CEP43

Chr 6

centrosomal protein 43

Also known as: FGFR1OP, FOP

NCBI Gene: 11116 ENSG00000213066 UniProt: O95684 OMIM: 605392

This gene encodes a centrosomal protein that anchors microtubules to centrosomes and is required for ciliation. Mutations cause myeloproliferative disorder through chromosomal translocations with FGFR1, with inheritance pattern not clearly established from available data. The gene shows low constraint to loss-of-function variants, suggesting tolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.731 OMIM phenotype

Clinical Summary— CEP43

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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

1 unique Pathogenic / Likely Pathogenic· 64 VUS of 94 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.001

Z-score 2.50

OE 0.42 (0.25–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.19Z-score

OE missense 1.04 (0.93–1.17)

199 obs / 191.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.42 (0.25–0.73)

0≤0.351.4

Missense OE?1.04 (0.93–1.17)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 9 / 21.5Missense obs/exp: 199 / 191.5Syn Z: 0.22

This gene — mechanism propensity

0.74top 25%

GOF

0.4184th %ile

LOF

0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS64

Likely Benign2

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	63	1	64
Likely Benign	2	0	2
Benign	1	0	1
Total	66	2	68

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

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56 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap CEP43 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →