CEP55

Summary

CEP55 (centrosomal protein 55, HGNC:1161) is a protein-coding gene on chromosome 10q23.33, encoding Centrosomal protein of 55 kDa (Q53EZ4). Plays a role in mitotic exit and cytokinesis. It is a selective cancer dependency (DepMap: 22.9% of cell lines).

Enables identical protein binding activity. Involved in cranial skeletal system development; establishment of protein localization; and midbody abscission. Acts upstream of or within mitotic cytokinesis. Located in Flemming body and centrosome. Implicated in multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly.

Source: NCBI Gene 55165 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 139 total — 10 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 31
• Cancer dependency (DepMap): dependent in 22.9% of screened cell lines
• MANE Select transcript: NM_018131

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1161
Approved symbol	CEP55
Name	centrosomal protein 55
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10540, CT111
Ensembl gene	ENSG00000138180
Ensembl biotype	protein_coding
OMIM	610000
Entrez	55165

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371485, ENST00000445435, ENST00000496302, ENST00000897343, ENST00000912345, ENST00000912346

RefSeq mRNA: 2 — MANE Select: NM_018131 NM_001127182, NM_018131

CCDS: CCDS7428

Canonical transcript exons

ENST00000371485 — 9 exons

Exon	Start	End
ENSE00000932971	93515405	93515555
ENSE00000932972	93516935	93517248
ENSE00000932974	93519682	93519807
ENSE00001021506	93500040	93500234
ENSE00001021507	93506988	93507056
ENSE00001021508	93503113	93503388
ENSE00001422802	93496612	93496923
ENSE00001867167	93527950	93529092
ENSE00003584296	93518877	93518948

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 87.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6870 / max 975.0310, expressed in 1497 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106281	20.6723	1477
106282	1.8120	806
205946	0.2027	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	87.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.51	gold quality
secondary oocyte	CL:0000655	87.28	gold quality
sperm	CL:0000019	83.79	gold quality
ganglionic eminence	UBERON:0004023	83.63	gold quality
male germ cell	CL:0000015	81.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.25	gold quality
stromal cell of endometrium	CL:0002255	80.76	gold quality
embryo	UBERON:0000922	80.01	gold quality
rectum	UBERON:0001052	79.77	gold quality
esophagus squamous epithelium	UBERON:0006920	79.32	gold quality
testis	UBERON:0000473	78.72	gold quality
gingival epithelium	UBERON:0001949	78.51	gold quality
lower esophagus mucosa	UBERON:0035834	78.35	gold quality
mucosa of transverse colon	UBERON:0004991	78.04	gold quality
left testis	UBERON:0004533	77.53	gold quality
vermiform appendix	UBERON:0001154	77.48	gold quality
amniotic fluid	UBERON:0000173	77.31	gold quality
esophagus mucosa	UBERON:0002469	77.18	gold quality
right testis	UBERON:0004534	76.79	gold quality
gingiva	UBERON:0001828	75.27	gold quality
epithelium of esophagus	UBERON:0001976	74.97	gold quality
squamous epithelium	UBERON:0006914	74.47	gold quality
lymph node	UBERON:0000029	74.18	gold quality
caecum	UBERON:0001153	73.74	gold quality
bone marrow	UBERON:0002371	73.39	gold quality
buccal mucosa cell	CL:0002336	73.35	gold quality
mucosa of sigmoid colon	UBERON:0004993	73.14	gold quality
adrenal tissue	UBERON:0018303	73.08	gold quality
duodenum	UBERON:0002114	72.46	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	120.67
E-HCAD-13	yes	20.37
E-CURD-122	yes	16.96
E-MTAB-4850	no	255.12
E-ANND-3	no	3.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, TSG101

miRNA regulators (miRDB)

61 targeting CEP55, 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-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-3913-3P	99.74	66.53	938

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• data suggest a possible involvement of CEP55 in centrosome-dependent cellular functions, such as centrosome duplication and/or cell cycle progression, or in the regulation of cytokinesis (PMID:16406728)
• This study defines a cellular mechanism that links centralspindlin to Cep55, which, in turn, controls the midbody structure and membrane fusion at the terminal stage of cytokinesis. (PMID:16790497)
• By forming a complex with phosphatidylinositol 3’-kinase, FLJ10540 activates the PI3-kinase/AKT proto-oncogene protein pathways, providing a mechanistic basis for FLJ10540-mediated oncogenesis. (PMID:17237822)
• study shows that two proteins involved in HIV-1 budding-Tsg101, a subunit of the endosomal sorting complex required for transport I (ESCRT-I), & Alix, an ESCRT-associated protein-were recruited to the midbody during cytokinesis by interaction with Cep55 (PMID:17556548)
• that ALIX and TSG101/ESCRT-I also bind a series of proteins involved in cytokinesis, including CEP55, CD2AP, ROCK1, and IQGAP1. (PMID:17853893)
• the Cep55/Alix/ESCRT-III pathway has a role in cytokinesis and HIV-1 release (PMID:18641129)
• crystal structure of the ESCRT and ALIX-binding region (EABR) of CEP55 bound to an ALIX peptide at a resolution of 2.0 angstroms; structure shows that EABR forms an aberrant dimeric parallel coiled coil (PMID:18948538)
• FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for oral cavity squamous cell carcinoma treatment. (PMID:19525975)
• protein could be detected in breast- and lung carcinoma 9but not normal) tissues (PMID:19609239)
• Cep55 is stabilized in a phosphorylation- and Pin1-dependent manner. (PMID:19855176)
• Data provide strong evidence that CEP55 and HELLS may be used in conjunction with FOXM1 as a biomarker set for early cancer detection and indicators of malignant conversion and progression. (PMID:20400365)
• Data show that Plk1 activity negatively regulates Cep55 to ensure orderly abscission factor recruitment and ensures that this occurs only once cell contraction has completed. (PMID:21079244)
• the existence of a p53-Plk1-Cep55 axis in which p53 negatively regulates expression of Cep55, through Plk1 which, in turn, is a positive regulator of Cep55 protein stability. (PMID:22184120)
• FLJ10540 may be critical regulator of disease progression in nasopharygeal carcinoma, and the underlying mechanism may involve in the osteopontin/CD44 pathway. (PMID:22591637)
• At the midbody, BRCA2 influences the recruitment of endosomal sorting complex required for transport (ESCRT)-associated proteins, Alix and Tsg101, and formation of CEP55-Alix and CEP55-Tsg101 complexes during abscission. (PMID:22771033)
• cellular proliferation was suppressed as a result of cell cycle arrest at the G2/M phase in CEP55-knockdown cells (PMID:24390615)
• CEP55 mRNA/protein expression was observed is specific to TCC of human urinary bladder and might be used as a diagnostic biomarker and vaccine target in development of BC specific immunotherapy. (PMID:25178936)
• myotubularin-related protein 3 and myotubularin-related protein 4 may act as a bridge between CEP55 and polo-like kinase 1, ensuring proper CEP55 phosphorylation and regulating CEP55 recruitment to the midbody. (PMID:25659891)
• Which was required for FLJ10540/MMP-7 or FLJ10540/MMP-10 expressions. (PMID:25889801)
• In depth discussion of the functions of CEP55 across different effector pathways, and also its roles as a biomarker and driver of tumorigenesis, commemorating a decade of research on CEP55. [review] (PMID:25915844)
• Aberrant CEP55 expression may predict unfavorable clinical outcomes in epithelial ovarian carcinoma (EOC) patients and play an important role in regulating invasion in ovarian cancer cells. Thus, CEP55 may serve as a prognostic marker and therapeutic target for EOC (PMID:26615423)
• CEP55 plays a crucial role in promoting breast cancer cell proliferation and it might be a potential therapeutic target in breast cancer. (PMID:26902787)
• A FAK-Src signaling pathway downstream of integrin-mediated cell adhesion was found to decelerate both PLK1 degradation and CEP55 accumulation at the midbody. These data identify the regulation of PLK1 and CEP55 as steps where integrins exert control over the cytokinetic abscission. (PMID:27127172)
• CEP55 loss of function mutations likely underlie MARCH, a novel multiple congenital anomaly syndrome. (PMID:28264986)
• whole-exome sequencing lead to identification of a homozygous nonsense mutation c.256C>T (p.Arg86*) in CEP55 (centrosomal protein of 55 kDa) in autosomal recessive Meckel syndrome fetus. (PMID:28295209)
• Data suggest that USP9X as an integral component of centrosome where it functions to stabilize PCM1 and CEP55 and to promote centrosome biogenesis; N-terminal domain of USP9X appears to be responsible for physical association of USP9X with PCM1 and CEP55. (USP9X = ubiquitin-specific protease 9X; PCM1 = pericentriolar material 1 protein; CEP55 = 55kDa centrosomal protein) (PMID:28620049)
• CEP55 is a valuable prognostic factor and a potential therapeutic target in pancreatic cancer. (PMID:28724890)
• MiR-144 was down-regulated in breast cancerous tissues and cells, whereas CEP55 expression was up-regulated in breast cancerous tissues. Moreover, there existed a target relationship between miR-144 and CEP55 and negative correlation on their expressions. MiR-144 could down-regulate CEP55 expression, thereby inhibiting proliferation, invasion, migration, retarding cell cycle and accelerating cell apoptosis. (PMID:29561704)
• our data suggest that CEP55 can be used as a prognostic marker for osteosarcoma (PMID:29579156)
• iASPP associates with centrosomal protein of 55 kDa (CEP55), an important cytokinetic abscission regulator. Mechanically, iASPP acts as a PP1-targeting subunit to facilitate the interaction between PP1 and CEP55 and to remove PLK1-mediated Ser436 phosphorylation in CEP55 during late mitosis. (PMID:29743530)
• CEP55 was increased in lung cancer cells. (PMID:29750778)
• Results identified CEP55 as a potential cancer exosomal marker in head and neck squamous cell carcinoma cell lines. (PMID:30008265)
• SPAG5 interacted with centrosomal protein CEP55 to trigger the phosphorylation of AKT at Ser473. Functionally, the knockdown of CEP55 significantly attenuated SPAG5-promoted hepatocellular carcinoma (HCC) cell proliferation and migration. These data indicate that SPAG5 exhibits pro-HCC activities through interacting with CEP55. (PMID:30089483)
• Here, the authors showed that CEP55 overexpression/knockdown impacts survival of aneuploid cells. (PMID:30108112)
• A significant over expression of forkhead box protein M1 (FOXM1), polo-like kinase 1 (PLK1) and centrosomal protein 55 (CEP55) was observed in tumor samples compared to adjacent and normal bladder tissues, suggesting they may be potential candidate’s biomarkers for early diagnosis and targets for cancer therapy. (PMID:30277841)
• these results indicate that changes in EZH2 expression lead to changes in CEP55 expression in lung adenocarcinoma, and these changes are associated with its prognosis (PMID:30527357)
• CEP55 silencing remarkably suppressed proliferation and induced apoptosis of castration-resistant prostate cells, indicating that miR-144-3p affects cell survival and proliferation by downregulating CEP55 (PMID:30536308)
• we emphasize the recent work from our laboratory, which highlights the functional role of CEP55 in protecting aneuploid cells from death. We also discuss the rationale of targeting CEP55 in vivo, which could prove to be a novel and effective therapeutic strategy for sensitizing cells to microtubule inhibitors and might offer significantly improved patient outcome (PMID:30601084)
• CEP55 overexpression is associated with epithelial-mesenchymal transition in renal cell carcinoma. (PMID:30607788)
• considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development (PMID:30622327)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep55l	ENSDARG00000102349
mus_musculus	Cep55	ENSMUSG00000024989
rattus_norvegicus	Cep55	ENSRNOG00000016377

Protein

Protein identifiers

Centrosomal protein of 55 kDa — Q53EZ4 (reviewed: Q53EZ4)

Alternative names: Up-regulated in colon cancer 6

All UniProt accessions (2): Q53EZ4, H0Y432

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in mitotic exit and cytokinesis. Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis. Not required for microtubule nucleation. Plays a role in the development of the brain and kidney.

Subunit / interactions. Homodimer. Interacts (phosphorylated on Ser-425 and Ser-428) with PLK1; the interaction is indirect via the MTMR3:MTMR4 heterooligomer, occurs during early mitosis, regulates the phosphorylation of CEP55 by PLK1 and its recruitment to the midbody where it can mediate cell abscission. Interacts with AKAP9/CG-NAP; the interaction occurs in interphase and is lost upon mitotic entry. Interacts with PCNT/Kendrin; the interaction occurs in interphase and is lost upon mitotic entry. Directly interacts with PDCD6IP; this interaction is required for PDCD6IP targeting to the midbody; CEP55 binds PDCD6IP in a 2:1 stoichiometry; PDCD6IP competes with TSG101 for the same binding site. Interacts with TSG101; TSG101 competes with PDCD6IP for the same binding site; interaction is required for cytokinesis but not for viral budding. Interacts with MVB12A, VPS37B, VPS37C and VPS28.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cleavage furrow. Midbody. Midbody ring.

Tissue specificity. Expressed in embryonic brain. Expressed in fetal brain ganglionic eminence, kidney tubules and multinucleate neurons in the temporal cortex. Expressed in adult brain, cerebellum, kidney tubules, intestine and muscles (at protein level). Widely expressed, mostly in proliferative tissues. Highly expressed in testis. Intermediate levels in adult and fetal thymus, as well as in various cancer cell lines. Low levels in different parts of the digestive tract, bone marrow, lymph nodes, placenta, fetal heart and fetal spleen. Hardly detected in brain.

Post-translational modifications. There is a hierachy of phosphorylation, where both Ser-425 and Ser-428 are phosphorylated at the onset of mitosis, prior to Ser-436. Phosphorylation at Ser-425 and Ser-428 is required for dissociation from the centrosome at the G2/M boundary. Phosphorylation at the 3 sites, Ser-425, Ser-428 and Ser-436, is required for protein function at the final stages of cell division to complete cytokinesis successfully.

Disease relevance. Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH) [MIM:236500] An autosomal recessive, congenital disease characterized by severe hydranencephaly with multinucleated neurons, renal aplasia or dysplasia, and hypoplastic kidneys. Hydranencephaly is an anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. MARCH results in death in utero or in the perinatal period. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53EZ4-1	1	yes
Q53EZ4-2	2

RefSeq proteins (2): NP_001120654, NP_060601* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022008	EABR	Domain
IPR038926	CEP55	Family

Pfam: PF12180

UniProt features (37 total): mutagenesis site 9, sequence variant 6, modified residue 5, sequence conflict 5, region of interest 4, coiled-coil region 3, splice variant 2, chain 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3E1R	X-RAY DIFFRACTION	2
3WUT	X-RAY DIFFRACTION	2.3
3WUV	X-RAY DIFFRACTION	2.79
3WUU	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53EZ4-F1	82.85	0.58

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 (5): 425, 428, 430, 436, 96

Mutagenesis-validated functional residues (9):

Position	Phenotype
184	abolishes interaction with pdcd6ip.
187	abolishes interaction with pdcd6ip.
188	diminishes interaction with pdcd6ip.
191	abolishes interaction with pdcd6ip.
192	abolishes interaction with pdcd6ip.
396	no effect on phosphorylation in mitotic cells.
425	partial loss of phosphorylation in mitotic cells. complete loss of phosphorylation in mitotic cells; when associated wit
428	partial loss of phosphorylation in mitotic cells. complete loss of phosphorylation in mitotic cells; when associated wit
436	no effect on phosphorylation in mitotic cells. arrests mitotic cells at the midbody stage; when associated with a-425 an

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 369 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_CHROMOSOME_LOCALIZATION, MONTERO_THYROID_CANCER_POOR_SURVIVAL_UP, GOBP_CYTOKINETIC_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, GOBP_ORGANELLE_FISSION, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, GOBP_CYTOKINESIS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, FISCHER_G2_M_CELL_CYCLE

GO Biological Process (6): mitotic cytokinesis (GO:0000281), establishment of protein localization (GO:0045184), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), midbody abscission (GO:0061952), cranial skeletal system development (GO:1904888), cell division (GO:0051301)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), membrane (GO:0016020), midbody (GO:0030496), cleavage furrow (GO:0032154), intercellular bridge (GO:0045171), Flemming body (GO:0090543), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
microtubule organizing center	2
intracellular membraneless organelle	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
establishment of localization	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of intracellular signal transduction	1
membrane organization	1
mitotic cytokinetic process	1
anatomical structure development	1
cellular process	1
protein binding	1
binding	1
intracellular anatomical structure	1
centriole	1
cell division site	1
plasma membrane region	1
midbody	1

Protein interactions and networks

STRING

1736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP55	TSG101	Q99816	998
CEP55	PDCD6IP	Q8WUM4	924
CEP55	CHMP4A	Q9BY43	846
CEP55	KIF23	Q02241	820
CEP55	RACGAP1	Q9H0H5	804
CEP55	CHMP4C	Q96CF2	800
CEP55	PDCD6	O75340	792
CEP55	VPS28	Q9UK41	785
CEP55	KIF20A	O95235	783
CEP55	CDK1	P06493	759
CEP55	DLGAP5	Q15398	755
CEP55	CNTLN	Q9NXG0	754
CEP55	MELK	Q14680	751
CEP55	KIF4A	O95239	748
CEP55	CENPF	P49454	745

IntAct

510 interactions, top by confidence:

A	B	Type	Score
CEP55	TSG101	psi-mi:“MI:0915”(physical association)	0.970
TSG101	CEP55	psi-mi:“MI:0915”(physical association)	0.970
PDCD6IP	CEP55	psi-mi:“MI:0915”(physical association)	0.960
ARHGEF15	CEP55	psi-mi:“MI:0915”(physical association)	0.810
CEP55	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.810
CEP55	VPS37C	psi-mi:“MI:0915”(physical association)	0.800
VPS37C	CEP55	psi-mi:“MI:0915”(physical association)	0.800
CEP55	CDC45	psi-mi:“MI:0915”(physical association)	0.780
CEP55	PLEKHG6	psi-mi:“MI:0915”(physical association)	0.780
CEP55	RBM17	psi-mi:“MI:0915”(physical association)	0.780
WASHC3	CEP55	psi-mi:“MI:0915”(physical association)	0.780
CDC45	CEP55	psi-mi:“MI:0915”(physical association)	0.780
CEP55	WASHC3	psi-mi:“MI:0915”(physical association)	0.780
SDCBP	CEP55	psi-mi:“MI:0915”(physical association)	0.720
CEP55	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
CEP55	TCL1A	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (416): CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid), CEP55 (Two-hybrid)

ESM2 similar proteins: A0MZ66, A0MZ67, A6PWD2, A7MD70, B3DLE8, B9EKI3, F7DP49, O35550, O35551, O45420, P82094, Q05D60, Q08DR9, Q15276, Q28IH8, Q3KR99, Q3UIJ9, Q4L180, Q4R7H3, Q4V7C8, Q53EZ4, Q5BIX7, Q5R923, Q5RA03, Q5RI56, Q5U3Z6, Q6NRC9, Q6NRW2, Q6P0R8, Q6P402, Q6P6L0, Q7YS99, Q7Z7B0, Q861Q8, Q8BT07, Q8BVC4, Q8K2Q9, Q8K3K8, Q8K4T4, Q8R5M4

Diamond homologs: Q4V7C8, Q502I3, Q53EZ4, Q8BT07

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDK1	down-regulates	CEP55	phosphorylation
MAPK1	down-regulates	CEP55	phosphorylation
PLK1	up-regulates	CEP55	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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×	1e-07
Loss of proteins required for interphase microtubule organization from the centrosome	8	24.4×	1e-07
Anchoring of the basal body to the plasma membrane	11	23.9×	2e-10
AURKA Activation by TPX2	8	23.4×	1e-07
Recruitment of mitotic centrosome proteins and complexes	8	20.9×	3e-07
Regulation of PLK1 Activity at G2/M Transition	8	19.5×	4e-07
Recruitment of NuMA to mitotic centrosomes	8	17.9×	6e-07

