CEP43

Chr 6

centrosomal protein 43

Also known as: FGFR1OP, FOP

NCBI Gene: 11116ENSG00000213066UniProt: O95684

This gene encodes a largely hydrophilic centrosomal protein that is required for anchoring microtubules to subcellular structures. A t(6;8)(q27;p11) chromosomal translocation, fusing this gene and the fibroblast growth factor receptor 1 (FGFR1) gene, has been found in cases of myeloproliferative disorder. The resulting chimeric protein contains the N-terminal leucine-rich region of this encoded protein fused to the catalytic domain of FGFR1. Alterations in this gene may also be associated with Crohn's disease, Graves' disease, and vitiligo. Alternatively spliced transcript variants that encode different proteins have been identified. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

Myeloproliferative disorderMIM #605392
130
ClinVar variants
54
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CEP43
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 Pathogenic / Likely Pathogenic· 73 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.73LOEUF
pLI 0.001
Z-score 2.50
OE 0.42 (0.25–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.19Z-score
OE missense 1.04 (0.93–1.17)
199 obs / 191.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.25–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.93–1.17)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 9 / 21.5Missense obs/exp: 199 / 191.5Syn Z: 0.22

ClinVar Variant Classifications

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic3
VUS73
Likely Benign2
Benign1
51
Pathogenic
3
Likely Pathogenic
73
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
51
0
51
Likely Pathogenic
0
0
3
0
3
VUS
0
63
10
0
73
Likely Benign
0
2
0
0
2
Benign
0
1
0
0
1
Total066640130

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

View in ClinVar →

Protein Context — Lollipop Plot

CEP43 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myeloproliferative disorder

MIM #605392

Disorder mapped to chromosomal region

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Architecture of RabL2-associated complexes at the ciliary base: A structural modeling perspective: Deciphering the structural organization of ciliary RabL2 complexes.
Boegholm N et al.·Bioessays
2024Functional
rs9459874 and rs1012656 in CCR6/FGFR1OP confer susceptibility to primary biliary cholangitis.
Hitomi Y et al.·J Autoimmun
2022Meta-analysis
Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls.
Kang X et al.·Carcinogenesis
2016Meta-analysis
Mutation of FOP/FGFR1OP in mice recapitulates human short rib-polydactyly ciliopathy.
Cabaud O et al.·Hum Mol Genet
2018
[FGFR1 and MOZ, two key genes involved in malignant hemopathies linked to rearrangements within the chromosomal region 8p11-12].
Pébusque MJ et al.·Bull Cancer
2000Review
Molecular classification and pathogenesis of eosinophilic disorders: 2005 update.
Gotlib J·Acta Haematol
2005Review
Functional characterization of a novel FGFR1OP-RET rearrangement in hematopoietic malignancies.
Bossi D et al.·Mol Oncol
2014Functional
Association between FGFR1OP2/wit3.0 polymorphisms and residual ridge resorption of mandible in Korean population.
Kim JH et al.·PLoS One
2012
Dianhydrogalactitol, a potential multitarget agent, inhibits glioblastoma migration, invasion, and angiogenesis.
Jiang X et al.·Biomed Pharmacother
2017
FGFR1OP tagSNP but not CCR6 polymorphisms are associated with Vogt-Koyanagi-Harada syndrome in Chinese Han.
Yi X et al.·PLoS One
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools