CPAP

Summary

CPAP (centrosome assembly and centriole elongation protein, HGNC:17272) is a protein-coding gene on chromosome 13q12.12-q12.13, encoding Centrosomal P4.1-associated protein (Q9HC77). Plays an important role in cell division and centrosome function by participating in centriole duplication.

This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 55835 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 6 with or without short stature (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 690 total — 47 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 61
• MANE Select transcript: NM_018451

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17272
Approved symbol	CPAP
Name	centrosome assembly and centriole elongation protein
Location	13q12.12-q12.13
Locus type	gene with protein product
Status	Approved
Aliases	LAP, LIP1, BM032, SASS4, SCKL4, Sas-4
Ensembl gene	ENSG00000151849
Ensembl biotype	protein_coding
OMIM	609279
Entrez	55835

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000381884, ENST00000418179, ENST00000471870, ENST00000493190, ENST00000545981, ENST00000616936, ENST00000868792, ENST00000926440, ENST00000926441, ENST00000926442, ENST00000926443, ENST00000926444, ENST00000926445, ENST00000926446, ENST00000926447, ENST00000926448

RefSeq mRNA: 1 — MANE Select: NM_018451 NM_018451

CCDS: CCDS9310

Canonical transcript exons

ENST00000381884 — 17 exons

Exon	Start	End
ENSE00001144808	24889316	24889400
ENSE00001144822	24899419	24899584
ENSE00001144825	24903926	24904058
ENSE00001241723	24892643	24892867
ENSE00001490143	24882279	24883369
ENSE00001607524	24911946	24912069
ENSE00001641681	24909790	24910086
ENSE00001687299	24908018	24908126
ENSE00001687868	24905346	24906960
ENSE00001699396	24907091	24907193
ENSE00001900545	24922761	24922861
ENSE00002230549	24912582	24913091
ENSE00003473109	24884323	24884463
ENSE00003538983	24885606	24885670
ENSE00003551272	24885276	24885386
ENSE00003595434	24883963	24884083
ENSE00003673233	24884161	24884245

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 95.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.8669 / max 169.6278, expressed in 1623 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136438	9.8556	1623
136437	0.0113	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.67	gold quality
left lobe of thyroid gland	UBERON:0001120	94.45	gold quality
right lobe of thyroid gland	UBERON:0001119	94.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.84	gold quality
cerebellar hemisphere	UBERON:0002245	93.63	gold quality
right testis	UBERON:0004534	93.35	gold quality
cerebellar cortex	UBERON:0002129	93.31	gold quality
thyroid gland	UBERON:0002046	93.08	gold quality
left testis	UBERON:0004533	93.03	gold quality
male germ cell	CL:0000015	92.26	gold quality
testis	UBERON:0000473	91.47	gold quality
cerebellum	UBERON:0002037	91.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.70	gold quality
ventricular zone	UBERON:0003053	89.40	gold quality
ganglionic eminence	UBERON:0004023	88.78	gold quality
body of uterus	UBERON:0009853	87.69	gold quality
right ovary	UBERON:0002118	87.18	gold quality
left ovary	UBERON:0002119	86.88	gold quality
lower esophagus mucosa	UBERON:0035834	86.73	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.89	gold quality
mucosa of transverse colon	UBERON:0004991	85.85	gold quality
primary visual cortex	UBERON:0002436	85.48	gold quality
transverse colon	UBERON:0001157	85.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.06	gold quality
lower esophagus	UBERON:0013473	85.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.05	gold quality
trabecular bone tissue	UBERON:0002483	84.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.90	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.05
E-CURD-88	no	3.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting CPAP, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-2115-5P	98.66	68.07	1191

Literature-anchored findings (GeneRIF, showing 40)

• Identifies CENPJ as LYST-interacting proteins LIP1 and LIP7, which interact with the lysosomal trafficking regulator (LYST) protein. (PMID:11984006)
• CPAP was found to augment Stat5-mediated transcription (PMID:12198240)
• CPAP carries a novel microtubule-destabilizing motif that not only inhibits microtubule nucleation from the centrosome but also depolymerizes taxol-stabilized microtubules. (PMID:15047868)
• CPAP functions as a coactivator of NF-kappaB-mediated transcription (PMID:15687488)
• Mutations in CENPJ gene is associated with autosomal recessive primary microcephaly (PMID:15793586)
• Together, our results reveal a structural role for CPAP to maintain centrosome integrity and normal spindle morphology during cell division. (PMID:16316625)
• In summary, our results show a direct interaction between CPAP and 14-3-3, and this interaction appears to be phosphorylation and cell cycle dependent. (PMID:16516142)
• discuss CENPJ, which similarly exhibits higher rate of protein evolution in primates as compared to rodents and carnivores (PMID:16631324)
• High levels of LIP1 were found in serum and synovial fluid of rheumatoid arthritis patients, providing evidence for a cytokine-like role. (PMID:18162190)
• Mutations in this conserved sequence also eliminate d-SAS-4’s microtubule-destabilizing activity, suggesting that d-SAS-4 and CPAP may play similar roles within cells. (PMID:18586240)
• the PN2-3 fragment of CPAP as a protein with an unprecedented tubulin sequestering mechanism distinct from that of stathmin family proteins. (PMID:19131341)
• Results suggest that CPAP and CP110 play antagonistic roles in determining the extent of tubulin addition during centriole elongation, thereby controlling the length of newly formed centrioles. (PMID:19481458)
• Data show that the CPAP is required for centrosome duplication in cycling human cells, and that CPAP overexpression results in the formation of abnormally long centrioles. (PMID:19481460)
• Results suggest that CPAP is a new regulator of centriole length and its intrinsic tubulin-dimer binding activity is required for procentriole elongation. (PMID:19503075)
• cell cycle-regulated phosphorylation orchestrates the dynamics of CPAP molecular interaction and centrosome splitting to ensure genomic stability in cell division (PMID:19889632)
• Data establishes that mutation of CENPJ can lead to Seckel syndrome and calls for further investigation of the role played by other microcephaly related genes in the pathogenesis of PD. (PMID:20522431)
• Results identify centrosomal P4.1-associated protein (CPAP), a human homologue of SAS-4, as a substrate of PLK2 whose activity oscillates during the cell cycle. (PMID:20531387)
• Results suggest that Cep152 recruits Plk4 and CPAP to the centrosome to ensure a faithful centrosome duplication process. (PMID:21059844)
• We conclude that the common variations we measured in the 4 microcephaly genes, ASPM, MCPH1, CDK5RAP2, and CENPJ, do not affect the risk of Alzheimer disease (PMID:21297427)
• STIL and CPAP are essential for centriole formation and for proper spindle position. (PMID:22100914)
• CPAP degradation and function is controlled by the poly(ADP-ribose) polymerase tankyrase 1. (PMID:22699936)
• SUMOylated CPAP could synergistically increase the HBx-induced NF-kappaB activity (PMID:23369793)
• Authors propose that CEP135 directly connects the central hub protein, hSAS-6, to the outer microtubules, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP-mediated centriole elongation. (PMID:23511974)
• CEP120 associates with SPICE1 and CPAP, and depletion of any of these proteins results in short procentrioles. Furthermore, CEP120 or CPAP overexpression results in excessive centriole elongation, a process dependent on CEP120, SPICE1, and CPAP. (PMID:23810536)
• CEP120 is a CPAP-interacting protein that positively regulates centriole elongation. (PMID:23857771)
• studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP-STIL interaction constitutes a conserved key step in centriole biogenesis (PMID:24052813)
• The results showed a human-specific hypomethylation in the 5’ UTR of CENPJ in the brain, where methylation levels among humans are only about one-third of those found among nonhuman primates. (PMID:24288161)
• Sas-4 acts as a vehicle to tether PCM complexes to centrioles independent of its well-known role in centriole duplication (PMID:24385583)
• CPAP depletion results in asymmetric spindle poles with uneven distribution of pericentriolar material. (PMID:24491538)
• Centrobin-CPAP interaction is critical for the recruitment of CPAP to procentrioles to promote the elongation of daughter centrioles and for the persistence of CPAP on preexisting mother centrioles. (PMID:24700465)
• Centrobin plays a role in the stability and centriole elongation function of CPAP and limits the centriole length. (PMID:25616662)
• Data suggest that the single G-box domain (that appears to fold into 14-20 antiparallel beta-strands) of CENPJ has stable but dynamic structure; CRAP forms multimers (in solution and in crystals) of elongated fibrils similar to amyloid fibrils. [REVIEW] (PMID:26517891)
• CPAP promotes timely cilium disassembly to maintain neural progenitor pool. CPAP mutation causes Seckel syndrome with microcephaly. (PMID:26929011)
• CPAP-S467D protein has a low affinity for microtubule binding but a high affinity for pericentriolar material proteins. (PMID:26997271)
• CPAP regulates delivery of its bound beta-tubulin to define the size of microtubule-based cellular structures using a “clutch-like” mechanism. (PMID:27306797)
• Data suggest that alcohol/ethanol exposure diminishes pool of proliferative neurons (Neuro2a cell line) through disordering of spindle orientation and promotion of asymmetric cell division; these neuronal abnormalities appear to be due to reduced CENPJ protein expression level. (PMID:29778912)
• CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity. (PMID:31511651)
• Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFR. (PMID:34135376)
• Identification of Pathogenic Mutations in Primary Microcephaly- (MCPH-) Related Three Genes CENPJ, CASK, and MCPH1 in Consanguineous Pakistani Families. (PMID:35281599)
• CPAP insufficiency leads to incomplete centrioles that duplicate but fragment. (PMID:35404385)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpap	ENSDARG00000018121
mus_musculus	Cpap	ENSMUSG00000064128
rattus_norvegicus	Cenpj	ENSRNOG00000022597
drosophila_melanogaster	Sas-4	FBGN0011020

Paralogs (1): TCP10L (ENSG00000242220)

Protein

Protein identifiers

Centrosomal P4.1-associated protein — Q9HC77 (reviewed: Q9HC77)

Alternative names: Centromere protein J, Centrosome assembly and centriole elongation protein, LAG-3-associated protein, LYST-interacting protein 1

All UniProt accessions (3): Q9HC77, F6VUX8, H0Y5L8

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in cell division and centrosome function by participating in centriole duplication. Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as a microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles. Required for centriole elongation and for STIL-mediated centriole amplification. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner. May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release.

Subunit / interactions. Forms homodimers. Associates with microtubules plus ends; binds to beta-tubulin subunits exposed on microtubule outer surface at its distal tip; also associates with microtubule lattice. Associated with the gamma-tubulin complex. Interacts with the head domain of EPB41. Interacts with LYST. Interacts with CEP152 (via C-terminus). Interacts with STIL. Forms a complex with STIL and SASS6.

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

Post-translational modifications. Phosphorylation at Ser-589 and Ser-595 by PLK2 is required for procentriole formation and centriole elongation. Phosphorylation by PLK2 oscillates during the cell cycle: it increases at G1/S transition and decreases during the exit from mitosis. Phosphorylation at Ser-595 is also mediated by PLK4 but is not a critical step in PLK4 function in procentriole assembly.

Disease relevance. Microcephaly 6, primary, autosomal recessive (MCPH6) [MIM:608393] 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 moderate 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 4 (SCKL4) [MIM:613676] 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 TCP10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HC77-1	1	yes
Q9HC77-2	2

RefSeq proteins (1): NP_060921* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009852	CENPJ_C_dom	Domain
IPR026581	TCP10L/CENPJ	Family
IPR047002	Tcp10_C_sf	Homologous_superfamily
IPR058029	Tubulin-bd_CENPJ	Domain

Pfam: PF07202, PF25779

UniProt features (51 total): mutagenesis site 12, region of interest 9, sequence variant 7, compositionally biased region 6, modified residue 6, sequence conflict 4, helix 3, splice variant 2, chain 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5EIB	X-RAY DIFFRACTION	2.1
5ITZ	X-RAY DIFFRACTION	2.2
7Q1F	X-RAY DIFFRACTION	2.35
7Z0F	X-RAY DIFFRACTION	2.4
7Q1E	X-RAY DIFFRACTION	2.7
7Z0G	X-RAY DIFFRACTION	3.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC77-F1	56.70	0.24

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 (6): 260, 316, 540, 589, 595, 759

Mutagenesis-validated functional residues (12):

Position	Phenotype
338	decreases interaction with alpha/beta-tubulin; when associated with a-339 and a-341.
339	decreases interaction with alpha/beta-tubulin; when associated with a-338 and a-341.
341	decreases interaction with alpha/beta-tubulin; when associated with a-338 and a-339.
343	slightly decreases interaction with alpha/beta-tubulin; causes overly long daughter centrioles and enhances ciliary leng
344	slightly decreases interaction with alpha/beta-tubulin; causes overly long daughter centrioles and enhances ciliary leng
375	decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on associatio
375	strongly decreases interaction with alpha/beta-tubulin; causes shorter centrioles and doublet microtubules in cilia.
377	decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on associatio
378	decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on associatio
385	decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on associatio
589	abolishes phosphorylation by plk2 and procentriole formation; when associated with a-595.
595	abolishes phosphorylation by plk2 and procentriole formation; when associated with a-589.

Function

Pathways and Gene Ontology

Reactome pathways

8 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-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 404 (showing top): GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_MICROTUBULE_NUCLEATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_CENTRIOLE_REPLICATION, GOBP_CENTRIOLE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (23): microtubule nucleation (GO:0007020), centriole replication (GO:0007099), smoothened signaling pathway (GO:0007224), astral microtubule nucleation (GO:0030954), motile cilium assembly (GO:0044458), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), regulation of centriole replication (GO:0046599), positive regulation of centriole replication (GO:0046601), microtubule polymerization (GO:0046785), cell division (GO:0051301), regulation of mitotic spindle organization (GO:0060236), cilium assembly (GO:0060271), centriole elongation (GO:0061511), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of non-motile cilium assembly (GO:1902857), positive regulation of centriole elongation (GO:1903724), positive regulation of establishment of protein localization (GO:1904951), non-motile cilium assembly (GO:1905515), positive regulation of spindle assembly (GO:1905832), positive regulation of DNA-templated transcription (GO:0045893), centrosome duplication (GO:0051298), centriole assembly (GO:0098534), positive regulation of organelle assembly (GO:1902117)

GO Molecular Function (7): transcription coactivator activity (GO:0003713), tubulin binding (GO:0015631), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), gamma-tubulin binding (GO:0043015), protein binding (GO:0005515)

GO Cellular Component (10): acrosomal vesicle (GO:0001669), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), microtubule (GO:0005874), gamma-tubulin small complex (GO:0008275), ciliary basal body (GO:0036064), procentriole replication complex (GO:0120099), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
TP53 Regulates Transcription of Cell Cycle Genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
centriole replication	3
microtubule organizing center	3
cell cycle process	2
cilium assembly	2
positive regulation of cytoskeleton organization	2
positive regulation of cell cycle process	2
positive regulation of organelle assembly	2
protein binding	2
cellular anatomical structure	2
intracellular membraneless organelle	2
cytoplasm	2
microtubule cytoskeleton organization	1
microtubule polymerization	1
centrosome duplication	1
centriole assembly	1
cell surface receptor signaling pathway	1
astral microtubule organization	1
microtubule nucleation by microtubule organizing center	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
regulation of centrosome duplication	1
regulation of organelle assembly	1
regulation of centriole replication	1
microtubule nucleation	1
microtubule polymerization or depolymerization	1
protein polymerization	1
supramolecular fiber organization	1
cellular process	1
mitotic spindle organization	1
regulation of spindle organization	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
G1/S transition of mitotic cell cycle	1