GO biological processes:

GO term	Partners	Fold	FDR
centrosome cycle	5	22.8×	4e-04
cilium assembly	11	10.9×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	2
Uncertain significance	72
Likely benign	21
Benign	17

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1175779	NM_018131.5(CEP55):c.307C>T (p.Gln103Ter)	Pathogenic
2041378	NM_018131.5(CEP55):c.908del (p.Lys303fs)	Pathogenic
2989041	NM_018131.5(CEP55):c.1069C>T (p.Gln357Ter)	Pathogenic
393995	GRCh37/hg19 10p15.3-q26.3(chr10:93297-135378918)x3	Pathogenic
437874	NM_018131.5(CEP55):c.1274C>A (p.Ser425Ter)	Pathogenic
437875	NM_018131.5(CEP55):c.256C>T (p.Arg86Ter)	Pathogenic
520544	NM_018131.5(CEP55):c.1191+2T>C	Pathogenic
562113	NM_018131.5(CEP55):c.514dup (p.Ile172fs)	Pathogenic
833253	NC_000010.11:g.(?93161309)(93797823_?)del	Pathogenic
982559	NM_018131.5(CEP55):c.993+3A>C	Pathogenic
1180716	NM_018131.5(CEP55):c.1147G>T (p.Glu383Ter)	Likely pathogenic
3065688	NM_018131.5(CEP55):c.547C>T (p.Gln183Ter)	Likely pathogenic

SpliceAI

1355 predictions. Top by Δscore:

Variant	Effect	Δscore
10:93500036:ACAG:A	acceptor_loss	1.0000
10:93500037:CA:C	acceptor_loss	1.0000
10:93500038:A:AG	acceptor_gain	1.0000
10:93500038:A:AT	acceptor_loss	1.0000
10:93500039:G:GG	acceptor_gain	1.0000
10:93500039:GACC:G	acceptor_gain	1.0000
10:93507054:GAT:G	donor_gain	1.0000
10:93515391:A:AG	acceptor_gain	1.0000
10:93515392:T:G	acceptor_gain	1.0000
10:93515400:TTAA:T	acceptor_loss	1.0000
10:93515402:AAG:A	acceptor_gain	1.0000
10:93515403:A:G	acceptor_gain	1.0000
10:93515552:GAAG:G	donor_gain	1.0000
10:93515553:AAG:A	donor_loss	1.0000
10:93515554:AG:A	donor_loss	1.0000
10:93515556:G:GC	donor_loss	1.0000
10:93518872:TACAG:T	acceptor_loss	1.0000
10:93518874:CAGGT:C	acceptor_loss	1.0000
10:93518875:AGG:A	acceptor_loss	1.0000
10:93518944:AACAG:A	donor_loss	1.0000
10:93518945:ACAG:A	donor_loss	1.0000
10:93518946:CAG:C	donor_loss	1.0000
10:93518947:AG:A	donor_loss	1.0000
10:93518948:GG:G	donor_loss	1.0000
10:93518949:GT:G	donor_loss	1.0000
10:93518950:T:A	donor_loss	1.0000
10:93496700:G:T	donor_gain	0.9900
10:93500039:GA:G	acceptor_gain	0.9900
10:93500039:GAC:G	acceptor_gain	0.9900
10:93503305:G:GT	donor_gain	0.9900

AlphaMissense

3035 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:93515448:G:C	R191P	0.995
10:93515426:T:A	W184R	0.994
10:93515426:T:C	W184R	0.994
10:93515428:G:C	W184C	0.991
10:93515428:G:T	W184C	0.991
10:93528076:T:C	C440R	0.991
10:93528122:T:C	L455P	0.988
10:93528085:T:A	C443S	0.986
10:93528086:G:C	C443S	0.986
10:93515405:G:C	A177P	0.984
10:93528076:T:A	C440S	0.981
10:93528077:G:C	C440S	0.981
10:93515469:T:C	L198P	0.980
10:93515430:T:C	L185P	0.979
10:93528085:T:C	C443R	0.979
10:93507049:T:C	L174P	0.978
10:93519767:T:C	L384P	0.978
10:93528097:T:G	Y447D	0.978
10:93528132:T:A	H458Q	0.978
10:93528132:T:G	H458Q	0.978
10:93515427:G:C	W184S	0.977
10:93528142:T:A	C462S	0.977
10:93528143:G:C	C462S	0.977
10:93528122:T:A	L455Q	0.976
10:93515409:T:C	L178P	0.975
10:93528142:T:C	C462R	0.975
10:93528144:T:G	C462W	0.974
10:93515415:A:T	K180I	0.970
10:93515445:A:C	Q190P	0.970
10:93515416:A:C	K180N	0.966

dbSNP variants (sampled 300 via entrez): RS1000086958 (10:93508634 A>G,T), RS1000112075 (10:93496760 T>C,G), RS1000348341 (10:93514778 T>C), RS1000367265 (10:93521305 G>A,T), RS1000410282 (10:93502231 T>G), RS1000420645 (10:93527494 A>G), RS1000437556 (10:93520673 G>C), RS1000491195 (10:93520350 C>G,T), RS1000751701 (10:93529120 G>T), RS1000769070 (10:93519369 G>A), RS1000830152 (10:93496055 G>A,C), RS1000903500 (10:93495871 T>C), RS1001176862 (10:93509860 CA>C), RS1001206219 (10:93509476 T>G), RS1001307997 (10:93508936 A>G)

Disease associations

OMIM: gene MIM:610000 | disease phenotypes: MIM:236500, MIM:614388, MIM:600512

GenCC curated gene-disease

Disease	Classification	Inheritance
multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome	Strong	Autosomal recessive
complex neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (5): multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (MONDO:0009359), encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (MONDO:0013726), autosomal dominant epilepsy with auditory features (MONDO:0010898), epilepsy, familial temporal lobe, 1 (MONDO:0700090), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (3): Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (Orphanet:500135), DNM1L-related encephalopathy due to mitochondrial and peroxisomal fission defect (Orphanet:330050), Epilepsy with auditory features (Orphanet:101046)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000089	Renal hypoplasia
HP:0000107	Renal cyst
HP:0000110	Renal dysplasia
HP:0000308	Microretrognathia
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000418	Narrow nasal ridge
HP:0000452	Choanal stenosis
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000476	Cystic hygroma
HP:0000954	Single transverse palmar crease
HP:0001156	Brachydactyly
HP:0001321	Cerebellar hypoplasia
HP:0001562	Oligohydramnios
HP:0001762	Talipes equinovarus
HP:0002009	Potter facies
HP:0002089	Pulmonary hypoplasia
HP:0002324	Hydranencephaly
HP:0002365	Hypoplasia of the brainstem
HP:0002804	Arthrogryposis multiplex congenita
HP:0003811	Neonatal death
HP:0003826	Stillbirth
HP:0004209	Clinodactyly of the 5th finger
HP:0004691	2-3 toe syndactyly
HP:0005989	Redundant neck skin
HP:0012300	Ureteral agenesis
HP:0012725	Cutaneous syndactyly
HP:0045025	Narrow palpebral fissure

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007202_19	High density lipoprotein cholesterol levels	7.000000e-06
GCST009391_1252	Metabolite levels	9.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004761	uric acid measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537297	Autosomal Dominant Lateral Temporal Lobe Epilepsy (supp.)
C565507	Hydranencephaly with Renal Aplasia-Dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	3
sodium arsenite	increases expression	2
Progesterone	decreases expression, increases expression	2
Quercetin	affects phosphorylation, increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Tretinoin	decreases expression	2
Tunicamycin	decreases expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
sulforaphane	increases expression	1
boron nitride	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	decreases acetylation, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
deguelin	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D6P8	IPi002-A	Induced pluripotent stem cell	Male
CVCL_D6P9	IPi002-B	Induced pluripotent stem cell	Male
CVCL_D6PA	IPi002-C	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder