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GeneE
8 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PPP1R35
protein phosphatase 1 regulatory subunit 35
Chromosome 7 Β· 7q22.1
NCBI Gene: 221908Ensembl: ENSG00000160813.8HGNC: HGNC:28320UniProt: Q8TAP8
13PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingpositive regulation of centriole elongationcentriolecentrosomeProgressive microcephalyhereditary hyperferritinemia with congenital cataractsearly-onset non-syndromic cataractCataract-microcornea syndrome
✦AI Summary

PPP1R35 (protein phosphatase 1 regulatory subunit 35) is a centrosomal protein essential for centriole elongation and centriole-to-centrosome conversion during cellular division. PPP1R35 localizes to the proximal lumen above the cartwheel within centrioles 1 and functions downstream of the microcephaly protein RTTN by promoting recruitment of microtubule-binding elongation machinery 12. This interaction is critical for proper centriole maturation and centrosome formation 3. Beyond its centrosomal role, PPP1R35 is required for primary cilia assembly and notochord morphogenesis during murine development 4. Clinically, PPP1R35 dysfunction is associated with primary microcephaly (MCPH), a severe neurodevelopmental disorder. A homozygous frameshift indel in PPP1R35 was identified in multiple consanguineous families presenting with severe microcephaly, pachygyria, and global developmental delay 5. Notably, PPP1R35 is phosphorylated by CDKL5, a protein kinase mutated in CDKL5 Deficiency Disorder (CDD), an epileptic encephalopathy affecting children 6. The impaired centriole elongation and cilia morphology resulting from PPP1R35 dysfunction may contribute to neurodevelopmental pathology in CDD.

Sources cited
1
PPP1R35 is a centrosomal protein localized to the proximal lumen above the cartwheel that is critical for centriole elongation and acts downstream of RTTN
PMID: 30168418
2
PPP1R35 is required for centriole-to-centrosome conversion and CEP295 recruitment
PMID: 30230954
3
PPP1R35 (Rcd4) is required during centriole elongation and recruitment of centriolar components in Drosophila
PMID: 38796459
4
Homozygous frameshift indel in PPP1R35 causes primary microcephaly with severe developmental delay in consanguineous families
PMID: 36598158
5
Ppp1r35 is required for ciliogenesis, notochord morphogenesis, and cell-cycle progression during murine development; loss causes developmental delay and absence of primary cilia
PMID: 32628936
6
PPP1R35 is a phosphorylation target of CDKL5 and is critical for centriole elongation and cilia morphology, processes impaired in CDKL5 Deficiency Disorder
PMID: 39136782
Disease Associationsβ“˜20
Progressive microcephalyOpen Targets
0.34Weak
hereditary hyperferritinemia with congenital cataractsOpen Targets
0.05Suggestive
early-onset non-syndromic cataractOpen Targets
0.05Suggestive
Cataract-microcornea syndromeOpen Targets
0.05Suggestive
Cataract with Y-shaped suture opacitiesOpen Targets
0.04Suggestive
Total congenital cataractOpen Targets
0.04Suggestive
Juvenile cataract - microcornea - renal glucosuriaOpen Targets
0.04Suggestive
juvenile cataract-microcornea-renal glucosuria syndromeOpen Targets
0.04Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.04Suggestive
isolated ectopia lentisOpen Targets
0.04Suggestive
granular corneal dystrophy type IOpen Targets
0.04Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.04Suggestive
Posterior polar cataractOpen Targets
0.04Suggestive
exfoliation syndromeOpen Targets
0.04Suggestive
cataract 35Open Targets
0.03Suggestive
Partial congenital cataractOpen Targets
0.03Suggestive
cataract - microcornea syndromeOpen Targets
0.03Suggestive
cataract 5 multiple typesOpen Targets
0.03Suggestive
exercise-induced hyperinsulinismOpen Targets
0.03Suggestive
glycogen storage disorder due to hepatic glycogen synthase deficiencyOpen Targets
0.03Suggestive
Pathogenic Variants1
NM_145030.4(PPP1R35):c.753_*3delinsCG (p.Trp251fs)Pathogenic
Progressive microcephaly
β˜…β˜†β˜†β˜†2022β†’ Residue 251
View on ClinVar β†—
Related Genes
RTTNProtein interaction74%CCDC15Shared pathway33%CEP120Shared pathway29%TAPT1Shared pathway25%SAXO1Shared pathway25%CEP295Shared pathway22%
Tissue Expression6 tissues
Ovary
100%
Liver
94%
Lung
76%
Bone Marrow
51%
Brain
34%
Heart
26%
Gene Interaction Network
Click a node to explore
PPP1R35RTTNCCDC15CEP120TAPT1SAXO1CEP295
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8TAP8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.91LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.50 [1.06–1.91]
RankingsWhere PPP1R35 stands among ~20K protein-coding genes
  • #16,264of 20,598
    Most Researched13
  • #5,457of 5,498
    Most Pathogenic Variants1
  • #17,339of 17,882
    Most Constrained (LOEUF)1.91
Genes detectedPPP1R35
Sources retrieved8 papers
Response timeβ€”
πŸ“„ Sources
8β–Ό
1
Novel CDKL5 targets identified in human iPSC-derived neurons.
PMID: 39136782
Cell Mol Life Sci Β· 2024
1.00
2
9-fold symmetry is not essential for centriole elongation and formation of new centriole-like structures.
PMID: 38796459
Nat Commun Β· 2024
0.88
3
A biallelic frameshift indel in PPP1R35 as a cause of primary microcephaly.
PMID: 36598158
Am J Med Genet A Β· 2023
0.75
4
PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN.
PMID: 30168418
Elife Β· 2018
0.63
5
Protein phosphatase 1 regulatory subunit 35 is required for ciliogenesis, notochord morphogenesis, and cell-cycle progression during murine development.
PMID: 32628936
Dev Biol Β· 2020
0.50