Protein interactions and networks

STRING

1899 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPAP	CEP135	Q66GS9	993
CPAP	SASS6	Q6UVJ0	989
CPAP	PLK4	O00444	982
CPAP	CEP152	O94986	964
CPAP	CCP110	O43303	962
CPAP	CDK5RAP2	Q96SN8	948
CPAP	STIL	Q15468	940
CPAP	ASPM	Q8IZT6	927
CPAP	MCPH1	Q8NEM0	916
CPAP	TUBG1	P23258	875
CPAP	CNTLN	Q9NXG0	874
CPAP	PCNT	O95613	852
CPAP	HYLS1	Q96M11	829
CPAP	WDR62	O43379	823
CPAP	CEP63	Q96MT8	780
CPAP	CEP192	Q8TEP8	780

IntAct

98 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
CPAP	STIL	psi-mi:“MI:0407”(direct interaction)	0.820
CPAP	STIL	psi-mi:“MI:0914”(association)	0.820
STIL	CPAP	psi-mi:“MI:0915”(physical association)	0.820
CPAP	STIL	psi-mi:“MI:0915”(physical association)	0.820
STIL	CPAP	psi-mi:“MI:0407”(direct interaction)	0.820
YWHAG	CPAP	psi-mi:“MI:0914”(association)	0.720
SLMAP	STRN	psi-mi:“MI:2364”(proximity)	0.710
CEP135	CPAP	psi-mi:“MI:0403”(colocalization)	0.700
CPAP	CEP135	psi-mi:“MI:0914”(association)	0.700
CPAP	CEP135	psi-mi:“MI:0915”(physical association)	0.700
CEP135	CPAP	psi-mi:“MI:0915”(physical association)	0.700
CPAP	CEP135	psi-mi:“MI:0407”(direct interaction)	0.700
CEP135	CPAP	psi-mi:“MI:0407”(direct interaction)	0.700
SASS6	STIL	psi-mi:“MI:0914”(association)	0.650
STIL	SASS6	psi-mi:“MI:0914”(association)	0.650
SASS6	CEP135	psi-mi:“MI:0914”(association)	0.650
CPAP	CPAP	psi-mi:“MI:0407”(direct interaction)	0.620

BioGRID (245): CENPJ (Affinity Capture-RNA), CENPJ (Affinity Capture-RNA), CENPJ (Two-hybrid), CENPJ (Affinity Capture-Western), CENPJ (Reconstituted Complex), CREBBP (Reconstituted Complex), CREBBP (Phenotypic Enhancement), CENPJ (Affinity Capture-MS), CEP55 (Proximity Label-MS), CEP131 (Proximity Label-MS), NEDD1 (Proximity Label-MS), PLK1 (Proximity Label-MS), CEP120 (Proximity Label-MS), CCP110 (Proximity Label-MS), CEP85 (Proximity Label-MS)

ESM2 similar proteins: A0A087WRU1, A0JNH1, A2RUB1, A6QNQ6, B0S6S9, B1WC58, D3Z987, D3ZJ47, E1BC15, O60673, P28358, P28359, P56716, P70347, Q0P5X5, Q0VAV2, Q0VBV7, Q15468, Q2M2Z5, Q3UXL4, Q3V089, Q49A88, Q569L8, Q5BQN8, Q5CZC0, Q5QGS0, Q5T1N1, Q5VWN6, Q60988, Q61493, Q62924, Q6ZP01, Q6ZU52, Q6ZVD7, Q80U59, Q80WQ8, Q86WS4, Q86YC2, Q8CB14, Q8IUR6

Diamond homologs: Q569L8, Q5BQN8, Q9HC77

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PLK2	up-regulates	CENPJ	phosphorylation
PLK4	up-regulates	CENPJ	phosphorylation
CEP135	“up-regulates activity”	CENPJ	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Activation of BAD and translocation to mitochondria	5	71.8×	5e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	63.4×	8e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	63.4×	8e-08
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	6	61.6×	6e-09
Transport of connexons to the plasma membrane	6	61.6×	6e-09
Gap junction trafficking and regulation	6	53.9×	1e-08
Gap junction trafficking	6	53.9×	1e-08
Activation of BH3-only proteins	5	46.8×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	5	50.2×	7e-06
mitotic spindle organization	9	33.5×	3e-09
mitotic spindle assembly	6	28.3×	8e-06
microtubule cytoskeleton organization	11	18.3×	4e-09
memory	5	12.6×	2e-03
mitotic cell cycle	6	11.0×	8e-04
intracellular protein localization	6	8.6×	2e-03
protein phosphorylation	7	6.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	18
Uncertain significance	286
Likely benign	201
Benign	55

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1032801	NM_018451.5(CPAP):c.1434del (p.Lys479fs)	Pathogenic
1032802	NM_018451.5(CPAP):c.2117_2118del (p.Asp705_Ser706insTer)	Pathogenic
1069283	NM_018451.5(CPAP):c.407_411del (p.Gly136fs)	Pathogenic
1322056	NM_018451.5(CPAP):c.931del (p.Gln311fs)	Pathogenic
1355246	NM_018451.5(CPAP):c.3539_3542del (p.Glu1180fs)	Pathogenic
1404326	NM_018451.5(CPAP):c.1749del (p.Ala584fs)	Pathogenic
1453667	NM_018451.5(CPAP):c.125_126del (p.Lys42fs)	Pathogenic
1456229	NM_018451.5(CPAP):c.3313C>T (p.Arg1105Ter)	Pathogenic
1527750	GRCh37/hg19 13q11-34(chr13:19436286-115107733)	Pathogenic
1817	NM_018451.5(CPAP):c.18del (p.Ser7fs)	Pathogenic
1818	NM_018451.5(CPAP):c.3704A>T (p.Glu1235Val)	Pathogenic
1964703	NM_018451.5(CPAP):c.3100_3103del (p.Glu1034fs)	Pathogenic
2005320	NM_018451.5(CPAP):c.3237_3255del (p.Asn1080fs)	Pathogenic
2024821	NM_018451.5(CPAP):c.2197C>T (p.Gln733Ter)	Pathogenic
2096159	NM_018451.5(CPAP):c.1561C>T (p.Gln521Ter)	Pathogenic
210655	NM_018451.5(CPAP):c.1339A>T (p.Lys447Ter)	Pathogenic
210657	NM_018451.5(CPAP):c.1404_1407del (p.Ser469fs)	Pathogenic
210658	NM_018451.5(CPAP):c.1850_1851del (p.Pro617fs)	Pathogenic
210660	NM_018451.5(CPAP):c.1882del (p.Ala628fs)	Pathogenic
210665	NM_018451.5(CPAP):c.3007dup (p.Ile1003fs)	Pathogenic
2308060	NM_018451.5(CPAP):c.2328dup (p.Val777fs)	Pathogenic
2776677	NM_018451.5(CPAP):c.3276C>G (p.Tyr1092Ter)	Pathogenic
279750	NM_018451.5(CPAP):c.289dup (p.Thr97fs)	Pathogenic
280477	NM_018451.5(CPAP):c.129_130del (p.Lys44fs)	Pathogenic
280490	NM_018451.5(CPAP):c.1029del (p.Glu344fs)	Pathogenic
2843599	NM_018451.5(CPAP):c.3630_3643del (p.Ala1211fs)	Pathogenic
288549	NM_018451.5(CPAP):c.1681_1684del (p.Leu561fs)	Pathogenic
2890716	NM_018451.5(CPAP):c.2283dup (p.Asp762fs)	Pathogenic
2911250	NM_018451.5(CPAP):c.669C>G (p.Tyr223Ter)	Pathogenic
3009434	NM_018451.5(CPAP):c.2746_2747del (p.Glu916fs)	Pathogenic

SpliceAI

3131 predictions. Top by Δscore:

Variant	Effect	Δscore
13:24883367:TCA:T	acceptor_gain	1.0000
13:24883368:CA:C	acceptor_gain	1.0000
13:24883368:CAC:C	acceptor_gain	1.0000
13:24883370:C:CC	acceptor_gain	1.0000
13:24884084:C:CC	acceptor_gain	1.0000
13:24884163:A:AC	donor_gain	1.0000
13:24884164:T:C	donor_gain	1.0000
13:24884190:T:TA	donor_gain	1.0000
13:24884322:CCA:C	donor_gain	1.0000
13:24884322:CCACT:C	donor_gain	1.0000
13:24884463:CCTA:C	acceptor_loss	1.0000
13:24884464:CTAA:C	acceptor_loss	1.0000
13:24884465:T:C	acceptor_loss	1.0000
13:24884574:T:A	donor_gain	1.0000
13:24884575:C:A	donor_gain	1.0000
13:24884586:T:TA	donor_gain	1.0000
13:24885279:T:A	donor_gain	1.0000
13:24885301:C:CA	donor_gain	1.0000
13:24885604:A:AC	donor_gain	1.0000
13:24885605:C:CC	donor_gain	1.0000
13:24885610:C:A	donor_gain	1.0000
13:24885615:AT:A	donor_gain	1.0000
13:24907086:CTGA:C	donor_loss	1.0000
13:24907087:TGA:T	donor_loss	1.0000
13:24907088:GACCT:G	donor_loss	1.0000
13:24907090:C:G	donor_loss	1.0000
13:24907189:TGGGC:T	acceptor_gain	1.0000
13:24907190:GGGC:G	acceptor_gain	1.0000
13:24907191:GGC:G	acceptor_gain	1.0000
13:24907192:GC:G	acceptor_gain	1.0000

AlphaMissense

8937 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:24883301:C:G	R1298P	0.999
13:24883276:T:A	K1306N	0.997
13:24883276:T:G	K1306N	0.997
13:24906288:C:G	A584P	0.996
13:24906304:A:C	F578L	0.996
13:24906304:A:T	F578L	0.996
13:24906306:A:G	F578L	0.996
13:24883229:C:G	R1322P	0.995
13:24883345:A:C	F1283L	0.995
13:24883345:A:T	F1283L	0.995
13:24883347:A:G	F1283L	0.995
13:24892746:A:G	L1038P	0.995
13:24883216:C:A	K1326N	0.994
13:24883216:C:G	K1326N	0.994
13:24883222:T:A	R1324S	0.994
13:24883222:T:G	R1324S	0.994
13:24906285:C:G	A585P	0.994
13:24906262:A:C	S592R	0.993
13:24906262:A:T	S592R	0.993
13:24906264:T:G	S592R	0.993
13:24906305:A:G	F578S	0.993
13:24883253:T:G	Q1314P	0.992
13:24883302:G:C	R1298G	0.992
13:24883346:A:G	F1283S	0.992
13:24892788:A:G	L1024P	0.992
13:24906296:A:G	L581S	0.992
13:24883306:C:A	K1296N	0.991
13:24883306:C:G	K1296N	0.991
13:24883975:A:T	V1271D	0.991
13:24884177:G:C	F1229L	0.991

dbSNP variants (sampled 300 via entrez): RS1000099968 (13:24909497 C>T), RS1000135389 (13:24920012 T>C), RS1000238682 (13:24941088 G>T), RS1000273351 (13:24921790 G>A), RS1000346866 (13:24886461 A>G), RS1000390666 (13:24892995 A>G), RS1000403821 (13:24915659 G>A), RS1000434690 (13:24917545 T>G), RS1000435759 (13:24911537 T>C), RS1000481194 (13:24928209 A>C,T), RS1000512121 (13:24882693 T>TAATA), RS1000512956 (13:24923864 T>C,G), RS1000554566 (13:24892392 G>A), RS1000781363 (13:24911050 A>G), RS1000807290 (13:24917184 G>T)

Disease associations

OMIM: gene MIM:609279 | disease phenotypes: MIM:613676, MIM:608393, MIM:156000, MIM:251200, MIM:607432, MIM:210600, MIM:613823

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 6 with or without short stature	Definitive	Autosomal recessive
microcephaly 6, primary, autosomal recessive	Definitive	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 6 with or without short stature	Definitive	AR

Mondo (12): Seckel syndrome 4 (MONDO:0013358), microcephaly 6, primary, autosomal recessive (MONDO:0012029), Meniere disease (MONDO:0007972), microcephaly 1, primary, autosomal recessive (MONDO:0009617), microcephaly (MONDO:0001149), lissencephaly spectrum disorders (MONDO:0018838), autosomal recessive primary microcephaly (MONDO:0016660), Seckel syndrome 1 (MONDO:0008869), lissencephaly type 3 (MONDO:0015148), Seckel syndrome 5 (MONDO:0013443), microcephaly 6 with or without short stature (MONDO:0700054), Seckel syndrome (MONDO:0019342)

Orphanet (6): Seckel syndrome (Orphanet:808), Autosomal recessive primary microcephaly (Orphanet:2512), Lissencephaly (Orphanet:48471), Lissencephaly type 3 (Orphanet:102011), NON RARE IN EUROPE: Menière disease (Orphanet:45360), Premature chromosome condensation with microcephaly and intellectual disability (Orphanet:52183)

HPO phenotypes

61 total (30 of 61 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000363	Abnormal earlobe morphology
HP:0000369	Low-set ears
HP:0000387	Absent earlobe
HP:0000430	Underdeveloped nasal alae
HP:0000444	Convex nasal ridge
HP:0000456	Bifid nasal tip
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000582	Upslanted palpebral fissure
HP:0000682	Abnormal dental enamel morphology
HP:0000878	11 pairs of ribs
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001344	Absent speech

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002987_26	Stroke	5.000000e-07

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499
D008575	Meniere Disease	C09.218.568.217.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C579935	Autosomal Recessive Primary Microcephaly (supp.)
C565384	Microcephaly, Primary Autosomal Recessive, 1 (supp.)
C564247	Microcephaly, Primary Autosomal Recessive, 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Testosterone	decreases expression, affects cotreatment	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sulforaphane	decreases methylation, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
flavone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	increases expression, increases abundance	1
Calcitriol	decreases expression, affects cotreatment	1
Coumestrol	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT03139903	Not specified	COMPLETED	The Primordial Dwarfisms: Diagnosis, Identification of the Molecular Basis of Seckel Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT05582148	Not specified	UNKNOWN	Meniere Disease and Hearing Aids
NCT05844657	Not specified	COMPLETED	Comprehensive Evaluation in Patients With Meniere’s Disease
NCT05960786	Not specified	COMPLETED	Treating the Symptoms of Vertigo in a Real-world Setting Using the OtoBand
NCT06278129	Not specified	UNKNOWN	Evaluation of the Diagnostic and Prognostic Efficacy of MRI in Acute Sensorineural Hearing Loss and Ménière’s Disease
NCT06544590	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT07272473	Not specified	RECRUITING	Effects of Cervical Mobilization on Dizziness, Balance, and Joint Position Sense in Patients With Meniere’s Disease
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)