CEP152

Summary

CEP152 (centrosomal protein 152, HGNC:29298) is a protein-coding gene on chromosome 15q21.1, encoding Centrosomal protein of 152 kDa (O94986). 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. It is a selective cancer dependency (DepMap: 16.7% of cell lines).

This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 22995 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly with or without short stature (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,268 total — 96 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 70
• Cancer dependency (DepMap): dependent in 16.7% of screened cell lines
• MANE Select transcript: NM_001194998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29298
Approved symbol	CEP152
Name	centrosomal protein 152
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0912, SCKL5, MCPH9
Ensembl gene	ENSG00000103995
Ensembl biotype	protein_coding
OMIM	613529
Entrez	22995

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 non_stop_decay, 1 nonsense_mediated_decay

ENST00000325747, ENST00000380950, ENST00000399334, ENST00000558337, ENST00000558591, ENST00000559398, ENST00000559444, ENST00000559630, ENST00000560322, ENST00000561245

RefSeq mRNA: 2 — MANE Select: NM_001194998 NM_001194998, NM_014985

CCDS: CCDS42033, CCDS58361

Canonical transcript exons

ENST00000380950 — 27 exons

Exon	Start	End
ENSE00000931316	48760135	48760266
ENSE00000931317	48762391	48762672
ENSE00000931318	48767060	48767192
ENSE00000931319	48767335	48767463
ENSE00000931320	48768219	48768328
ENSE00000931321	48768956	48769081
ENSE00000931323	48781196	48781359
ENSE00000931324	48782139	48782230
ENSE00000931325	48783973	48784120
ENSE00000931327	48791237	48791376
ENSE00000931328	48793321	48793461
ENSE00000931329	48796010	48796160
ENSE00000931330	48797661	48797730
ENSE00000931331	48797948	48798051
ENSE00000942133	48755903	48756553
ENSE00000942134	48752349	48752469
ENSE00000942135	48748443	48748610
ENSE00000942136	48744896	48744992
ENSE00000942137	48744240	48744343
ENSE00000942138	48741947	48742100
ENSE00001486949	48797301	48797579
ENSE00001650594	48737938	48739288
ENSE00002541179	48741601	48741704
ENSE00002553855	48810961	48811069
ENSE00003549989	48788801	48789001
ENSE00003578483	48805563	48805656
ENSE00003662003	48772487	48772691

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 92.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9032 / max 294.4386, expressed in 1536 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149790	6.7012	1503
149789	2.1885	734
149788	0.0135	3

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.41	gold quality
oocyte	CL:0000023	92.22	gold quality
sperm	CL:0000019	91.59	gold quality
sural nerve	UBERON:0015488	91.30	gold quality
male germ cell	CL:0000015	88.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.35	gold quality
buccal mucosa cell	CL:0002336	86.20	gold quality
calcaneal tendon	UBERON:0003701	85.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.97	gold quality
ventricular zone	UBERON:0003053	82.29	gold quality
bone marrow	UBERON:0002371	81.57	gold quality
trabecular bone tissue	UBERON:0002483	81.12	gold quality
right testis	UBERON:0004534	79.98	gold quality
left testis	UBERON:0004533	79.69	gold quality
testis	UBERON:0000473	79.28	gold quality
bone marrow cell	CL:0002092	78.36	gold quality
colonic epithelium	UBERON:0000397	77.63	gold quality
monocyte	CL:0000576	77.17	gold quality
mononuclear cell	CL:0000842	77.03	gold quality
leukocyte	CL:0000738	76.64	gold quality
ganglionic eminence	UBERON:0004023	76.60	gold quality
placenta	UBERON:0001987	75.93	gold quality
stromal cell of endometrium	CL:0002255	75.63	gold quality
tonsil	UBERON:0002372	74.01	gold quality
jejunal mucosa	UBERON:0000399	73.62	gold quality
tibial nerve	UBERON:0001323	73.38	gold quality
adrenal tissue	UBERON:0018303	73.04	gold quality
rectum	UBERON:0001052	72.58	gold quality
lower esophagus mucosa	UBERON:0035834	72.58	gold quality
granulocyte	CL:0000094	72.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting CEP152, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-937-5P	97.43	68.39	667
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• CEP152 is a strong candidate for the causal gene underlying MCPH4 and may be an important gene in the evolution of human brain size. (PMID:20598275)
• Drosophila Asl and human CEP152 are required for the centrosomal loading of Plk4 in Drosophila and CPAP in human cells, respectively (PMID:20852615)
• Results suggest that Cep152 recruits Plk4 and CPAP to the centrosome to ensure a faithful centrosome duplication process. (PMID:21059844)
• Data show that Cep152 can be phosphorylated by Plk4 in vitro, suggesting that Cep152 acts with Plk4 to initiate centriole formation. (PMID:21059850)
• CEP152 is a genome maintenance protein disrupted in Seckel syndrome (PMID:21131973)
• Cep57, Cep63, and Cep152 are parts of a ring-like complex localizing around the proximal end of centrioles. (PMID:23333316)
• cooperation between Cep192 and Cep152 is crucial for centriole recruitment of Plk4 and centriole duplication during the cell cycle. (PMID:23641073)
• both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. (PMID:23936128)
• Found that both sc-54 and ab18 antibodies recognize not only Cdk1 but also Cep152 in Western blot and immunofluorescence assays. (PMID:24137814)
• Loss of the Cep192- or Cep152-dependent interaction with Plk4 resulted in impaired centriole duplication that led to delayed cell proliferation. (PMID:24277814)
• Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer. (PMID:24997597)
• results demonstrate the different roles of Cep192 and Cep152 in MTOC remodeling and a novel regulatory mechanism during meiotic spindle formation in mouse oocytes. (PMID:28970258)
• Study shows that Cep63 and Cep152 cooperatively generate a heterotetrameric alpha-helical bundle that functions in conjunction with its neighboring hydrophobic motifs to self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk4, a key regulator for centriole duplication. Mutations disrupting the self-assembly abrogate Plk4-mediated centriole duplication. (PMID:30858376)
• Requirement of the Cep57-Cep63 Interaction for Proper Cep152 Recruitment and Centriole Duplication. (PMID:32152252)
• Polymorphism in miRNA target sites of CEP-63 and CEP-152 ring complex influences expression of CEP genes and favors tumorigenesis in glioma. (PMID:34156311)
• Centrosomal organization of Cep152 provides flexibility in Plk4 and procentriole positioning. (PMID:37707473)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep152	ENSDARG00000075725
mus_musculus	Cep152	ENSMUSG00000068394
rattus_norvegicus	Cep152	ENSRNOG00000065817

Paralogs (3): SHC3 (ENSG00000148082), SHC1 (ENSG00000160691), SHC4 (ENSG00000185634)

Protein

Protein identifiers

Centrosomal protein of 152 kDa — O94986 (reviewed: O94986)

All UniProt accessions (4): A0A075B719, O94986, H0YMG1, H0YN91

UniProt curated annotations — full annotation on UniProt →

Function. 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. Acts as a molecular scaffold facilitating the interaction of PLK4 and CPAP, 2 molecules involved in centriole formation. Proposed to snatch PLK4 away from PLK4:CEP92 complexes in early G1 daughter centriole and to reposition PLK4 at the outer boundary of a newly forming CEP152 ring structure. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.

Subunit / interactions. Interacts (via N-terminus) with PLK4; the interaction is mutally exclusive with a PLK4:CEP192 interaction. Interacts (via C-terminus) with CPAP (via-N-terminus). Interacts with CINP. Interacts with CDK5RAP2, WDR62, CEP63 and CEP131. CEP63, CDK5RAP2, CEP152, WDR62 are proposed to form a stepwise assembled complex at the centrosome forming a ring near parental centrioles. Interacts with DEUP1; this interaction recruits CEP152 to the deuterosome. The interactions with CEP63 and DEUP1 are mutually exclusive. Interacts with CCDC66.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Disease relevance. Microcephaly 9, primary, autosomal recessive (MCPH9) [MIM:614852] A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals have intellectual disability. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. The disease is caused by variants affecting the gene represented in this entry. Seckel syndrome 5 (SCKL5) [MIM:613823] A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CEP152 family.

Isoforms (4)

UniProt ID	Names	Canonical?
O94986-4	4	yes
O94986-1	1
O94986-2	2
O94986-3	3

RefSeq proteins (2): NP_001181927, NP_055800 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051235	CEP152/SHC-Transforming	Family
IPR057659	CEP152_CC	Domain
IPR057664	CEP152_PLK4_bind	Binding_site

Pfam: PF25769, PF25770

UniProt features (30 total): region of interest 6, sequence variant 6, coiled-coil region 5, splice variant 4, compositionally biased region 3, helix 2, chain 1, modified residue 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6CSU	X-RAY DIFFRACTION	2.5
6CSV	X-RAY DIFFRACTION	2.5
4N7V	X-RAY DIFFRACTION	2.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94986-F1	61.54	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 1241

Mutagenesis-validated functional residues (1):

Position	Phenotype
21	impairs interaction with plk4; impaired procentriole assembly and chromosome segregation.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 313 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CENTRIOLE_ASSEMBLY, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GARY_CD5_TARGETS_DN, GOBP_COLUMNAR_CUBOIDAL_EPITHELIAL_CELL_DIFFERENTIATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_CENTROSOME_DUPLICATION, GOCC_CENTRIOLE

GO Biological Process (4): centriole replication (GO:0007099), cell projection organization (GO:0030030), centrosome duplication (GO:0051298), de novo centriole assembly involved in multi-ciliated epithelial cell differentiation (GO:0098535)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (12): pericentriolar material (GO:0000242), nucleoplasm (GO:0005654), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), nuclear body (GO:0016604), ciliary basal body (GO:0036064), deuterosome (GO:0098536), procentriole (GO:0120098), procentriole replication complex (GO:0120099), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1
M Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	4
microtubule organizing center	3
cytoplasm	3
cell cycle process	2
centrosome duplication	1
centriole assembly	1
cellular component organization	1
centrosome cycle	1
de novo centriole assembly	1
multi-ciliated epithelial cell differentiation	1
kinase binding	1
binding	1
centrosome	1
nuclear lumen	1
centriole	1
nucleoplasm	1
cilium	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

904 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP152	PLK4	O00444	992
CEP152	CDK5RAP2	Q96SN8	969
CEP152	CPAP	Q9HC77	964
CEP152	STIL	Q15468	946
CEP152	CEP63	Q96MT8	945
CEP152	CEP135	Q66GS9	942
CEP152	SASS6	Q6UVJ0	930
CEP152	ASPM	Q8IZT6	894
CEP152	CEP192	Q8TEP8	888
CEP152	MCPH1	Q8NEM0	854
CEP152	CCP110	O43303	842
CEP152	PCNT	O95613	817
CEP152	CNTLN	Q9NXG0	815
CEP152	CEP295	Q9C0D2	780
CEP152	WDR62	O43379	720

IntAct

75 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
PLK4	CEP152	psi-mi:“MI:0915”(physical association)	0.850
CEP152	PLK4	psi-mi:“MI:0915”(physical association)	0.850
PLK4	CEP152	psi-mi:“MI:0914”(association)	0.850
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
CEP131	CEP152	psi-mi:“MI:0915”(physical association)	0.500
CEP152	MOV10	psi-mi:“MI:0915”(physical association)	0.500
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
Deup1	CEP152	psi-mi:“MI:0915”(physical association)	0.400
CEP152	Cep63	psi-mi:“MI:0915”(physical association)	0.400
Cep152	CEP152	psi-mi:“MI:0915”(physical association)	0.400
CEP152	NP	psi-mi:“MI:0915”(physical association)	0.370
CEP152	E2	psi-mi:“MI:0915”(physical association)	0.370
EPB41L3	CEP152	psi-mi:“MI:0915”(physical association)	0.370
	CEP152	psi-mi:“MI:0915”(physical association)	0.370
Aurkb	SPTBN2	psi-mi:“MI:0914”(association)	0.350
PLK4	SYNPO2	psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	WDR62	psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	CEP152	psi-mi:“MI:0914”(association)	0.350
CEP152	WDR62	psi-mi:“MI:0914”(association)	0.350

BioGRID (226): CEP152 (Proximity Label-MS), CEP152 (Proximity Label-MS), CEP152 (Proximity Label-MS), CEP152 (Proximity Label-MS), CENPJ (Proximity Label-MS), CEP63 (Proximity Label-MS), PCNT (Proximity Label-MS), CDK5RAP2 (Proximity Label-MS), CEP192 (Proximity Label-MS), NEDD1 (Proximity Label-MS), GSDMA (Proximity Label-MS), MTHFD1L (Proximity Label-MS), CEP131 (Proximity Label-MS), LYAR (Proximity Label-MS), A2ML1 (Proximity Label-MS)

ESM2 similar proteins: A0JMQ7, A0JMY4, A2AUM9, A2BDR7, A2BGP7, A6NI79, A6PWD2, A6QNP9, B1AJZ9, D3YV10, G9G127, O35550, O35551, O75330, O94986, P0CB05, Q05D60, Q0VFN8, Q0VFX2, Q15276, Q17QT2, Q3UPP8, Q498G2, Q4KLY0, Q4PJT6, Q4R703, Q4V7B0, Q5JU67, Q5NVN6, Q5U3A8, Q5U3Z6, Q5U4W1, Q5ZL12, Q66KE8, Q6DFC2, Q6DIS8, Q6IMY1, Q6NRC9, Q6P402, Q7M6Y5

Diamond homologs: A2AUM9, O94986, Q498G2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK5RAP2	“up-regulates activity”	CEP152	relocalization
CEP152	“up-regulates activity”	CDK2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	8	24.4×	2e-07
Loss of proteins required for interphase microtubule organization from the centrosome	8	24.4×	2e-07
AURKA Activation by TPX2	8	23.4×	2e-07
Recruitment of mitotic centrosome proteins and complexes	8	20.9×	4e-07
Regulation of PLK1 Activity at G2/M Transition	8	19.5×	5e-07
Recruitment of NuMA to mitotic centrosomes	8	17.9×	9e-07
Anchoring of the basal body to the plasma membrane	8	17.4×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	6	65.6×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

1268 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	96
Likely pathogenic	39
Uncertain significance	373
Likely benign	593
Benign	59

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1322058	NM_001194998.2(CEP152):c.1164_1173del (p.Glu390fs)	Pathogenic
1322060	NM_001194998.2(CEP152):c.2694+1G>A	Pathogenic
1362007	NM_001194998.2(CEP152):c.1451_1452del (p.Leu483_Tyr484insTer)	Pathogenic
1456453	NC_000015.9:g.(?49073373)(49073576_?)del	Pathogenic
1460136	NM_001194998.2(CEP152):c.3658G>T (p.Glu1220Ter)	Pathogenic
158223	NM_001194998.2(CEP152):c.1155del (p.Thr386fs)	Pathogenic
158244	NM_001194998.2(CEP152):c.2679del (p.Ser894fs)	Pathogenic
1676669	NM_001194998.2(CEP152):c.2034_2036del (p.Tyr678_Gln679delinsTer)	Pathogenic
1709492	NM_001194998.2(CEP152):c.3948_3949insGGCGCAAATATTATTTG (p.Ile1317delinsGlyAlaAsnIleIleTer)	Pathogenic
210686	NM_001194998.2(CEP152):c.3014_3015delinsT (p.Lys1005fs)	Pathogenic
2117234	NM_001194998.2(CEP152):c.1783_1785delinsC (p.Thr595fs)	Pathogenic
265076	NM_001194998.2(CEP152):c.2038C>T (p.Gln680Ter)	Pathogenic
2692974	NM_001194998.2(CEP152):c.1696C>T (p.Gln566Ter)	Pathogenic
2698435	NM_001194998.2(CEP152):c.2646del (p.Glu883fs)	Pathogenic
2702221	NM_001194998.2(CEP152):c.1043del (p.His348fs)	Pathogenic
2704865	NM_001194998.2(CEP152):c.523C>T (p.Gln175Ter)	Pathogenic
2708984	NM_001194998.2(CEP152):c.3750_3754del (p.Ile1251fs)	Pathogenic
2713705	NM_001194998.2(CEP152):c.1447_1450del (p.Leu483fs)	Pathogenic
2717956	NM_001194998.2(CEP152):c.940C>T (p.Gln314Ter)	Pathogenic
2736277	NM_001194998.2(CEP152):c.927del (p.Ala310fs)	Pathogenic
2744471	NM_001194998.2(CEP152):c.2446C>T (p.Gln816Ter)	Pathogenic
2748770	NM_001194998.2(CEP152):c.2299del (p.Gln767fs)	Pathogenic
2753845	NM_001194998.2(CEP152):c.793C>T (p.Gln265Ter)	Pathogenic
2760677	NM_001194998.2(CEP152):c.764dup (p.Leu255fs)	Pathogenic
2760991	NM_001194998.2(CEP152):c.883C>T (p.Gln295Ter)	Pathogenic
2762317	NM_001194998.2(CEP152):c.2603del (p.Gly868fs)	Pathogenic
2762757	NM_001194998.2(CEP152):c.2388_2389delinsTT (p.Gln797Ter)	Pathogenic
2764801	NM_001194998.2(CEP152):c.1791_1796delinsCTTTTAATATTCAGACTAAAACTAAAATAAT (p.Asp598_Thr599delinsPheTer)	Pathogenic
2779039	NM_001194998.2(CEP152):c.1563dup (p.Ser522fs)	Pathogenic
2780515	NM_001194998.2(CEP152):c.3871C>T (p.Arg1291Ter)	Pathogenic

SpliceAI

5179 predictions. Top by Δscore:

Variant	Effect	Δscore
15:48741945:AC:A	donor_gain	1.0000
15:48741946:CC:C	donor_gain	1.0000
15:48741946:CCCTT:C	donor_gain	1.0000
15:48744234:ACTTA:A	donor_loss	1.0000
15:48744236:TTAC:T	donor_loss	1.0000
15:48744237:TA:T	donor_loss	1.0000
15:48744238:A:AC	donor_gain	1.0000
15:48744239:C:CC	donor_gain	1.0000
15:48744239:CA:C	donor_gain	1.0000
15:48744239:CAT:C	donor_gain	1.0000
15:48744239:CATT:C	donor_gain	1.0000
15:48744239:CATTT:C	donor_gain	1.0000
15:48744255:CAG:C	donor_gain	1.0000
15:48744339:ATGAC:A	acceptor_gain	1.0000
15:48744340:TGAC:T	acceptor_gain	1.0000
15:48744341:GAC:G	acceptor_gain	1.0000
15:48744342:AC:A	acceptor_gain	1.0000
15:48744343:CC:C	acceptor_gain	1.0000
15:48744344:C:CC	acceptor_gain	1.0000
15:48744988:CTCTT:C	acceptor_gain	1.0000
15:48744990:CTT:C	acceptor_gain	1.0000
15:48744990:CTTCT:C	acceptor_loss	1.0000
15:48744991:TT:T	acceptor_gain	1.0000
15:48744991:TTC:T	acceptor_loss	1.0000
15:48744992:TCT:T	acceptor_loss	1.0000
15:48744993:C:CC	acceptor_gain	1.0000
15:48745000:A:T	acceptor_gain	1.0000
15:48748094:A:C	donor_gain	1.0000
15:48748458:C:CT	donor_gain	1.0000
15:48748459:T:TT	donor_gain	1.0000

AlphaMissense

11414 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:48741980:A:G	L1319P	0.998
15:48742025:C:G	R1304P	0.997
15:48742001:C:G	R1312P	0.996
15:48741678:G:T	A1339D	0.993
15:48741669:A:G	L1342P	0.992
15:48798041:A:G	L33S	0.992
15:48742026:G:T	R1304S	0.991
15:48784014:A:G	L427P	0.991
15:48798029:A:G	L37P	0.991
15:48798050:A:G	L30S	0.991
15:48741669:A:T	L1342H	0.990
15:48742004:A:G	M1311T	0.990
15:48744245:A:G	I1277T	0.990
15:48756259:C:G	A997P	0.990
15:48756382:C:G	A956P	0.990
15:48756288:C:G	R987P	0.989
15:48760245:C:G	A862P	0.989
15:48781343:A:G	L477P	0.989
15:48782186:C:G	A456P	0.989
15:48742010:C:G	R1309P	0.988
15:48742064:C:G	R1291P	0.988
15:48756397:C:G	A951P	0.988
15:48793347:A:G	L269P	0.988
15:48741658:C:G	A1346P	0.987
15:48741980:A:T	L1319H	0.987
15:48744258:C:G	A1273P	0.987
15:48782194:A:G	L453P	0.987
15:48791349:A:G	L287P	0.987
15:48793335:A:G	L273P	0.987
15:48741679:C:G	A1339P	0.986

dbSNP variants (sampled 300 via entrez): RS1000010250 (15:48736776 T>C), RS1000028429 (15:48791482 T>A,G), RS1000169589 (15:48787168 T>TTG,TTGTTTTTG,TTGTTTTTTG), RS1000181783 (15:48733262 T>G), RS1000194544 (15:48773060 T>C), RS1000234506 (15:48763010 T>G), RS1000265727 (15:48763312 C>G), RS1000331250 (15:48769777 C>T), RS1000333726 (15:48773125 G>C,T), RS1000371105 (15:48729359 G>A), RS1000415461 (15:48784471 A>G), RS1000525033 (15:48798166 C>T), RS1000557818 (15:48757369 A>T), RS1000602937 (15:48764777 C>G,T), RS1000613525 (15:48811014 A>T)

Disease associations

OMIM: gene MIM:613529 | disease phenotypes: MIM:613823, MIM:614852, MIM:154700, MIM:210600

GenCC curated gene-disease

Disease	Classification	Inheritance
Seckel syndrome 5	Definitive	Autosomal recessive
microcephaly 9, primary, autosomal recessive	Strong	Autosomal recessive
autosomal recessive primary microcephaly	Supportive	Autosomal recessive
Seckel syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
microcephaly with or without short stature	Definitive	AR

Mondo (5): Seckel syndrome 5 (MONDO:0013443), microcephaly 9, primary, autosomal recessive (MONDO:0013923), Marfan syndrome (MONDO:0007947), Seckel syndrome (MONDO:0019342), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (5): Autosomal recessive primary microcephaly (Orphanet:2512), Seckel syndrome (Orphanet:808), Marfan syndrome type 1 (Orphanet:284963), Marfan syndrome (Orphanet:558), Microcephalic primordial dwarfism (Orphanet:324761)

HPO phenotypes

70 total (30 of 70 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000278	Retrognathia
HP:0000324	Facial asymmetry
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000369	Low-set ears
HP:0000387	Absent earlobe
HP:0000426	Prominent nasal bridge
HP:0000444	Convex nasal ridge
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000668	Hypodontia
HP:0000677	Oligodontia
HP:0000682	Abnormal dental enamel morphology
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000878	11 pairs of ribs

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_57	Obesity-related traits	5.000000e-06
GCST002052_2	Insomnia	2.000000e-06
GCST007268_50	Diastolic blood pressure	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007876	insomnia measurement
EFO:0006336	diastolic blood pressure

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008382	Marfan Syndrome	C05.116.099.674; C14.240.400.725; C14.280.400.725; C16.131.077.550; C16.131.240.400.720; C16.320.540; C17.300.500
C579935	Autosomal Recessive Primary Microcephaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Quercetin	increases expression, affects expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
incobotulinumtoxinA	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

Clinical trials (associated diseases)

58 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01295047	PHASE4	COMPLETED	Comparison of Medical Therapies in Marfan Syndrome.
NCT00429364	PHASE3	COMPLETED	Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome
NCT00485368	PHASE3	COMPLETED	Angiotensin Converting Enzyme Inhibitors in Marfan Syndrome
NCT00683124	PHASE3	UNKNOWN	Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients
NCT00723801	PHASE3	COMPLETED	Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
NCT00763893	PHASE3	TERMINATED	Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
NCT00782327	PHASE3	COMPLETED	Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
NCT01145612	PHASE3	UNKNOWN	Atenolol Versus Losartan in the Prevention of Progressive Dilation of the Aorta in Marfan Syndrome
NCT01361087	PHASE3	WITHDRAWN	Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome
NCT01715207	PHASE3	COMPLETED	Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS
NCT00593710	PHASE2	COMPLETED	Losartan Versus Atenolol for the Treatment of Marfan Syndrome
NCT00651235	PHASE2	UNKNOWN	A Randomized, Open-label, LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome
NCT01949233	PHASE2	UNKNOWN	The Oxford Marfan Trial
NCT03139903	Not specified	COMPLETED	The Primordial Dwarfisms: Diagnosis, Identification of the Molecular Basis of Seckel Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00270686	Not specified	COMPLETED	Studies of Heritable Disorders of Connective Tissue
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT01707563	Not specified	COMPLETED	Clinical Variability in Marfan Syndrome
NCT01760668	Not specified	COMPLETED	Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome
NCT02050113	Not specified	RECRUITING	Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices
NCT02111668	Not specified	COMPLETED	Thoracic Aortic Dilatation Syndromes
NCT02148900	Not specified	UNKNOWN	Development of a Blood Test for Marfan Syndrome
NCT02213484	Not specified	COMPLETED	Micro RNAs as a Marker of Aortic Aneurysm in Hereditary Aortopathy Syndromes
NCT02815072	Not specified	UNKNOWN	Generation of Marfan Syndrome and Fontan Cardiovascular Models Using Patient-specific Induced Pluripotent Stem Cells
NCT03236571	Not specified	COMPLETED	Cardiorespiratory and Muscular Rehabilitation of Children and Young Adults With Marfan Syndrome.
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT03567460	Not specified	COMPLETED	Children and Adolescents With Marfan Syndrome: 10,000 Healthy Steps and Beyond
NCT03581682	Not specified	COMPLETED	Tele-Clinic Visits in Pediatric Marfan Patients Using Parental Echo: The Future?
NCT04194619	Not specified	RECRUITING	Pregnancy in Women With Rare Multisystemic Vascular Diseases: COGRare5 Study
NCT04319107	Not specified	COMPLETED	Classifying Ectopia Lentis in Marfan Syndrome Into Five Grades of Increasing Severity
NCT04553094	Not specified	COMPLETED	Effects of Personalized Training at Home Combining Endurance and Resistance in Patients Suffering From Marfan Syndrome
NCT04641325	Not specified	COMPLETED	Marfan Syndrome Moderate Exercise Pilot
NCT04731493	Not specified	UNKNOWN	Effect on the Quality of Life of a Therapeutic Education Program in Patients With Marfan Syndrome
NCT04774172	Not specified	COMPLETED	Mortality and Morbidity Outcomes in Marfans
NCT04776668	Not specified	COMPLETED	Living With Marfan Syndrome and Your Aorta
NCT04776681	Not specified	COMPLETED	Living With Marfans and Your Aorta: Surgical Outcomes Study
NCT04970459	Not specified	RECRUITING	Biological Collection for Marfan and Related Syndromes
NCT05123339	Not specified	COMPLETED	Clinical Signs and Activity Limitations Associated With Dural Ectasia in Patients With Marfan Disease
NCT05389865	Not specified	ACTIVE_NOT_RECRUITING	Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
NCT05516043	Not specified	COMPLETED	Safety and Performance of POLYTHESE® Vascular Prosthesis