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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CEP104
centrosomal protein 104
Chromosome 1 Β· 1p36.32
NCBI Gene: 9731Ensembl: ENSG00000116198.15HGNC: HGNC:24866UniProt: O60308
29PubMed Papers
22Diseases
0Drugs
51Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
identical protein bindingcentrioleciliumprotein bindingJoubert syndrome 25intellectual developmental disorder, autosomal recessive 77Joubert syndrome and related disordersJoubert syndrome
✦AI Summary

CEP104 is a centrosomal and ciliary tip protein essential for ciliogenesis and ciliary structural integrity 1. It contains a tubulin-binding TOG (tumor overexpressed gene) domain and a C2HC zinc finger array that enable interaction with tubulin and the kinase Nek1 2. CEP104 functions as part of a ciliary tip protein module including CSPP1, TOGARAM1, ARMC9, and CCDC66 3. This complex regulates axonemal microtubule dynamics by inhibiting both microtubule growth and shortening, with TOGARAM1 counteracting growth inhibition to produce slow, processive microtubule elongation characteristic of axonemes 4. The CEP104-CSPP1 interaction specifically regulates axoneme length and is required for Hedgehog signaling competence in primary cilia 1. Pathogenic CEP104 variants cause two distinct neurodevelopmental phenotypes. Most commonly, mutations cause Joubert syndrome 25 (JBTS25), a ciliopathy characterized by hindbrain malformation and the pathognomonic molar tooth sign 5. However, CEP104 dysfunction also causes intellectual developmental disorder with broader clinical variabilityβ€”some patients present with intellectual disability and hypotonia without JBTS-associated brain anomalies 6. CEP104 mutations result in shortened cilia with decreased axonemal post-translational modifications 3, disrupting both developmental signaling and sensory ciliary functions critical for normal neurodevelopment 7.

Sources cited
1
CEP104 is a centrosomal and ciliary tip protein; CEP104-CSPP1 complex regulates axoneme length and Hedgehog signaling competence
PMID: 31412255
2
CEP104 contains a tubulin-binding TOG domain and C2HC zinc finger array; interacts with Nek1 kinase
PMID: 28017521
3
CEP104 is part of a ciliary tip protein module; dysfunction causes short cilia with decreased axonemal acetylation and polyglutamylation
PMID: 32453716
4
CEP104 and CSPP1 inhibit microtubule growth/shortening; TOGARAM1 overcomes this inhibition; the module produces slow processive microtubule elongation
PMID: 39856351
5
CEP104 mutations cause Joubert syndrome with cerebellar vermis hypoplasia and molar tooth sign
PMID: 31625690
6
CEP104 mutations can cause intellectual disability without JBTS-associated brain malformations, indicating broader disease phenotypes
PMID: 35359234
7
CEP104 mutations cause intellectual disability and ciliopathy-associated features; reduced CEP104 expression in patient cells
PMID: 34196201
Disease Associationsβ“˜22
Joubert syndrome 25Open Targets
0.75Strong
intellectual developmental disorder, autosomal recessive 77Open Targets
0.53Moderate
Joubert syndrome and related disordersOpen Targets
0.52Moderate
Joubert syndromeOpen Targets
0.51Moderate
ciliopathyOpen Targets
0.40Moderate
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
Global developmental delayOpen Targets
0.33Weak
cerebellar ataxiaOpen Targets
0.33Weak
DystoniaOpen Targets
0.33Weak
dystonic disorderOpen Targets
0.33Weak
autism spectrum disorderOpen Targets
0.30Weak
genetic disorderOpen Targets
0.19Weak
asthmaOpen Targets
0.06Suggestive
alcohol drinkingOpen Targets
0.05Suggestive
malignant renal pelvis neoplasmOpen Targets
0.04Suggestive
response to diisocyanateOpen Targets
0.04Suggestive
psoriatic arthritisOpen Targets
0.03Suggestive
VertigoOpen Targets
0.02Suggestive
smoking initiationOpen Targets
0.02Suggestive
placenta praeviaOpen Targets
0.02Suggestive
Intellectual developmental disorder, autosomal recessive 77UniProt
Joubert syndrome 25UniProt
Pathogenic Variants51
NM_014704.4(CEP104):c.895C>T (p.Arg299Ter)Pathogenic
CEP104-related disorder|Intellectual developmental disorder, autosomal recessive 77;Joubert syndrome 25|Joubert syndrome 25
β˜…β˜…β˜†β˜†2026β†’ Residue 299
NM_014704.4(CEP104):c.808A>T (p.Lys270Ter)Pathogenic
Intellectual developmental disorder, autosomal recessive 77;Joubert syndrome 25|Joubert syndrome 25|Autosomal recessive CEP104-related disorders
β˜…β˜…β˜†β˜†2025β†’ Residue 270
NM_014704.4(CEP104):c.1485+1G>ALikely pathogenic
Joubert syndrome and related disorders|Sarcoma|Joubert syndrome 25
β˜…β˜…β˜†β˜†2025
NM_014704.4(CEP104):c.1051_1054del (p.Thr351fs)Pathogenic
Joubert syndrome and related disorders|Intellectual developmental disorder, autosomal recessive 77|Intellectual developmental disorder, autosomal recessive 77;Joubert syndrome 25|Joubert syndrome 25
β˜…β˜…β˜†β˜†2025β†’ Residue 351
NM_014704.4(CEP104):c.2081_2084del (p.Gln694fs)Pathogenic
not provided|Joubert syndrome 25
β˜…β˜…β˜†β˜†2025β†’ Residue 694
NM_014704.4(CEP104):c.163C>T (p.Arg55Ter)Pathogenic
Joubert syndrome 25|not provided|Joubert syndrome 25;Intellectual developmental disorder, autosomal recessive 77
β˜…β˜…β˜†β˜†2024β†’ Residue 55
NM_014704.4(CEP104):c.2286del (p.Glu762fs)Likely pathogenic
Joubert syndrome and related disorders|Joubert syndrome 25;Intellectual developmental disorder, autosomal recessive 77
β˜…β˜…β˜†β˜†2024β†’ Residue 762
NM_014704.4(CEP104):c.759T>G (p.Tyr253Ter)Pathogenic
Joubert syndrome 25|Intellectual developmental disorder, autosomal recessive 77;Joubert syndrome 25
β˜…β˜…β˜†β˜†2024β†’ Residue 253
NM_014704.4(CEP104):c.300_301del (p.Leu100_Cys101insTer)Pathogenic
Joubert syndrome 25
β˜…β˜…β˜†β˜†2023β†’ Residue 100
NM_014704.4(CEP104):c.1879G>T (p.Glu627Ter)Pathogenic
See cases|Joubert syndrome 25
β˜…β˜…β˜†β˜†2022β†’ Residue 627
NM_014704.4(CEP104):c.1891C>T (p.Arg631Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2019β†’ Residue 631
NM_014704.4(CEP104):c.1351C>T (p.Arg451Ter)Pathogenic
Joubert syndrome 25
β˜…β˜†β˜†β˜†2026β†’ Residue 451
NM_014704.4(CEP104):c.1659+1G>ALikely pathogenic
Joubert syndrome 25
β˜…β˜†β˜†β˜†2025
NM_014704.4(CEP104):c.1031del (p.Lys344fs)Pathogenic
Joubert syndrome 25
β˜…β˜†β˜†β˜†2025β†’ Residue 344
NM_014704.4(CEP104):c.2080_2083del (p.Gln694fs)Pathogenic
Joubert syndrome and related disorders
β˜…β˜†β˜†β˜†2025β†’ Residue 694
NM_014704.4(CEP104):c.891+1G>ALikely pathogenic
Joubert syndrome and related disorders
β˜…β˜†β˜†β˜†2025
NM_014704.4(CEP104):c.1317+1delLikely pathogenic
Joubert syndrome and related disorders
β˜…β˜†β˜†β˜†2025
NM_014704.4(CEP104):c.643C>T (p.Arg215Ter)Pathogenic
Intellectual developmental disorder, autosomal recessive 77|Joubert syndrome and related disorders
β˜…β˜†β˜†β˜†2025β†’ Residue 215
NM_014704.4(CEP104):c.2490_2491del (p.His830fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 830
NM_014704.4(CEP104):c.1317+2T>GLikely pathogenic
Joubert syndrome 25
β˜…β˜†β˜†β˜†2025
View on ClinVar β†—
Related Genes
CCP110Protein interaction100%CEP97Protein interaction83%LRRC47Protein interaction72%TOGARAM1Co-mentioned in literature33%ARMC9Co-mentioned in literature20%CSPP1Co-mentioned in literature20%
Tissue Expression6 tissues
Brain
100%
Heart
96%
Liver
91%
Ovary
73%
Lung
69%
Bone Marrow
54%
Gene Interaction Network
Click a node to explore
CEP104CCP110CEP97LRRC47TOGARAM1ARMC9CSPP1
PROTEIN STRUCTURE
Preparing viewer…
PDB5LPI Β· 1.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.70 [0.58–0.85]
RankingsWhere CEP104 stands among ~20K protein-coding genes
  • #12,121of 20,598
    Most Researched29
  • #1,318of 5,498
    Most Pathogenic Variants51 Β· top quartile
  • #7,393of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedCEP104
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301500
1.00
2
Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome.
PMID: 32453716
J Clin Invest Β· 2020
0.90
3
CEP104 gene may involve in the pathogenesis of a new developmental disorder other than joubert syndrome.
PMID: 35359234
Mol Biol Rep Β· 2022
0.80
4
The Ciliopathy-Associated Cep104 Protein Interacts with Tubulin and Nek1 Kinase.
PMID: 28017521
Structure Β· 2017
0.70
5
A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling.
PMID: 31412255
Cell Rep Β· 2019
0.60