152	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1374147	NM_001194998.2(CEP152):c.863G>A (p.Arg288Gln)	CEP152	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158224	NM_001194998.2(CEP152):c.1180A>G (p.Ile394Val)	CEP152	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158230	NM_001194998.2(CEP152):c.1578-6C>G	CEP152	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158234	NM_001194998.2(CEP152):c.1866G>T (p.Leu622=)	CEP152	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158242	NM_001194998.2(CEP152):c.2262G>A (p.Glu754=)	CEP152	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CEP152	Definitive	Autosomal recessive	Seckel syndrome 5	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP152	Orphanet:2512	Autosomal recessive primary microcephaly
CEP152	Orphanet:808	Seckel syndrome
CPAP	Orphanet:2512	Autosomal recessive primary microcephaly
CPAP	Orphanet:808	Seckel syndrome

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
CEP152	HGNC:29298	ENSG00000103995	O94986	Centrosomal protein of 152 kDa	gencc,clinvar
CPAP	HGNC:17272	ENSG00000151849	Q9HC77	Centrosomal P4.1-associated protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP152	Centrosomal protein of 152 kDa	Necessary for centrosome duplication; the function also seems to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication.
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: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP152	Other/Unknown	no		CEP152/SHC-Transforming, CEP152_CC, CEP152_PLK4_bind
CPAP	Other/Unknown	no		CENPJ_C_dom, TCP10L/CENPJ, Tcp10_C_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
sperm	2
oocyte	1
secondary oocyte	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP152	218	ubiquitous	marker	secondary oocyte, oocyte, sperm
CPAP	246	ubiquitous	marker	sperm, left lobe of thyroid gland, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CPAP	2,242
CEP152	1,205

Intra-cohort edges

A	B	Sources
CEP152	CPAP	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CPAP	Q9HC77	6
CEP152	O94986	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of Nlp from mitotic centrosomes	2	158.6×	2e-04	CEP152, CPAP
Loss of proteins required for interphase microtubule organization from the centrosome	2	158.6×	2e-04	CEP152, CPAP
AURKA Activation by TPX2	2	152.3×	2e-04	CEP152, CPAP
Recruitment of mitotic centrosome proteins and complexes	2	135.9×	2e-04	CEP152, CPAP
Regulation of PLK1 Activity at G2/M Transition	2	126.9×	2e-04	CEP152, CPAP
Recruitment of NuMA to mitotic centrosomes	2	116.5×	2e-04	CEP152, CPAP
Anchoring of the basal body to the plasma membrane	2	113.1×	2e-04	CEP152, CPAP
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1	259.6×	0.008	CPAP
Centrosome maturation	1	126.9×	0.015	CEP152
Mitotic G2-G2/M phases	1	63.4×	0.024	CEP152
G2/M Transition	1	63.4×	0.024	CEP152
Cilium Assembly	1	54.4×	0.026	CEP152
Mitotic Prometaphase	1	34.6×	0.034	CEP152
Organelle biogenesis and maintenance	1	33.0×	0.034	CEP152
M Phase	1	33.0×	0.034	CEP152
Cell Cycle, Mitotic	1	24.1×	0.044	CEP152
Cell Cycle	1	18.0×	0.055	CEP152

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
centriole replication	2	732.7×	4e-05	CEP152, CPAP
astral microtubule nucleation	1	8426.0×	0.001	CPAP
centriole elongation	1	2106.5×	0.003	CPAP
positive regulation of centriole replication	1	1685.2×	0.003	CPAP
de novo centriole assembly involved in multi-ciliated epithelial cell differentiation	1	1685.2×	0.003	CEP152
positive regulation of establishment of protein localization	1	1404.3×	0.003	CPAP
positive regulation of centriole elongation	1	1203.7×	0.003	CPAP
positive regulation of spindle assembly	1	1053.2×	0.003	CPAP
positive regulation of non-motile cilium assembly	1	936.2×	0.003	CPAP
regulation of centriole replication	1	842.6×	0.003	CPAP
centrosome duplication	1	468.1×	0.004	CEP152
microtubule polymerization	1	443.5×	0.004	CPAP
regulation of mitotic spindle organization	1	421.3×	0.004	CPAP
microtubule nucleation	1	312.1×	0.005	CPAP
motile cilium assembly	1	290.6×	0.005	CPAP
positive regulation of receptor signaling pathway via JAK-STAT	1	216.1×	0.006	CPAP
positive regulation of G1/S transition of mitotic cell cycle	1	200.6×	0.006	CPAP
cell projection organization	1	187.2×	0.007	CEP152
non-motile cilium assembly	1	145.3×	0.008	CPAP
smoothened signaling pathway	1	90.6×	0.012	CPAP
cilium assembly	1	36.8×	0.028	CPAP
cell division	1	23.1×	0.043	CPAP

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
CEP152	0	0
CPAP	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	CEP152, CPAP

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)
CEP152	0	—
CPAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.