CENPF

Summary

CENPF (centromere protein F, HGNC:1857) is a protein-coding gene on chromosome 1q41, encoding Centromere protein F (P49454). Required for kinetochore function and chromosome segregation in mitosis. It is a selective cancer dependency (DepMap: 11.8% of cell lines).

This gene encodes a protein that associates with the centromere-kinetochore complex. The protein is a component of the nuclear matrix during the G2 phase of interphase. In late G2 the protein associates with the kinetochore and maintains this association through early anaphase. It localizes to the spindle midzone and the intracellular bridge in late anaphase and telophase, respectively, and is thought to be subsequently degraded. The localization of this protein suggests that it may play a role in chromosome segregation during mitotis. It is thought to form either a homodimer or heterodimer. Autoantibodies against this protein have been found in patients with cancer or graft versus host disease.

Source: NCBI Gene 1063 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Stromme syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 951 total — 24 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 33
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• MANE Select transcript: NM_016343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1857
Approved symbol	CENPF
Name	centromere protein F
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	hcp-1
Ensembl gene	ENSG00000117724
Ensembl biotype	protein_coding
OMIM	600236
Entrez	1063

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000366955, ENST00000464322, ENST00000467765, ENST00000469862, ENST00000495259, ENST00000706764, ENST00000706765, ENST00000706766, ENST00000934982, ENST00000934983, ENST00000934984

RefSeq mRNA: 1 — MANE Select: NM_016343 NM_016343

CCDS: CCDS31023

Canonical transcript exons

ENST00000366955 — 20 exons

Exon	Start	End
ENSE00001443108	214663591	214664571
ENSE00003523917	214648675	214648827
ENSE00003583081	214651710	214651886
ENSE00003638180	214652828	214652989
ENSE00003996890	214655241	214655403
ENSE00003996891	214630534	214630662
ENSE00003996894	214603195	214603321
ENSE00003996895	214613714	214613916
ENSE00003996896	214658850	214659028
ENSE00003996898	214644557	214647400
ENSE00003996899	214637866	214638001
ENSE00003996900	214629046	214629171
ENSE00003996901	214632480	214632602
ENSE00003996904	214614832	214615028
ENSE00003996906	214656933	214657409
ENSE00003996908	214618573	214618694
ENSE00003996912	214619129	214619220
ENSE00003996913	214622079	214622281
ENSE00003996914	214620655	214620946
ENSE00003996916	214639921	214643324

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.2172 / max 1213.6846, expressed in 1481 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8534	15.6811	1340
8535	12.6554	1138
8536	2.2953	702
8540	0.3213	167
8539	0.2641	125

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.52	gold quality
ganglionic eminence	UBERON:0004023	98.78	gold quality
embryo	UBERON:0000922	97.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.07	gold quality
trabecular bone tissue	UBERON:0002483	93.26	gold quality
stromal cell of endometrium	CL:0002255	89.94	gold quality
bone marrow	UBERON:0002371	88.97	gold quality
bone marrow cell	CL:0002092	87.47	gold quality
mucosa of transverse colon	UBERON:0004991	87.40	gold quality
left testis	UBERON:0004533	87.21	gold quality
right testis	UBERON:0004534	86.70	gold quality
testis	UBERON:0000473	86.68	gold quality
gingival epithelium	UBERON:0001949	85.63	silver quality
tongue squamous epithelium	UBERON:0006919	84.88	silver quality
esophagus mucosa	UBERON:0002469	84.46	gold quality
adrenal tissue	UBERON:0018303	84.23	gold quality
oral cavity	UBERON:0000167	84.07	gold quality
lower esophagus mucosa	UBERON:0035834	84.04	gold quality
thymus	UBERON:0002370	82.28	gold quality
gingiva	UBERON:0001828	82.23	gold quality
rectum	UBERON:0001052	81.55	gold quality
epithelium of nasopharynx	UBERON:0001951	81.45	silver quality
cortical plate	UBERON:0005343	80.67	gold quality
endometrium	UBERON:0001295	80.18	gold quality
colonic epithelium	UBERON:0000397	79.98	gold quality
hair follicle	UBERON:0002073	79.64	gold quality
buccal mucosa cell	CL:0002336	79.50	silver quality
cartilage tissue	UBERON:0002418	78.97	gold quality
amniotic fluid	UBERON:0000173	77.16	gold quality

