CENPF

protein-coding

centromere protein F

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_016343.4

Inheritance

ClinVar variants

P:90U:543B:241

Top phenotype

Stromme syndrome

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr1:214,603,185-214,664,574

External References & Databases

Ensembl (ENSG00000117724)

Transcript & Mutation Effects

hg38 • Region Span ~61.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Stromme syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009477

Submitter: Orphanet

Stromme syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009477

Submitter: Orphanet

Stromme syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009477

Submitter: Labcorp Genetics (formerly Invitae)

Stromme syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009477

Submitter: Illumina

Stromme syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009477

Submitter: G2P

Stromme syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009477

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Stromme syndromeAR

Manifestation: Craniofacial; Gastrointestinal; Neurologic; Renal

Intervention: General

Rationale: 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

Refs: 25564561; 26820108

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CENPF variants in ClinVar

13 Conditions Cataloged

Inborn genetic diseasesTotal: 427

not providedTotal: 401

not specifiedTotal: 138

CENPF-related disorderTotal: 110

Stromme syndromeTotal: 84

Abnormal meiosisTotal: 4

Female infertilityTotal: 4

Neurodevelopmental delayTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016343.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	155 clinvar	1 clinvar	161
missense			526 clinvar	78 clinvar	7 clinvar	611
nonsense	13 clinvar	27 clinvar	2 clinvar			42
start loss						0
frameshift	9 clinvar	29 clinvar	2 clinvar			40
splice donor/acceptor (+/-2bp)	4 clinvar	8 clinvar	8 clinvar			20
Total	26	64	543	233	8	874

Highest pathogenic variant AF is 0.00031911235

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016343.4	RefSeq	NP_057427.3	19	MANE Select
ENST00000366955.8	Ensembl	ENSP00000355922.3	19	MANE Select
ENST00000706765.1	Ensembl	ENSP00000516538.1	18	Standard
ENST00000706765.2	Ensembl	ENSP00000516538.1	18	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cenpf	Danio rerio	Structure: trunk Quality: curved abnormal

Gene / Model

Organism

Observed Phenotype

cenpf

Danio rerio

Structure: trunk

Quality: curved

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

mitotic cell cycle
kidney development
chromosome segregation
mitotic spindle assembly checkpoint
muscle organ development

Molecular Function

chromatin binding
protein binding
protein C-terminus binding
transcription factor binding
protein homodimerization activity

Cellular Component

chromosome, centromeric region
kinetochore
chromatin
spindle pole
condensed chromosome outer kinetochore

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366955
Coding exons: 19
Length: 61394
Individuals with no LoFs: 125388
Homozygous LoFs: 0
Heterozygous LoFs: 360
Defined: 125748
p: 0.00143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0297	1473	1.47e+3	1.00	0.0000728	20620
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00081	0.00080	rare
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.0019	0.0019	notable
East Asian	0.00075	0.00071	rare
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.0019	0.0019	notable
South Asian	0.0016	0.0016	notable
Other	0.0017	0.0016	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.968
RVIS EVS: 4.96
RVIS percentile EVS: 99.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.730

Gene Damage Prediction

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