CENPF

centromere protein F

Basic information

Region (hg38): 1:214603185-214664574

Links

ENSG00000117724

∙ NCBI:1063 ∙ OMIM:600236 ∙ HGNC:1857 ∙ Uniprot:P49454 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Stromme syndrome (Strong), mode of inheritance: AR
Stromme syndrome (Strong), mode of inheritance: AR
Stromme syndrome (Strong), mode of inheritance: AR
Stromme syndrome (Supportive), mode of inheritance: AR
Stromme syndrome (Supportive), mode of inheritance: AR
Stromme syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stromme syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Gastrointestinal; Neurologic; Renal	25564561; 26820108

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CENPF gene.

Inborn_genetic_diseases (376 variants)
not_provided (339 variants)
Stromme_syndrome (67 variants)
CENPF-related_disorder (67 variants)
not_specified (47 variants)
Neurodevelopmental_delay (2 variants)
Microcephaly (2 variants)
Susceptibility_to_severe_COVID-19 (1 variants)
Cystinuria (1 variants)
Primary_ciliary_dyskinesia_29 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CENPF gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016343.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	102 clinvar	6 clinvar	111
missense		1 clinvar	459 clinvar	61 clinvar	9 clinvar	530
nonsense	12 clinvar	13 clinvar	2 clinvar			27
start loss						0
frameshift	8 clinvar	15 clinvar	2 clinvar			25
splice donor/acceptor (+/-2bp)	3 clinvar	7 clinvar	3 clinvar			13
Total	23	36	469	163	15

Highest pathogenic variant AF is 0.00031911235

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CENPF	protein_coding	protein_coding	ENST00000366955	19	61394

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.88e-36	1.00	125388	0	360	125748	0.00143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0297	1473	1.47e+3	1.00	0.0000728	20620
Missense in Polyphen		375	400.25	0.93691		6078
Synonymous	-0.297	577	568	1.02	0.0000297	5506
Loss of Function	4.14	79	130	0.608	0.00000637	1848

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00191	0.00190
Ashkenazi Jewish	0.00189	0.00189
East Asian	0.000748	0.000707
Finnish	0.000420	0.000416
European (Non-Finnish)	0.00192	0.00187
Middle Eastern	0.000748	0.000707
South Asian	0.00162	0.00157
Other	0.00172	0.00163

dbNSFP

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:12974617, ECO:0000269|PubMed:17600710, ECO:0000269|PubMed:7542657, ECO:0000269|PubMed:7651420}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:25564561, ECO:0000269|PubMed:26820108}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Mitotic G2-G2-M phases;Gastric Cancer Network 1;Signal Transduction;Polo-like kinase mediated events;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;G2/M Transition;Mitotic G2-G2/M phases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;FOXM1 transcription factor network (Consensus)

Recessive Scores

pRec: 0.148

Intolerance Scores

loftool: 0.968
rvis_EVS: 4.96
rvis_percentile_EVS: 99.81

Haploinsufficiency Scores

pHI: 0.821
hipred: Y
hipred_score: 0.647
ghis: 0.543

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: E
essential_gene_gene_trap: H
gene_indispensability_pred: E
gene_indispensability_score: 0.730

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Cenpf
Phenotype: muscle phenotype; cellular phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name: cenpf
Affected structure: trunk
Phenotype tag: abnormal
Phenotype quality: curved

Gene ontology

Biological process: mitotic cell cycle;kidney development;chromosome segregation;mitotic spindle assembly checkpoint;muscle organ development;cell population proliferation;regulation of G2/M transition of mitotic cell cycle;protein transport;regulation of striated muscle tissue development;ventricular system development;cell differentiation;response to drug;negative regulation of transcription, DNA-templated;cell division;metaphase plate congression;kinetochore assembly;regulation of cell cycle;DNA biosynthetic process
Cellular component: chromosome, centromeric region;kinetochore;chromatin;spindle pole;condensed chromosome outer kinetochore;nucleus;nuclear envelope;nucleoplasm;cytoplasm;centrosome;spindle;cytosol;axoneme;nuclear matrix;midbody;ciliary basal body;pronucleus;perinuclear region of cytoplasm;ciliary transition fiber
Molecular function: chromatin binding;protein binding;protein C-terminus binding;transcription factor binding;protein homodimerization activity;dynein complex binding