Affinage

POC1A

POC1 centriolar protein homolog A · UniProt Q8NBT0

Length
407 aa
Mass
45.0 kDa
Annotated
2026-06-10
19 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POC1A is a WD40-repeat centriolar protein that builds and stabilizes the centriole inner scaffold and is required for centriole integrity, duplication, mitotic spindle organization, and ciliogenesis (PMID:39543170, PMID:23015594). It forms a heterodimer with POC1B in the centriole lumen, where the POC1A WD40 domain faces the lumen and interacts with POC5, while POC1B sits closer to the centriole wall; together with FAM161A and MDM1 this assembly organizes an inner scaffold interaction network, and the POC1A–POC5 interaction with POC5 tetramerization is essential for inner scaffold formation and centriole stability (PMID:39543170). POC1A and POC1B localize to centrioles and spindle poles and are stably incorporated into parental centrioles, with the two paralogs acting redundantly for incorporation into nascent centrioles—co-depletion, but not loss of either alone, abolishes centriole maturation and duplication and produces monopolar or unequal spindles (PMID:23015594). Loss-of-function in patient cells and mouse models causes centrosome amplification, multipolar spindles, and defective cilia, and in mice additionally disrupts spermatogenesis and chondrocyte organization in the growth plate (PMID:22840364, PMID:26496357, PMID:26336158). Human truncating and missense mutations in POC1A cause a developmental ciliopathy/skeletal phenotype, with patient cells showing abnormal centrosome number, defective ciliogenesis, and disrupted Golgi assembly and trafficking (PMID:22840364, PMID:22840363, PMID:26162852). In specific cellular contexts POC1A loss impairs adipocyte differentiation, induces senescence, and alters insulin-receptor localization producing insulin/IGF-1 resistance (PMID:38245004), while its overexpression drives epithelial–mesenchymal transition in breast cancer cells through STAT3 signaling (PMID:40830747).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2012 High

    Established that POC1A is a centriolar/spindle-pole protein functionally redundant with its paralog POC1B for centriole duplication and integrity, resolving whether the two POC1 proteins act independently.

    Evidence Isoform-specific antibodies and single/double RNAi depletion with live-cell imaging and incorporation assays in human cells

    PMID:23015594

    Open questions at the time
    • Did not resolve the molecular architecture by which POC1A is incorporated into the centriole lumen
    • Differential mitotic phosphorylation of POC1B vs POC1A left functionally unexplained
    • No structural model of the POC1A interaction network
  2. 2012 Medium

    Linked POC1A loss-of-function to a human disease phenotype by showing truncating mutations cause defective ciliogenesis and abnormal mitotic spindles, connecting centriole function to organismal pathology.

    Evidence Patient cell analysis plus siRNA knockdown in fibroblasts with cilia and spindle immunofluorescence

    PMID:22840364

    Open questions at the time
    • Single lab; ciliogenesis defect mechanism not dissected at molecular level
    • Did not address why centriole defects produce specific tissue phenotypes
  3. 2012 Medium

    Extended POC1A function beyond centriole/spindle to Golgi assembly and membrane trafficking, showing a missense mutation disrupts centrosome number, Golgi morphology, and toxin trafficking.

    Evidence Patient-derived cells with centrosome/Golgi immunofluorescence and cholera-toxin trafficking assay

    PMID:22840363

    Open questions at the time
    • Whether Golgi/trafficking defects are direct or secondary to centrosome dysfunction not established
    • Single missense allele; mechanism of trafficking link unknown
  4. 2015 High

    Demonstrated in vivo requirement for POC1A across multiple tissues, showing it is essential for cilia, spindle bipolarity, spermatogenesis, and chondrocyte organization.

    Evidence Mouse insertional mutant with cilia/spindle assays, growth-plate histology, and spermatogonial stem cell transplantation

    PMID:26496357

    Open questions at the time
    • Tissue-specific molecular basis of germ cell and chondrocyte phenotypes not resolved
    • Did not map which centriole functions drive each tissue defect
  5. 2015 Medium

    Refined the disease mechanism by showing distinct POC1A mutations cause supernumerary centrosomes and multipolar spindles, in one case implicating the regulator p80-katanin.

    Evidence Patient fibroblast immunofluorescence, gene expression array, and DNA-content and centrosome/spindle analyses

    PMID:26162852 PMID:26336158

    Open questions at the time
    • Functional relationship between POC1A and p80-katanin not directly tested
    • Variable ciliary phenotype across alleles unexplained
    • Centrosome clustering as compensatory mechanism not mechanistically dissected
  6. 2024 High

    Resolved the molecular architecture of the centriole inner scaffold, placing the POC1A–POC1B heterodimer at its core and defining the POC1A–POC5–FAM161A–MDM1 interaction network required for centriole stability.

    Evidence Co-IP/pulldown interaction mapping with domain-level localization and single/double genetic disruption

    PMID:39543170

    Open questions at the time
    • High-resolution structure of the assembled inner scaffold not determined
    • Order and regulation of scaffold assembly during the cell cycle unresolved
  7. 2024 Medium

    Connected POC1A loss to metabolic dysfunction, showing impaired adipocyte differentiation, senescence, and mislocalized insulin receptors causing hormone resistance.

    Evidence Patient fibroblasts and CRISPR-deleted adipose stem cells with differentiation, senescence, signaling, and receptor-localization assays

    PMID:38245004

    Open questions at the time
    • Mechanistic link between centriole/cilia defect and insulin-receptor mislocalization not established
    • Single lab; causality of senescence in hormone resistance unclear
  8. 2025 Medium

    Identified an oncogenic role for POC1A, showing overexpression drives EMT, invasion, and metastasis via STAT3 signaling in triple-negative breast cancer.

    Evidence RNA-seq, in vitro migration/invasion assays, xenograft models, and STAT3 pathway inhibition

    PMID:40830747

    Open questions at the time
    • How a centriolar protein activates STAT3 mechanistically not defined
    • Relationship between centriole function and EMT-promoting activity unknown
    • Single lab; cancer-type generality untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how POC1A's core centriole-scaffolding role mechanistically connects to its context-specific functions in Golgi trafficking, insulin-receptor localization, and STAT3-driven EMT.
  • No unifying mechanism linking centriole/cilia function to metabolic and oncogenic phenotypes
  • No structure of the assembled inner scaffold
  • Regulation of POC1A incorporation and turnover during the cell cycle uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005929 cilium 2 GO:0005794 Golgi apparatus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1266738 Developmental Biology 1 R-HSA-1640170 Cell Cycle 1 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
FAM161AMDM1POC1BPOC5
Complex memberships
centriole inner scaffold (POC1A–POC1B–POC5–FAM161A–MDM1)

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 POC1A forms heterodimers with POC1B within the centriole lumen; the WD40 domain of POC1A resides in the centriole lumen and interacts with POC5, while the WD40 domain of POC1B localizes close to the centriole wall. This POC1A–POC1B heterodimer organizes an inner scaffold interaction network also involving FAM161A and MDM1, which bind POC1A–POC1B and likely position the POC5 tetramer near the centriole wall. POC1A–POC5 interaction and POC5 tetramerization are essential for inner scaffold formation and centriole stability. Interaction network mapping (Co-IP/pulldown), domain localization studies, genetic disruption of POC1A and POC1B (single and double deletion), structural/functional analysis of WD40 domain interactions Nature communications High 39543170
2012 POC1A and POC1B each independently localize to centrioles and spindle poles. A fraction of each protein is stably incorporated into parental centrioles. Depletion of both POC1A and POC1B (but not either alone) prevents incorporation into nascent centrioles, causing loss of centriole integrity and maturation, failure of centriole duplication, and generation of monopolar/unequal spindles. POC1B, but not POC1A, is phosphorylated during mitosis, and depletion of POC1B alone perturbs cell proliferation. Isoform-specific antibodies, RNAi depletion (single and double knockdown), live-cell imaging, immunofluorescence localization, FRAP-like incorporation assays Journal of cell science High 23015594
2012 Truncating mutations in POC1A cause defective ciliogenesis; siRNA knockdown of POC1A in fibroblast cells recapitulates the ciliogenesis defect. Patient-derived cells also show abnormal mitotic mechanics with multipolar spindles, consistent with a role for POC1A in both ciliogenesis and mitotic spindle integrity. siRNA knockdown in fibroblasts, immunofluorescence for cilia and spindle organization, patient cell analysis American journal of human genetics Medium 22840364
2012 A p.Leu171Pro missense mutation in POC1A causes abnormal centrosome number and distribution in patient cells, dispersed Golgi morphology, aberrant cholera-toxin trafficking from the plasma membrane to the Golgi, and accumulation of large cytosolic vesicles, demonstrating that POC1A is required for proper centrosome function and Golgi assembly/trafficking. Patient-derived cell analysis, immunofluorescence of centrosomes and Golgi, cholera-toxin trafficking assay American journal of human genetics Medium 22840363
2015 A p.T120A missense mutation in POC1A causes formation of supernumerary centrosomes and multipolar spindles with abnormal chromosome arrangement in patient fibroblasts. This mutation is accompanied by alterations in the centrosome-associated WD repeat protein p80-katanin, implicating POC1A in regulating centriole number and spindle assembly upstream of or alongside p80-katanin. Patient primary fibroblast culture, immunofluorescence for centrosomes and mitotic spindles, gene expression array, co-analysis of p80-katanin Human molecular genetics Medium 26162852
2015 Disruption of Poc1a in mice (by LINE-1-mediated insertion) causes impaired cilia formation and multipolar spindles in fibroblasts, defective spermatogenesis with progressive germ cell loss, and disorganized chondrocyte proliferative zone (chondrocytes fail to re-align after division and undergo increased apoptosis). Spermatogonial stem cell transplantation showed Poc1a is essential for both Sertoli cell and germ cell function. Mouse genetic model (spontaneous insertion mutant), cilia formation assay, spindle analysis, histology of growth plate, spermatogonial stem cell transplantation PLoS genetics High 26496357
2015 Patient cells with a frameshift mutation in POC1A exhibit increased centrosome amplification and multipolar spindle formation during mitosis, with normal DNA content (arguing against mitotic skipping or cell fusion). Centrosome clustering at mitotic spindles and in primary cilia partially mitigates centrosome amplification, and primary ciliary formation is normal in this specific mutation context. Patient-derived primary cell analysis, immunofluorescence for centrosomes, spindle, and primary cilia, DNA content analysis Journal of molecular endocrinology Medium 26336158
2024 Loss of POC1A protein expression in patient fibroblasts and POC1A-deleted human adipose stem cells impairs ciliogenesis and adipocyte differentiation, induces cellular senescence, and leads to resistance to insulin and IGF-1. An altered subcellular localization of insulin receptors (and to a lesser extent IGF-1 receptors) was also observed, potentially contributing to hormone resistance. Patient fibroblasts, CRISPR-deleted human adipose stem cells, ciliogenesis assay, adipocyte differentiation assay, cellular senescence assay, insulin/IGF-1 signaling assays, receptor localization by immunofluorescence European journal of endocrinology Medium 38245004
2025 POC1A promotes epithelial-mesenchymal transition (EMT) in triple-negative breast cancer cells, regulating invasion and metastasis in vitro and in vivo. RNA sequencing followed by experimental validation revealed that POC1A acts through activation of the STAT3 signaling pathway to induce EMT. RNA-seq pathway analysis, Western blot, RT-qPCR, immunofluorescence, migration/invasion assays, xenograft mouse models, STAT3 pathway inhibition/validation Molecular medicine (Cambridge, Mass.) Medium 40830747

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism. American journal of human genetics 74 22840364
2012 Poc1A and Poc1B act together in human cells to ensure centriole integrity. Journal of cell science 67 23015594
2012 Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis syndrome is caused by a POC1A mutation. American journal of human genetics 55 22840363
2015 Novel POC1A mutation in primordial dwarfism reveals new insights for centriole biogenesis. Human molecular genetics 26 26162852
2015 LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A) Causes Growth Insufficiency and Male Infertility in Mice. PLoS genetics 25 26496357
2015 Truncation of POC1A associated with short stature and extreme insulin resistance. Journal of molecular endocrinology 24 26336158
2016 SOFT syndrome caused by compound heterozygous mutations of POC1A and its skeletal manifestation. Journal of human genetics 18 26791357
2024 An interaction network of inner centriole proteins organised by POC1A-POC1B heterodimer crosslinks ensures centriolar integrity. Nature communications 15 39543170
2015 Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations. American journal of medical genetics. Part A 14 26374189
2017 A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10. European journal of endocrinology 12 28819016
2019 A novel POC1A variant in an alternatively spliced exon causes classic SOFT syndrome: clinical presentation of seven patients. Journal of human genetics 11 31767933
2024 Ciliopathy due to POC1A deficiency: clinical and metabolic features, and cellular modeling. European journal of endocrinology 6 38245004
2021 Identification of SOFT syndrome caused by a pathogenic homozygous splicing variant of POC1A: a case report. BMC medical genomics 6 34419044
2021 Further phenotypic features and two novel POC1A variants in a patient with SOFT syndrome: A case report. Molecular medicine reports 5 33955509
2023 Case Report: Identification of a rare nonsense mutation in the POC1A gene by NGS in a diabetes mellitus patient. Frontiers in genetics 4 37056285
2022 Pigmentary retinopathy with perivascular sparing in a SOFT syndrome patient with a novel homozygous splicing variant in POC1A gene. Ophthalmic genetics 3 35930384
2025 POC1A induces epithelial-mesenchymal transition to promote growth and metastasis through the STAT3 signaling pathway in triple-negative breast cancer. Molecular medicine (Cambridge, Mass.) 2 40830747
2025 Immunohistochemical expression of POC1A, NUF2, and Ki-67 in invasive ductal carcinoma of the breast. American journal of clinical pathology 2 41237374
2024 Analysis of the role of POC1A in the development and progression of hepatocellular carcinoma. Translational cancer research 2 39430849

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