Single-cell (SCXA)

Detected in 38 experiment(s), a significant marker in 35.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	3538.73
E-HCAD-56	yes	3231.11
E-CURD-112	yes	3129.25
E-MTAB-8894	yes	3082.39
E-MTAB-10485	yes	2538.70
E-HCAD-5	yes	2306.34
E-MTAB-9435	yes	1911.39
E-GEOD-124472	yes	1686.22
E-CURD-79	yes	1652.50
E-MTAB-8559	yes	1421.94
E-MTAB-10662	yes	1392.76
E-ENAD-20	yes	1379.99
E-MTAB-10290	yes	1377.88
E-MTAB-10018	yes	1225.66
E-HCAD-10	yes	1225.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXM1

miRNA regulators (miRDB)

53 targeting CENPF, 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-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-3125	99.14	68.49	2269

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Data suggest that farnesylation of Cenp-F is required not only for its localisation to the nuclear envelope and kinetochores but also for timely progression through G2/M and its degradation after mitosis. (PMID:12154071)
• Data show that mitosin associates preferentially with kinetochores of unaligned chromosomes. (PMID:12974617)
• CENP-F expression presents a theoretical advantage for the analysis of the precise cell cycle of G2 to M cells, compared to Ki-67. (PMID:14720137)
• Results suggest that mitosin is a negative regulator of ATF4 in interphase through direct interaction. (PMID:15677469)
• Mitosin is therefore essential for full chromosome alignment, possibly by promoting proper kinetochore attachments through modulating CENP-E and dynein functions (PMID:15870278)
• In addition to regulating kinetochore-microtubule interactions, Cenp-F might be required to protect centromeric cohesion prior to anaphase commitment. (PMID:16219694)
• Data show that the absence of nuclear CENP-F does not affect cell cycle progression in S and G2, and that CENP-F is crucial for efficient assembly of a stable microtubule-kinetochore interface. (PMID:16252009)
• REVIEW: involvement in mitotic control, microtubule dynamics, transcriptional regulation, and muscle cell differentiation. (PMID:16456711)
• CENP-F is a novel microtubule-binding protein that possesses two microtubule-binding domains at opposite ends of the molecule. The C-terminal microtubule-binding domain was found to stimulate microtubule polymerization in vitro. (PMID:16601978)
• CENP-F upregulation was significantly associated breast cancer (PMID:17205517)
• Ndel1, Nde1, and Lis1 localize to kinetochores in a Cenp-F-dependent manner. (PMID:17600710)
• high expression levels of the CENP-F appeared to be the molecular background of higher proliferative activity, and they were correlated with high SUV (standardized uptake value) in breast cancer (PMID:19102762)
• Study analyzed the distribution of PARP-1 and its interaction with CENP-B, -E, and -F during mitosis and apoptosis. (PMID:19723035)
• Data identified Cenp-F as a potential new molecular target for NBPs in tumour cells. (PMID:20015195)
• Data show that the post-anaphase, KEN-box-dependent degradation of Cenp-F requires it to be farnesylated, a post-translational modification usually linked to membrane association. (PMID:20053638)
• These results uncover a novel role of CENP-F in regulation of epigenetic modification on histone H3. (PMID:20213041)
• Mitosin did not predict patient survival in this series of cutaneous melanomas. (PMID:20398247)
• the interaction between LANA and the kinetochore proteins CENP-F and Bub1 is important for KSHV genome tethering and its segregation to new daughter cells (PMID:20660191)
• Data suggest that CENP-F protein is a valuable marker of nasopharyngeal carcinoma progression, and CENP-F expression is associated with poor overall survival of patients. (PMID:20828406)
• Cenp-F plays a role in organization of interphase chromatin through association and possibly regulation of DNA-PK. (PMID:20978035)
• Centromere protein F and survivin are malignant behaviour markers for colorectal gastrointestinal stromal tumours. (PMID:21613637)
• Rab5 forms a complex with a subset of CENP-F in mitotic cells and regulates the kinetics of release of CENP-F from the nuclear envelope and its accumulation on kinetochores. (PMID:21987812)
• Coincidently amplified CDK13, GMNN, and CENPF genes can play a role as common cancer-driver genes in human cancers. (PMID:22912832)
• Data suggest that ASUN promotes perinuclear enrichment of dynein at G2/M that facilitates BICD2- and CENP-F-mediated anchoring of dynein to nuclear pore complexes. (PMID:23097494)
• CENP-F may serve as valuable molecular marker for predicting prognosis of ESCC patients. data indicate potential benefit of combining ZOL with cisplatin in ESCC; CENP-F expressionmay have therapeutic implications. (PMID:23163484)
• data suggest that CENPF is frequently overexpressed in HCC and plays a critical role in driving HCC tumorigenesis (PMID:23791740)
• FOXM1 and CENPF function synergistically to promote tumor growth by coordinated regulation of target gene expression and activation of key signaling pathways associated with prostate cancer malignancy. (PMID:24823640)
• Our data identify CENPF as a new centriolar disease gene implicated in severe human ciliopathy and microcephaly related phenotypes (PMID:25564561)
• the increased expression of CENPF plays an important role in the progression of PCa. (PMID:25647485)
• N-terminal microtubule-binding domain of CENP-F prefers curled oligomers of tubulin relative to microtubule walls by approximately fivefold, suggesting it may contribute to the firm bonds between kinetochores and flared plus ends of dynamic microtubules (PMID:26101217)
• Mitosin and pHH3 immunostaining predict poorer survival in astrocytomas WHO grades II and III. (PMID:26188054)
• Miro and Cenp-F promote anterograde mitochondrial movement and proper mitochondrial distribution in daughter cells. (PMID:26259702)
• We show for the first time that Stromme syndrome is an autosomal-recessive disease caused by mutations in CENPF that can result in a wide phenotypic spectrum. (PMID:26820108)
• Tumors with higher topoisomerase IIalpha and/or mitosin expression have a higher risk of recurrence after initial treatment, and these patients may benefit from adjuvant treatment and closer radiological follow-up (PMID:28301542)
• This is the second case report identifying CENPF mutation as the cause of Stromme syndrome (PMID:28407396)
• Authors suggest that CENP-F might act as a transporter of mitochondria and other cellular cargoes by attaching them to dynamic microtubule ends during both polymerization and depolymerization of tubulin. (PMID:28701340)
• a point mutation within an adjacent leucine zipper affecting the kinetochore targeting of Cenp-F KT-core domain impairs its interaction with Bub1, but not with Nup133 (PMID:29632243)
• CENP-E and CENP-F directly and specifically interact with distinct BUB mitotic checkpoint Ser/Thr kinases (PMID:29748388)
• Data demonstrate a direct association between rs7289, a CENP-F single nucleotide polymorphism and heart failure patients with reduced ejection fraction. (PMID:29765066)
• The results establish CENP-F as the first well-characterized Nde1 cargo protein, and reveal phosphorylation control of Nde1 cargo binding throughout a substantial fraction of the cell cycle. (PMID:29930206)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cenpf	ENSDARG00000055133
danio_rerio	si:dkeyp-115e12.6	ENSDARG00000090986
mus_musculus	Cenpf	ENSMUSG00000026605
rattus_norvegicus	Cenpf	ENSRNOG00000003388

Protein

Protein identifiers

Centromere protein F — P49454 (reviewed: P49454)

Alternative names: AH antigen, Kinetochore protein CENPF, Mitosin

All UniProt accessions (2): A0A9L9PXU7, P49454

UniProt curated annotations — full annotation on UniProt →

Function. Required for kinetochore function and chromosome segregation in mitosis. Required for kinetochore localization of dynein, LIS1, NDE1 and NDEL1. Regulates recycling of the plasma membrane by acting as a link between recycling vesicles and the microtubule network though its association with STX4 and SNAP25. Acts as a potential inhibitor of pocket protein-mediated cellular processes during development by regulating the activity of RB proteins during cell division and proliferation. May play a regulatory or permissive role in the normal embryonic cardiomyocyte cell cycle and in promoting continued mitosis in transformed, abnormally dividing neonatal cardiomyocytes. Interaction with RB directs embryonic stem cells toward a cardiac lineage. Involved in the regulation of DNA synthesis and hence cell cycle progression, via its C-terminus. Has a potential role regulating skeletal myogenesis and in cell differentiation in embryogenesis. Involved in dendritic cell regulation of T-cell immunity against chlamydia.

Subunit / interactions. Interacts with and STX4 (via C-terminus). Interacts (via N-terminus) with RBL1, RBL2 and SNAP25. Self-associates. Interacts with CENP-E and BUBR1 (via C-terminus). Interacts (via C-terminus) with NDE1, NDEL1 and RB1.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus matrix. Chromosome. Centromere. Kinetochore. Cytoskeleton. Spindle.

Post-translational modifications. Hyperphosphorylated during mitosis.

Disease relevance. Stromme syndrome (STROMS) [MIM:243605] An autosomal recessive congenital disorder characterized by intestinal atresia, ocular anomalies, microcephaly, and renal and cardiac abnormalities in some patients. The disease has features of a ciliopathy, and lethality in early childhood is observed in severe cases. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the centromere protein F family.

RefSeq proteins (1): NP_057427* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018302	CenpF/LEK1_Rb-prot-bd	Domain
IPR018463	Centromere_CenpF_N	Domain
IPR019513	Centromere_CenpF_leu-rich_rpt	Domain
IPR043513	Cenp-F	Family

Pfam: PF10473, PF10481, PF10490

UniProt features (93 total): modified residue 39, sequence variant 14, region of interest 11, sequence conflict 11, coiled-coil region 7, compositionally biased region 5, repeat 2, chain 1, propeptide 1, short sequence motif 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for P49454 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (40): 106, 144, 151, 154, 158, 242, 276, 773, 783, 821, 834, 838, 876, 1248, 1255, 1259, 1651, 1652, 1654, 1726 …

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-156711	Polo-like kinase mediated events
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 578 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MYAATNNNNNNNGGC_UNKNOWN, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GNF2_CENPF, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SEMBA_FHIT_TARGETS_DN, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, MORF_RRM1, GNF2_H2AFX, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN

GO Biological Process (16): mitotic cell cycle (GO:0000278), kidney development (GO:0001822), chromosome segregation (GO:0007059), mitotic spindle assembly checkpoint signaling (GO:0007094), muscle organ development (GO:0007517), response to xenobiotic stimulus (GO:0009410), regulation of G2/M transition of mitotic cell cycle (GO:0010389), protein transport (GO:0015031), regulation of striated muscle tissue development (GO:0016202), ventricular system development (GO:0021591), cell differentiation (GO:0030154), negative regulation of DNA-templated transcription (GO:0045892), cell division (GO:0051301), metaphase chromosome alignment (GO:0051310), kinetochore assembly (GO:0051382), DNA biosynthetic process (GO:0071897)

GO Molecular Function (7): chromatin binding (GO:0003682), microtubule binding (GO:0008017), protein homodimerization activity (GO:0042803), dynein complex binding (GO:0070840), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), transcription factor binding (GO:0008134)

GO Cellular Component (21): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), chromatin (GO:0000785), spindle pole (GO:0000922), outer kinetochore (GO:0000940), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), axoneme (GO:0005930), nuclear matrix (GO:0016363), midbody (GO:0030496), ciliary basal body (GO:0036064), pronucleus (GO:0045120), perinuclear region of cytoplasm (GO:0048471), ciliary transition fiber (GO:0097539), chromosome (GO:0005694), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle, Mitotic	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
G2/M Transition	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Mitotic G2-G2/M phases	1
Cell Cycle Checkpoints	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	9
intracellular membraneless organelle	3
animal organ development	2
binding	2
nucleus	2
nuclear lumen	2
microtubule organizing center	2
cytoplasm	2
cilium	2
cell cycle	1
mitotic nuclear division	1
renal system development	1
cell cycle process	1
mitotic cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
muscle structure development	1
response to chemical	1
G2/M transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
striated muscle tissue development	1
regulation of muscle organ development	1
regulation of muscle tissue development	1
brain development	1
system development	1
cellular developmental process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cellular process	1
chromosome localization	1
nuclear chromosome segregation	1
kinetochore organization	1
protein-containing complex assembly	1
membraneless organelle assembly	1

Protein interactions and networks

STRING

2610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CENPF	CENPE	Q02224	987
CENPF	BUB1B	O60566	919
CENPF	KIF2C	Q99661	907
CENPF	BUB1	O43683	904
CENPF	CENPA	P49450	903
CENPF	ZWINT	O95229	877
CENPF	CENPI	Q92674	864
CENPF	FOXM1	Q08050	845
CENPF	AURKB	Q96GD4	839
CENPF	BIRC5	O15392	826
CENPF	CENPS	Q8N2Z9	812
CENPF	CENPB	P07199	810
CENPF	TOP2A	P11388	804
CENPF	NUP133	Q8WUM0	803
CENPF	CDC20	Q12834	802
CENPF	ASPM	Q8IZT6	802

IntAct

104 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
CENPF	NDEL1	psi-mi:“MI:0915”(physical association)	0.750
NDEL1	CENPF	psi-mi:“MI:0915”(physical association)	0.750
NDEL1	CENPF	psi-mi:“MI:0403”(colocalization)	0.750
GPC6	GPC4	psi-mi:“MI:0914”(association)	0.710
CCDC68	NDC80	psi-mi:“MI:0914”(association)	0.640
G3BP1	COX5A	psi-mi:“MI:0914”(association)	0.530
FNTB	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RNF166	MPDZ	psi-mi:“MI:0914”(association)	0.530
COG6	EXOC5	psi-mi:“MI:0914”(association)	0.530
WASF3	HOXB9	psi-mi:“MI:0914”(association)	0.530
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
PPP1R13B	CCDC85C	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
MTMR9	CENPF	psi-mi:“MI:0914”(association)	0.530
FNTB	CAPN1	psi-mi:“MI:0914”(association)	0.530
MAD2L1BP	KIF20A	psi-mi:“MI:0914”(association)	0.530
NHLH2	AP3B1	psi-mi:“MI:0914”(association)	0.530
LRRK2	DFFA	psi-mi:“MI:0914”(association)	0.530
ATR	CENPF	psi-mi:“MI:0915”(physical association)	0.500
CENPF	ATRIP	psi-mi:“MI:0915”(physical association)	0.500
NUP133	CENPF	psi-mi:“MI:0915”(physical association)	0.480
CENPF	ERP29	psi-mi:“MI:0915”(physical association)	0.400
SETD2	CENPF	psi-mi:“MI:0915”(physical association)	0.400
CENPF	H1-1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (162): CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPF (Affinity Capture-MS)

ESM2 similar proteins: D3ZZL9, E9Q1U1, F4I9A2, O75330, O97961, P49454, P61430, P97779, Q00547, Q03410, Q0VBY1, Q13439, Q14789, Q15075, Q15643, Q28628, Q4R7H3, Q53EZ4, Q5M7B7, Q5RI56, Q5T9S5, Q60563, Q61595, Q62209, Q640L5, Q6TFL3, Q70FJ1, Q7FAD5, Q861Q8, Q86UP2, Q8BL66, Q8CDI7, Q8CHG3, Q8HYY4, Q8IWJ2, Q8NB25, Q8NCX0, Q8R5M4, Q90631, Q90Z16

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SPAG5	“up-regulates activity”	CENPF

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 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
Centrosome maturation	5	14.1×	7e-04
Amplification of signal from the kinetochores	6	13.1×	2e-04
Mitotic Spindle Checkpoint	7	12.3×	1e-04
AURKA Activation by TPX2	7	11.8×	1e-04
Recruitment of mitotic centrosome proteins and complexes	7	10.6×	2e-04
Loss of Nlp from mitotic centrosomes	6	10.6×	6e-04
Loss of proteins required for interphase microtubule organization from the centrosome	6	10.6×	6e-04
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	8	10.4×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment of mitotic spindle orientation	5	20.6×	2e-03
chromosome segregation	10	14.8×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	33
Uncertain significance	533
Likely benign	171
Benign	96

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029441	NM_016343.4(CENPF):c.1323+1G>A	Pathogenic
1452892	NM_016343.4(CENPF):c.532C>T (p.Arg178Ter)	Pathogenic
1456827	NM_016343.4(CENPF):c.5136del (p.Gly1713fs)	Pathogenic
1458196	NM_016343.4(CENPF):c.1222C>T (p.Gln408Ter)	Pathogenic
1700193	NM_016343.4(CENPF):c.8786C>G (p.Ser2929Ter)	Pathogenic
190385	NM_016343.4(CENPF):c.1744G>T (p.Glu582Ter)	Pathogenic
190386	NM_016343.4(CENPF):c.574-2A>C	Pathogenic
190387	NM_016343.4(CENPF):c.8692C>T (p.Arg2898Ter)	Pathogenic
2034456	NM_016343.4(CENPF):c.7900G>T (p.Glu2634Ter)	Pathogenic
2112678	NM_016343.4(CENPF):c.3312_3313del (p.Glu1104fs)	Pathogenic
224500	NM_016343.4(CENPF):c.2734G>T (p.Glu912Ter)	Pathogenic
224501	NM_016343.4(CENPF):c.171_199del (p.Asn57fs)	Pathogenic
2582638	NM_016343.4(CENPF):c.3703C>T (p.Gln1235Ter)	Pathogenic
280183	NM_016343.4(CENPF):c.8033dup (p.Asp2679fs)	Pathogenic
2880268	NM_016343.4(CENPF):c.756dup (p.Thr253fs)	Pathogenic
3572957	NM_016343.4(CENPF):c.3764C>A (p.Ser1255Ter)	Pathogenic
3572958	NM_016343.4(CENPF):c.3514_3515del (p.Glu1172fs)	Pathogenic
3683501	NM_016343.4(CENPF):c.6892C>T (p.Gln2298Ter)	Pathogenic
3764558	NM_016343.4(CENPF):c.8161-1G>C	Pathogenic
3896446	NM_016343.4(CENPF):c.3488_3503dup (p.Asn1168delinsLysThrTer)	Pathogenic
4699529	NM_016343.4(CENPF):c.3769G>T (p.Glu1257Ter)	Pathogenic
4717546	NM_016343.4(CENPF):c.8206G>T (p.Glu2736Ter)	Pathogenic
592054	NM_016343.4(CENPF):c.4986+1G>T	Pathogenic
619138	NM_016343.4(CENPF):c.5920dup (p.Thr1974fs)	Pathogenic
1049295	NM_016343.4(CENPF):c.6376_6387delinsTGAAAAGAA (p.Val2126_Glu2129delinsTer)	Likely pathogenic
1050538	NM_016343.4(CENPF):c.6387_6388insAA (p.Ala2130fs)	Likely pathogenic
1704133	NM_016343.4(CENPF):c.8451_8452del (p.Gln2818fs)	Likely pathogenic
1712558	NM_016343.4(CENPF):c.8322+1G>T	Likely pathogenic
224502	NM_016343.4(CENPF):c.9280C>T (p.Arg3094Ter)	Likely pathogenic
2442063	NM_016343.4(CENPF):c.2513C>A (p.Ser838Ter)	Likely pathogenic

SpliceAI

2847 predictions. Top by Δscore:

Variant	Effect	Δscore
1:214603317:GCAAG:G	donor_gain	1.0000
1:214603319:AAGG:A	donor_loss	1.0000
1:214603322:GTGAG:G	donor_loss	1.0000
1:214603323:T:G	donor_loss	1.0000
1:214613712:A:AG	acceptor_gain	1.0000
1:214613713:G:GC	acceptor_gain	1.0000
1:214613713:GT:G	acceptor_gain	1.0000
1:214613713:GTT:G	acceptor_gain	1.0000
1:214613713:GTTT:G	acceptor_gain	1.0000
1:214613713:GTTTA:G	acceptor_gain	1.0000
1:214613913:GAAG:G	donor_gain	1.0000
1:214613914:A:T	donor_gain	1.0000
1:214613914:AAG:A	donor_loss	1.0000
1:214613915:AGGTA:A	donor_loss	1.0000
1:214613916:GGTAC:G	donor_loss	1.0000
1:214613917:G:T	donor_loss	1.0000
1:214613918:T:G	donor_loss	1.0000
1:214614828:TTA:T	acceptor_loss	1.0000
1:214614829:TAGGT:T	acceptor_loss	1.0000
1:214614831:G:GA	acceptor_loss	1.0000
1:214615024:AAAAG:A	donor_loss	1.0000
1:214615025:AAAG:A	donor_loss	1.0000
1:214615027:AGGTA:A	donor_loss	1.0000
1:214615029:G:C	donor_loss	1.0000
1:214615030:T:G	donor_loss	1.0000
1:214619127:A:AG	acceptor_gain	1.0000
1:214619128:G:GG	acceptor_gain	1.0000
1:214619201:TTA:T	donor_gain	1.0000
1:214619218:AAAGT:A	donor_loss	1.0000
1:214619219:AAGTA:A	donor_loss	1.0000

AlphaMissense

20735 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:214613776:T:A	W8R	0.999
1:214613776:T:C	W8R	0.999
1:214613778:G:C	W8C	0.998
1:214613778:G:T	W8C	0.998
1:214613761:T:A	W3R	0.996
1:214613761:T:C	W3R	0.996
1:214613763:G:C	W3C	0.994
1:214613763:G:T	W3C	0.994
1:214613789:T:C	L12P	0.993
1:214613758:A:C	S2R	0.991
1:214613760:C:A	S2R	0.991
1:214613760:C:G	S2R	0.991
1:214613897:T:C	L48P	0.991
1:214619180:G:C	R178P	0.991
1:214629101:G:C	R375P	0.991
1:214613781:A:C	K9N	0.990
1:214613781:A:T	K9N	0.990
1:214614938:T:C	L90P	0.989
1:214613777:G:C	W8S	0.988
1:214613789:T:A	L12Q	0.988
1:214613822:T:C	L23P	0.988
1:214613843:T:C	L30P	0.988
1:214613876:T:C	L41P	0.988
1:214640038:G:C	R567P	0.988
1:214615022:T:C	L118P	0.987
1:214614980:T:C	L104P	0.986
1:214620730:T:C	F217L	0.986
1:214620732:C:A	F217L	0.986
1:214620732:C:G	F217L	0.986
1:214620736:T:A	W219R	0.986

dbSNP variants (sampled 300 via entrez): RS1000073170 (1:214656124 G>A), RS1000077625 (1:214639578 T>A,C), RS1000126007 (1:214607341 C>T), RS1000157059 (1:214607066 C>G,T), RS1000186164 (1:214640883 C>G,T), RS1000296755 (1:214653437 C>T), RS1000308701 (1:214601518 A>G), RS1000328879 (1:214653648 A>G,T), RS1000387095 (1:214612103 G>A), RS1000436057 (1:214658912 A>T), RS1000472428 (1:214614603 C>G), RS1000586748 (1:214664544 A>G), RS1000681886 (1:214601762 C>A,T), RS1000684220 (1:214650916 C>A), RS1000736157 (1:214651203 G>T)

Disease associations

OMIM: gene MIM:600236 | disease phenotypes: MIM:243605, MIM:616369, MIM:615872, MIM:220100

GenCC curated gene-disease

Disease	Classification	Inheritance
Stromme syndrome	Strong	Autosomal recessive

Mondo (4): Stromme syndrome (MONDO:0009477), primary ciliary dyskinesia 29 (MONDO:0014378), microcephaly (MONDO:0001149), cystinuria (MONDO:0009067)

Orphanet (4): Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome (Orphanet:444069), Stromme syndrome (Orphanet:506307), Primary ciliary dyskinesia (Orphanet:244), Cystinuria (Orphanet:214)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000482	Microcornea
HP:0000490	Deeply set eye
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000609	Optic nerve hypoplasia
HP:0000612	Iris coloboma
HP:0000647	Sclerocornea
HP:0000659	Peters anomaly
HP:0001274	Agenesis of corpus callosum
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001747	Accessory spleen
HP:0002000	Short columella
HP:0002247	Duodenal atresia
HP:0002566	Intestinal malrotation
HP:0003198	Myopathy
HP:0003577	Congenital onset
HP:0003826	Stillbirth
HP:0005235	Jejunal atresia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001095_1	Response to antineoplastic agents	5.000000e-06
GCST006483_39	Lung function (FVC)	4.000000e-09
GCST009441_15	Age-related cognitive decline (memory) (slope of z-scores)	9.000000e-06
GCST010146_41	Serum immune biomarker levels	6.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity
EFO:0007710	cognitive decline measurement
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003555	Cystinuria	C12.050.351.968.419.815.885.250; C12.200.777.419.815.885.250; C12.950.419.815.885.250; C16.320.831.885.250
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C565460	Jejunal Atresia with Microcephaly and Ocular Anomalies (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	4
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	4
Valproic Acid	affects expression, decreases expression, decreases methylation	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Benzo(a)pyrene	decreases expression	3
Tobacco Smoke Pollution	increases methylation, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
Particulate Matter	increases abundance, affects cotreatment, decreases expression	3
arsenite	affects binding, decreases reaction, increases methylation	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Zoledronic Acid	decreases expression, decreases farnesylation	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cadmium	decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Coumestrol	increases expression, affects reaction, affects cotreatment	2
Doxorubicin	decreases expression	2
Hydrogen Peroxide	affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Lithium Chloride	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Genistein	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
SP2509	affects binding, decreases reaction, decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02125721	PHASE4	COMPLETED	Effect of Increasing Doses of Cystine Binding Thiol Drugs on Cystine Capacity in Patients With Cystinuria
NCT02910531	PHASE2	COMPLETED	Lipoic Acid Supplement for Cystine Stone
NCT02942420	PHASE2	UNKNOWN	Bucillamine Phase 2 Trial in Patients With Cystinuria
NCT03663855	PHASE2	COMPLETED	Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria
NCT04818034	PHASE2	COMPLETED	The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study
NCT05058859	PHASE2	WITHDRAWN	Long Term Clinical Efficacy of Sodium-glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics
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)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.
NCT04137978	PHASE2/PHASE3	WITHDRAWN	Study Evaluating Patients With Cystinuria
NCT04147871	PHASE2/PHASE3	WITHDRAWN	Study Evaluating Patients With Cystinuria and Efficacy and Safety Exploratory Study in the Youngest Children
NCT00381849	PHASE1/PHASE2	COMPLETED	Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones
NCT00169806	Not specified	ACTIVE_NOT_RECRUITING	Randall’s Plaque Study: Pathogenesis and Relationship to Nephrolithiasis
NCT00588562	Not specified	RECRUITING	Rare Kidney Stone Consortium Patient Registry
NCT02026388	Not specified	RECRUITING	Rare Kidney Stone Consortium Biobank
NCT02120105	Not specified	COMPLETED	Cystine Capacity Clinical Study (CysCap)
NCT02124395	Not specified	COMPLETED	Health-related Quality of Life in Rare Kidney Stone
NCT02538016	Not specified	COMPLETED	TCUPS- Tolvaptan Use in Cystinuria and Urolithiasis: A Pilot Study
NCT02780297	Not specified	RECRUITING	Prospective Research Rare Kidney Stones (ProRKS)
NCT03539926	Not specified	UNKNOWN	This Study Evaluates the Superiority of Daily Self-pH Monitorization of Lit-control®pH Meter Compared to the Monitorization of Reactive Strips (Standard of Care).
NCT03836144	Not specified	COMPLETED	Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria
NCT05048563	Not specified	COMPLETED	Registry of Thiola EC Therapy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases