CEP63

Summary

CEP63 (centrosomal protein 63, HGNC:25815) is a protein-coding gene on chromosome 3q22.2, encoding Centrosomal protein of 63 kDa (Q96MT8). Required for normal spindle assembly.

This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined.

Source: NCBI Gene 80254 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Seckel syndrome 6 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 25
• Clinical variants (ClinVar): 528 total — 26 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_001353108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25815
Approved symbol	CEP63
Name	centrosomal protein 63
Location	3q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13386
Ensembl gene	ENSG00000182923
Ensembl biotype	protein_coding
OMIM	614724
Entrez	80254

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 60 protein_coding, 12 nonsense_mediated_decay, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000332047, ENST00000354446, ENST00000383229, ENST00000504013, ENST00000504929, ENST00000508778, ENST00000510625, ENST00000511574, ENST00000512894, ENST00000513295, ENST00000513612, ENST00000514678, ENST00000606977, ENST00000620544, ENST00000650279, ENST00000675561, ENST00000682007, ENST00000682013, ENST00000682042, ENST00000682072, ENST00000682111, ENST00000682190, ENST00000682316, ENST00000682388, ENST00000682402, ENST00000682458, ENST00000682593, ENST00000682670, ENST00000682685, ENST00000682689, ENST00000682717, ENST00000682800, ENST00000682822, ENST00000682858, ENST00000682937, ENST00000682954, ENST00000683019, ENST00000683118, ENST00000683138, ENST00000683177, ENST00000683190, ENST00000683245, ENST00000683556, ENST00000683596, ENST00000683608, ENST00000683732, ENST00000683861, ENST00000683931, ENST00000683940, ENST00000683949, ENST00000683997, ENST00000684060, ENST00000684170, ENST00000684217, ENST00000684256, ENST00000684411, ENST00000684481, ENST00000684492, ENST00000684574, ENST00000684588, ENST00000684677, ENST00000684777, ENST00000891598, ENST00000891599, ENST00000891600, ENST00000891601, ENST00000891602, ENST00000891603, ENST00000891604, ENST00000924588, ENST00000924589, ENST00000924590, ENST00000924591, ENST00000948198, ENST00000948199, ENST00000948200, ENST00000948201, ENST00000948202, ENST00000948203, ENST00000948204

RefSeq mRNA: 20 — MANE Select: NM_001353108 NM_001042383, NM_001042384, NM_001042400, NM_001353108, NM_001353109, NM_001353110, NM_001353111, NM_001353112, NM_001353113, NM_001353117, NM_001353118, NM_001353119, NM_001353120, NM_001353121, NM_001353122, NM_001353123, NM_001353124, NM_001353125, NM_001353126, NM_025180

CCDS: CCDS3086, CCDS43152, CCDS43153, CCDS43154, CCDS93388, CCDS93389, CCDS93392

Canonical transcript exons

ENST00000675561 — 15 exons

Exon	Start	End
ENSE00001291043	134547335	134547472
ENSE00001296631	134558142	134558347
ENSE00001296774	134545586	134545819
ENSE00001307112	134537155	134537268
ENSE00001310297	134551926	134552012
ENSE00001317797	134559150	134559429
ENSE00001318321	134546149	134546288
ENSE00001319107	134549062	134549176
ENSE00001330563	134532778	134532900
ENSE00002056362	134486057	134486202
ENSE00003480774	134531845	134531940
ENSE00003614136	134495296	134495364
ENSE00003669073	134507109	134507286
ENSE00003680320	134550063	134550260
ENSE00003698058	134561377	134565031

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0978 / max 617.2054, expressed in 1801 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38708	6.1514	1676
38712	4.6554	1510
38710	3.6190	1353
38711	1.9293	1045
38709	1.2140	562
38714	0.8203	195
38715	0.7917	279
38713	0.5758	232
38716	0.3409	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.54	gold quality
colonic epithelium	UBERON:0000397	93.01	gold quality
cortical plate	UBERON:0005343	92.99	gold quality
sural nerve	UBERON:0015488	92.94	gold quality
tendon	UBERON:0000043	91.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.74	gold quality
monocyte	CL:0000576	91.59	gold quality
left testis	UBERON:0004533	91.49	gold quality
gastrocnemius	UBERON:0001388	91.43	gold quality
mononuclear cell	CL:0000842	91.38	gold quality
ganglionic eminence	UBERON:0004023	91.36	gold quality
muscle of leg	UBERON:0001383	91.30	gold quality
leukocyte	CL:0000738	91.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.02	gold quality
right testis	UBERON:0004534	90.92	gold quality
blood	UBERON:0000178	90.89	gold quality
testis	UBERON:0000473	90.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.32	gold quality
bone marrow cell	CL:0002092	90.13	gold quality
popliteal artery	UBERON:0002250	90.06	gold quality
tibial artery	UBERON:0007610	90.06	gold quality
cartilage tissue	UBERON:0002418	89.61	gold quality
muscle organ	UBERON:0001630	89.51	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.36	gold quality
biceps brachii	UBERON:0001507	89.31	gold quality
right atrium auricular region	UBERON:0006631	89.14	gold quality
tibia	UBERON:0000979	89.09	gold quality
islet of Langerhans	UBERON:0000006	88.84	gold quality
aorta	UBERON:0000947	88.46	gold quality
cardiac atrium	UBERON:0002081	88.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.09
E-MTAB-6379	no	224.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting CEP63, 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-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 14)

• CEP63 transcripts exhibited three different expression patterns, downregulation was found in about 50% of the cases analyzed and CEP63 gene transcription was associated with invasive tumors. (PMID:16410684)
• Findings define Cep63 as a centrosomal recruitment factor for Cdk1 that is essential for mitotic entry, providing a physical link between the centrosome and the cell-cycle machinery. (PMID:21406398)
• One new SNP (rs112926188) in CEP63O was reported. Analysis showed that rs112926188 allele substituting proline at the 61st residue position of CEP63 produced more flexibility in three-deimensional space. (PMID:22555018)
• Cep57, Cep63, and Cep152 are parts of a ring-like complex localizing around the proximal end of centrioles. (PMID:23333316)
• 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)
• centrosomal Cdk1 signals were strongly diminished in cells treated with Cep63 siRNA when sc-54 was used for Cdk1 labeling (PMID:25643699)
• CEP63 is particularly important for brain development and might control the proliferation and migration of cells when those two events need to be highly coordinated. (PMID:26400686)
• 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)
• CCDC57 Cooperates with Microtubules and Microcephaly Protein CEP63 and Regulates Centriole Duplication and Mitotic Progression. (PMID:32402286)
• [Study on Cep63 expression and apoptosis of thyroid papillary carcinoma cell lines TPC-1]. (PMID:33472304)
• 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)
• Cep63 knockout inhibits the malignant phenotypes of papillary thyroid cancer cell line TPC1. (PMID:34296302)
• CEP63 upregulates YAP1 to promote colorectal cancer progression through stabilizing RNA binding protein FXR1. (PMID:35989368)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep63	ENSDARG00000056862
mus_musculus	Cep63	ENSMUSG00000032534
rattus_norvegicus	Cep63	ENSRNOG00000008410

Paralogs (2): CCDC18 (ENSG00000122483), DEUP1 (ENSG00000165325)

Protein

Protein identifiers

Centrosomal protein of 63 kDa — Q96MT8 (reviewed: Q96MT8)

All UniProt accessions (26): Q96MT8, A0A3B3IT05, A0A804HHU4, A0A804HI22, A0A804HI78, A0A804HIX3, A0A804HJ63, A0A804HJ73, A0A804HJF1, A0A804HJF9, A0A804HJI5, A0A804HJP1, A0A804HJT2, A0A804HK67, A0A804HKF0, A0A804HKH7, A0A804HKK0, A0A804HKM0, A0A804HKQ7, A0A804HKR1, A0A804HL17, D6R9Q4, D6RAY6, H0Y900, H0YAE6, H0YAL1

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication. Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned. Also recruits CDK1 to centrosomes. Plays a role in DNA damage response. Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression. Promotes stabilization of FXR1 protein by inhibiting FXR1 ubiquitination.

Subunit / interactions. Interacts with CEP152 and CDK1; these interactions recruit both ligands to centrosomes. Interacts with CDK2, CDK5RAP2, WDR62, CEP90, KIAA0753/moonraker and CCDC14. CEP63, CDK5RAP2, CEP152, WDR62 are proposed to form a stepwise assembled complex at the centrosome forming a ring near parental centrioles. Interacts with CCDC57; the interaction is required for their location to proximal end of centrioles. Interacts with FXR1; promoting its stabilization. (Microbial infection) Interacts with zika virus serine protease NS3; this interaction disorganizes the centrosome.

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

Post-translational modifications. Polyubiquitinated via ‘Lys-48’-linked ubiquitin, leading to its degradation. Deubiquitinated by USP36, promoting its stabilization.

Disease relevance. Seckel syndrome 6 (SCKL6) [MIM:614728] 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.

Miscellaneous. CEP63 and DEUP1 paralogs are both involved in centriole amplification: while CEP63 mediates mother-centriole-dependent centriole duplication, DEUP1 mediates de novo centriole amplification in multiciliated cells.

Similarity. Belongs to the CEP63 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96MT8-1	1	yes
Q96MT8-2	2
Q96MT8-3	3
Q96MT8-4	4

RefSeq proteins (20): NP_001035842, NP_001035843, NP_001035859, NP_001340037, NP_001340038, NP_001340039, NP_001340040, NP_001340041, NP_001340042, NP_001340046, NP_001340047, NP_001340048, NP_001340049, NP_001340050, NP_001340051, NP_001340052, NP_001340053, NP_001340054, NP_001340055, NP_079456 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031470	CEP63/Deup1_N	Domain
IPR057656	CEP63/Deup1_CC	Domain

Pfam: PF17045, PF25771

UniProt features (15 total): coiled-coil region 4, splice variant 4, helix 2, modified residue 2, chain 1, sequence variant 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
7W91	X-RAY DIFFRACTION	3.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MT8-F1	77.95	0.59

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 (2): 1, 278

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: 241 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_CENTRIOLE_ASSEMBLY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_REGULATION_OF_RESPONSE_TO_STRESS

GO Biological Process (12): DNA damage checkpoint signaling (GO:0000077), centriole replication (GO:0007099), signal transduction in response to DNA damage (GO:0042770), negative regulation of innate immune response (GO:0045824), protein stabilization (GO:0050821), spindle assembly (GO:0051225), cell division (GO:0051301), de novo centriole assembly involved in multi-ciliated epithelial cell differentiation (GO:0098535), negative regulation of protein K63-linked ubiquitination (GO:1900045), DNA damage response (GO:0006974), proteasomal protein catabolic process (GO:0010498), innate immune response (GO:0045087)

GO Molecular Function (2): molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (9): spindle pole (GO:0000922), nucleoplasm (GO:0005654), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), 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
microtubule organizing center	3
binding	2
intracellular membraneless organelle	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
cell cycle process	1
centrosome duplication	1
centriole assembly	1
DNA damage response	1
intracellular signal transduction	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
regulation of protein stability	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
cellular process	1
de novo centriole assembly	1
multi-ciliated epithelial cell differentiation	1
protein K63-linked ubiquitination	1
regulation of protein K63-linked ubiquitination	1
negative regulation of protein polyubiquitination	1
cellular response to stress	1
protein catabolic process	1
immune response	1
defense response to symbiont	1
molecular_function	1
spindle	1
nuclear lumen	1
centriole	1
cytoplasm	1
centrosome	1
cilium	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP63	CEP152	O94986	945
CEP63	CEP57	Q86XR8	856
CEP63	WDR62	O43379	849
CEP63	PLK4	O00444	838
CEP63	CEP192	Q8TEP8	834
CEP63	STIL	Q15468	796
CEP63	CEP135	Q66GS9	794
CEP63	KIAA0753	Q2KHM9	789
CEP63	CCDC14	Q49A88	786
CEP63	CDK5RAP2	Q96SN8	785
CEP63	CPAP	Q9HC77	780
CEP63	ASPM	Q8IZT6	765
CEP63	SASS6	Q6UVJ0	762
CEP63	CEP120	Q8N960	702
CEP63	PCNT	O95613	687

IntAct

165 interactions, top by confidence:

A	B	Type	Score
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
PIBF1	CEP63	psi-mi:“MI:0915”(physical association)	0.760
DTNB	CEP63	psi-mi:“MI:0915”(physical association)	0.740
CEP57	CEP63	psi-mi:“MI:0915”(physical association)	0.740
CEP63	TBC1D15	psi-mi:“MI:0915”(physical association)	0.740
TBC1D15	CEP63	psi-mi:“MI:0915”(physical association)	0.740
CEP63	CEP57	psi-mi:“MI:0915”(physical association)	0.740
CEP63	DTNB	psi-mi:“MI:0915”(physical association)	0.740
PIBF1	PCM1	psi-mi:“MI:0914”(association)	0.720
CCDC14	CEP63	psi-mi:“MI:0915”(physical association)	0.710
Cep152	CEP63	psi-mi:“MI:0915”(physical association)	0.690
ALOX5	CEP63	psi-mi:“MI:0915”(physical association)	0.670
CEP63	EZH2	psi-mi:“MI:0915”(physical association)	0.670
TXLNB	CEP63	psi-mi:“MI:0915”(physical association)	0.670
SMARCE1	CEP63	psi-mi:“MI:0915”(physical association)	0.670
CEP63	SSX3	psi-mi:“MI:0915”(physical association)	0.670
CEP63	TXLNB	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (264): CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid), CEP63 (Two-hybrid)

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: B9V5F5, F7DP49, P0CB05, Q3UPP8, Q4KLY0, Q4R703, Q5HZK9, Q5NVN6, Q6PGZ0, Q96MT8, Q05D60, Q95JK1, Q5U3Z6, Q7M6Y5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK5RAP2	“up-regulates activity”	CEP63	relocalization
CEP63	“up-regulates activity”	CDK2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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	6	19.8×	6e-05
Loss of proteins required for interphase microtubule organization from the centrosome	6	19.8×	6e-05
AURKA Activation by TPX2	6	19.0×	6e-05
Recruitment of mitotic centrosome proteins and complexes	6	17.0×	9e-05
Anchoring of the basal body to the plasma membrane	7	16.5×	6e-05
Regulation of PLK1 Activity at G2/M Transition	6	15.9×	1e-04
Recruitment of NuMA to mitotic centrosomes	6	14.6×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment of mitotic spindle orientation	5	34.4×	2e-04
intermediate filament organization	5	17.2×	2e-03
cilium assembly	8	8.4×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	19
Uncertain significance	254
Likely benign	122
Benign	66

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1206034	NM_001353108.3(CEP63):c.990del (p.Asp330fs)	Pathogenic
1380648	NM_001353108.3(CEP63):c.1722C>A (p.Tyr574Ter)	Pathogenic
1441092	NM_001353108.3(CEP63):c.577C>T (p.Gln193Ter)	Pathogenic
1453008	NM_001353108.3(CEP63):c.1189G>T (p.Glu397Ter)	Pathogenic
1905565	NM_001353108.3(CEP63):c.880C>T (p.Gln294Ter)	Pathogenic
1924575	NM_001353108.3(CEP63):c.1608dup (p.Gln537fs)	Pathogenic
2019176	NM_001353108.3(CEP63):c.240del (p.Gln80fs)	Pathogenic
2073767	NM_001353108.3(CEP63):c.764T>A (p.Leu255Ter)	Pathogenic
2096488	NM_001353108.3(CEP63):c.1473del (p.Glu492fs)	Pathogenic
2143588	NM_001353108.3(CEP63):c.538C>T (p.Gln180Ter)	Pathogenic
2426929	NC_000003.11:g.(?134225951)(134251742_?)del	Pathogenic
254181	NM_178554.6(KY):c.405C>A (p.Tyr135Ter)	Pathogenic
2581449	NM_178554.6(KY):c.481C>T (p.Gln161Ter)	Pathogenic
2581612	NM_001353108.3(CEP63):c.490C>T (p.Gln164Ter)	Pathogenic
2707896	NM_001353108.3(CEP63):c.987dup (p.Asp330fs)	Pathogenic
2777203	NM_001353108.3(CEP63):c.1201C>T (p.Gln401Ter)	Pathogenic
2815946	NM_001353108.3(CEP63):c.1159G>T (p.Glu387Ter)	Pathogenic
2879456	NM_001353108.3(CEP63):c.718del (p.Thr240fs)	Pathogenic
2988763	NM_001353108.3(CEP63):c.1279C>T (p.Arg427Ter)	Pathogenic
35517	NM_001353108.3(CEP63):c.129G>A (p.Trp43Ter)	Pathogenic
3624126	NM_001353108.3(CEP63):c.584T>G (p.Leu195Ter)	Pathogenic
3661692	NM_001353108.3(CEP63):c.1191_1195del (p.Glu397fs)	Pathogenic
402246	NM_178554.6(KY):c.51_52insTATCGACATGTGCTGTATCTATCGACAT (p.Val18fs)	Pathogenic
4753151	NM_001353108.3(CEP63):c.1154dup (p.Asn385fs)	Pathogenic
520721	NM_001353108.3(CEP63):c.448del (p.Arg150fs)	Pathogenic
997854	NM_178554.6(KY):c.415C>T (p.Arg139Ter)	Pathogenic
1120220	NM_001353108.3(CEP63):c.1125T>G (p.Tyr375Ter)	Likely pathogenic
1120221	NM_001353108.3(CEP63):c.595del (p.Glu199fs)	Likely pathogenic
1339572	NM_178554.6(KY):c.1247T>A (p.Ile416Asn)	Likely pathogenic
1513199	NM_001353108.3(CEP63):c.1068-2A>G	Likely pathogenic

SpliceAI

2678 predictions. Top by Δscore:

Variant	Effect	Δscore
3:134495292:TCAGT:T	acceptor_loss	1.0000
3:134495293:CAGTT:C	acceptor_loss	1.0000
3:134495294:A:AG	acceptor_gain	1.0000
3:134495294:A:AT	acceptor_loss	1.0000
3:134495295:G:GA	acceptor_gain	1.0000
3:134495295:GTT:G	acceptor_gain	1.0000
3:134495361:GTGG:G	donor_gain	1.0000
3:134507105:ATAG:A	acceptor_gain	1.0000
3:134507105:ATAGG:A	acceptor_gain	1.0000
3:134507106:TA:T	acceptor_loss	1.0000
3:134507107:A:AG	acceptor_gain	1.0000
3:134507107:A:C	acceptor_loss	1.0000
3:134507107:AG:A	acceptor_gain	1.0000
3:134507107:AGG:A	acceptor_gain	1.0000
3:134507107:AGGG:A	acceptor_gain	1.0000
3:134507108:G:GG	acceptor_gain	1.0000
3:134507108:GG:G	acceptor_gain	1.0000
3:134507108:GGG:G	acceptor_gain	1.0000
3:134507108:GGGG:G	acceptor_gain	1.0000
3:134507242:GAACT:G	donor_gain	1.0000
3:134507283:GGAG:G	donor_gain	1.0000
3:134507284:G:GT	donor_gain	1.0000
3:134507284:GAG:G	donor_gain	1.0000
3:134507285:AGGT:A	donor_loss	1.0000
3:134507286:GGTAA:G	donor_loss	1.0000
3:134507287:G:GA	donor_loss	1.0000
3:134507288:T:G	donor_loss	1.0000
3:134531840:TTTA:T	acceptor_loss	1.0000
3:134531843:A:AC	acceptor_loss	1.0000
3:134531843:AGGTT:A	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014542 (3:134763549 C>A,T), RS1000016004 (3:134550714 T>C,G), RS1000018779 (3:134535120 C>T), RS1000038865 (3:134755428 T>A), RS1000046129 (3:134554632 A>G), RS1000047106 (3:134497343 C>G), RS1000055320 (3:134642182 C>T), RS1000068346 (3:134775394 C>G), RS1000082935 (3:134542142 G>C), RS1000085681 (3:134588088 T>C), RS1000096859 (3:134735570 A>G), RS1000112231 (3:134713953 C>T), RS1000125075 (3:134754282 C>A), RS1000130987 (3:134711970 T>C), RS1000138026 (3:134588248 G>A,T)

Disease associations

OMIM: gene MIM:614724 | disease phenotypes: MIM:614728, MIM:617114, MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
Seckel syndrome 6	Strong	Autosomal recessive
autosomal recessive primary microcephaly	Supportive	Autosomal recessive

Mondo (4): Seckel syndrome 6 (MONDO:0013871), myofibrillar myopathy 7 (MONDO:0014922), hereditary spastic paraplegia (MONDO:0019064), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (1): Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000444	Convex nasal ridge
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000682	Abnormal dental enamel morphology
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001511	Intrauterine growth retardation
HP:0001852	Sandal gap
HP:0002209	Sparse scalp hair
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0003577	Congenital onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0004326	Cachexia
HP:0007495	Prematurely aged appearance
HP:0009804	Tooth agenesis
HP:0010579	Cone-shaped epiphysis
HP:0011342	Mild global developmental delay
HP:0011451	Primary microcephaly
HP:0100543	Cognitive impairment

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000174_11	Height	7.000000e-08
GCST003815_90	Late-onset Alzheimer’s disease	4.000000e-06
GCST004063_33	Waist circumference adjusted for body mass index	8.000000e-07
GCST004063_38	Waist circumference adjusted for body mass index	2.000000e-11
GCST004063_42	Waist circumference adjusted for body mass index	1.000000e-06
GCST004407_3	Neurocognitive impairment in HIV-1 infection (dichotomous)	2.000000e-06
GCST004500_102	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-12
GCST004500_13	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-08
GCST004500_51	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	6.000000e-07
GCST004501_26	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	8.000000e-07
GCST004501_7	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	7.000000e-13
GCST004501_8	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	4.000000e-07
GCST004504_4	Waist circumference adjusted for BMI in non-smokers	9.000000e-07
GCST004504_5	Waist circumference adjusted for BMI in non-smokers	2.000000e-12
GCST004504_6	Waist circumference adjusted for BMI in non-smokers	2.000000e-07
GCST004562_177	Waist circumference adjusted for body mass index	9.000000e-09
GCST004562_75	Waist circumference adjusted for body mass index	4.000000e-06
GCST004562_91	Waist circumference adjusted for body mass index	1.000000e-09
GCST004563_227	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-08
GCST004563_68	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-09
GCST004563_82	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	5.000000e-06
GCST004564_123	Waist circumference adjusted for BMI in active individuals	4.000000e-09
GCST004564_124	Waist circumference adjusted for BMI in active individuals	2.000000e-06
GCST004564_125	Waist circumference adjusted for BMI in active individuals	4.000000e-10
GCST012227_1267	Hip circumference adjusted for BMI	3.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0007789	BMI-adjusted waist circumference
EFO:0007998	cognitive impairment measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	increases expression, affects expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Dexamethasone	increases expression, affects cotreatment	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Theophylline	affects cotreatment, decreases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
NCT06573866	Not specified	RECRUITING	Enhancement of Quality of Work And Life
NCT06680063	Not specified	COMPLETED	Correlation Between Clinical Assessment and Neurophysiological Assessment in Spinal Cord Injury