CENPF

Chr 1AR

centromere protein F

Also known as: CENF, CILD31, PRO1779, STROMS, hcp-1

NCBI Gene: 1063 ENSG00000117724 UniProt: P49454 OMIM: 600236

The encoded protein is a component of the centromere-kinetochore complex that associates with kinetochores from late G2 through early anaphase and is essential for proper chromosome segregation during mitosis. Loss-of-function mutations cause Stromme syndrome, an autosomal recessive disorder characterized by intestinal atresia, microcephaly, and ocular abnormalities. The pathogenic mechanism involves de novo dominant effects despite the recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.731 OMIM phenotype

Clinical Summary— CENPF

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

65 unique Pathogenic / Likely Pathogenic· 530 VUS of 953 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CENPF

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 4.14

OE 0.61 (0.51–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.03Z-score

OE missense 1.00 (0.96–1.05)

1473 obs / 1469.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.51–0.73)

0≤0.351.4

Missense OE?1.00 (0.96–1.05)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 79 / 129.9Missense obs/exp: 1473 / 1469.8Syn Z: -0.30

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongCENPF-related Stromme syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.74top 25%

GOF

0.6248th %ile

LOF

0.2774th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

953 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27

Likely Pathogenic38

VUS530

Likely Benign203

Benign96

Conflicting30

Pathogenic

Likely Pathogenic

530

VUS

203

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	27	0	0	0	27
Likely Pathogenic	38	0	0	0	38
VUS	6	515	6	3	530
Likely Benign	0	39	53	111	203
Benign	0	31	51	14	96
Conflicting	—				30
Total	71	585	110	128	924

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap CENPF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →