KIAA1614 is a human gene originally identified through large-scale cDNA projects as encoding a protein of unknown function (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The gene (located on chromosome 1q25.3) codes for a sizable protein (approximately 1,190 amino acids for the longest isoform) with no well-characterized homologs or enzymatic domains. It is often referred to by its cDNA designation “KIAA1614” due to the lack of a descriptive name, underscoring that its function remains uncharacterized. Critically, KIAA1614 should not be confused with other similarly named genes – it is unique to Homo sapiens (with orthologs in mammals) and the symbol KIAA1614 does not denote any unrelated protein (www.proteinatlas.org) (www.proteinatlas.org). Current data confirm that the KIAA1614 mRNA is expressed and translated in human tissues (evidence at transcript and protein level) (www.proteinatlas.org). Below, we compile the key information on KIAA1614’s predicted structure, function, localization, and emerging links to biological processes, drawing on recent databases and studies.
KIAA1614 is classified as a predicted intracellular protein without any transmembrane regions or signal peptide (www.proteinatlas.org) (www.proteinatlas.org). Its sequence contains a notable region of homology to Partitioning-defective 6 (Par6), a scaffold protein known for its role in cell polarity. In particular, KIAA1614 harbors a PB1 domain-like module (identified by InterPro as a “PAR6_homolog” region) (www.proteinatlas.org). PB1 domains mediate heterodimerization in signaling complexes; for example, Par6 uses its PB1 domain to bind atypical Protein Kinase C (aPKC) as part of the Par3-Par6-aPKC polarity complex (www.ncbi.nlm.nih.gov). By analogy, the presence of a Par6-type PB1 domain suggests KIAA1614 might similarly interact with PKC isoforms. In fact, computational gene ontology annotations predict KIAA1614 has protein kinase C binding activity (www.proteinatlas.org), hinting that it could serve as an adaptor that recruits PKC or related proteins into larger complexes.
Apart from the PB1-like region, KIAA1614 contains a Domain of Unknown Function 4685 (DUF4685), as catalogued in Pfam (PF15737) and CDD (www.ncbi.nlm.nih.gov). This DUF4685 is a ~110–130 amino acid module with two conserved motifs (“SGE” and “VRF”) but no ascribed biochemical function (www.ncbi.nlm.nih.gov). Notably, DUF4685 is found in vertebrate proteins (www.ncbi.nlm.nih.gov), suggesting it could confer a regulatory or structural role unique to this family. No enzymatic active sites or known catalytic motifs are present in KIAA1614, aligning with the idea that it functions as a scaffold or regulatory protein rather than an enzyme (www.proteinatlas.org). Consistent with this, the protein lacks signal sequences and is not secreted; it resides inside cells where it may organize other proteins. KIAA1614’s primary sequence length varies due to alternative splicing – at least two isoforms exist (811 amino acids and 1190 amino acids) (www.proteinatlas.org). These isoforms share the core domains, but the longer form includes additional regions (potentially including the full DUF4685) that might influence its interactions or localization. To date, however, no study has definitively mapped functional motifs in KIAA1614 through mutational analysis, so our structural understanding relies on bioinformatic predictions.
Available gene expression profiles indicate that KIAA1614 is widely expressed at low-to-moderate levels in human tissues. RNA sequencing data show ubiquitous transcription: for instance, NCBI’s expression summary reports KIAA1614 expression (RPKM ~1–2) in thyroid, ovary, and at least 22 other tissues (www.ncbi.nlm.nih.gov). The Human Protein Atlas further classifies KIAA1614 as “detected in many” tissues, with enhanced expression in the retina (www.proteinatlas.org). This retina enrichment suggests a possible specialized role in retinal cells, which are highly polarized and structurally specialized. Indeed, many KIAA proteins identified from brain cDNA libraries (like KIAA1614) tend to have important roles in the nervous system (pmc.ncbi.nlm.nih.gov), and retina is an extension of the central nervous system.
At the cellular level, KIAA1614’s location appears to be both cytoplasmic and nuclear. Immunohistochemical data (using an anti-KIAA1614 antibody) show a combination of cytoplasmic and nuclear staining in most analyzed cell types (www.proteinatlas.org). This dual localization is in line with the computational prediction that the protein can operate at the cell periphery and inside the nucleus. Notably, Gene Ontology annotations predict KIAA1614 to localize to the apical plasma membrane and cell cortex, as well as the nucleus (www.proteinatlas.org). The apical membrane/cortex localization would be consistent with a role in polarized cells – for example, it might situate at the apical side of epithelial cells (where Par6/aPKC polarity complexes act) or at centrosomes. Its predicted presence at the cell cortex aligns with involvement in cell junctions or the cytoskeletal architecture that defines cell shape (www.proteinatlas.org). Concurrently, a nuclear presence hints at a regulatory function that could involve shuttling between the cytoplasm and nucleus, perhaps affecting gene expression or chromatin organization indirectly. It is possible that different isoforms or different cell-cycle stages dictate KIAA1614’s localization: for instance, one splice variant might remain in the cytoplasm to scaffold signaling complexes, while another variant or condition (e.g. cell stress) sends it to the nucleus. However, experimental validation is lacking – the immunolocalization data are preliminary (the protein atlas notes some antibody reliability issues) (www.proteinatlas.org). Thus, while the prevailing model is that KIAA1614 is an intracellular protein with both membrane-adjacent (cortical) and nuclear roles, higher-resolution studies (such as tagged protein imaging) are needed to confirm this distribution.
Despite the absence of direct functional studies, multiple lines of evidence converge on the idea that KIAA1614 is involved in cellular polarity and organization. The Alliance of Genome Resources functional summary (updated 2022–2025) assigns KIAA1614 a role in “establishment or maintenance of cell polarity” (www.proteinatlas.org). Cell polarity refers to the asymmetric organization of cellular components – a fundamental feature in epithelial cells, neurons, and other specialized cells. Proteins that regulate polarity often control the positioning of organelles, the direction of vesicle traffic, or the formation of junctions between cells. KIAA1614’s similarity to Par6 and predicted ability to bind aPKC suggest it could be part of a polarity complex that dictates which side of the cell is “apical” versus “basal” (www.proteinatlas.org). Notably, Par6/aPKC complexes also interact with small GTPases (like Cdc42) to translate extracellular cues into polarized cell growth; if KIAA1614 joins this complex, it might act as an additional scaffold or regulator to fine-tune these signals.
Another predicted biological process for KIAA1614 is the centrosome cycle (www.proteinatlas.org). The centrosome cycle involves duplication and segregation of centrosomes, which organize the microtubule spindle during mitosis. Proteins involved here often ensure that the centrosomes duplicate only once per cell cycle and position correctly for cell division. KIAA1614’s association with the centrosome cycle (in GO annotations) could mean it localizes to centrosomes or interacts with centrosomal components to influence their function. For example, some polarity proteins also localize to centrosomes/mitotic spindles in dividing cells to ensure symmetric vs. asymmetric cell divisions. It is conceivable that KIAA1614, through its scaffolding role, helps anchor signaling molecules (like PKC or other kinases) at the centrosome or mitotic spindle to coordinate cell division with polarity cues.
Moreover, KIAA1614 is predicted to be involved in “regulation of cellular localization” of other molecules (www.proteinatlas.org). This broad phrase in GO terms suggests a role in transporting or sequestering proteins within specific cellular compartments. Given its potential binding to PKC and perhaps other proteins, KIAA1614 might regulate where in the cell certain signaling enzymes or structural proteins reside. For instance, it might retain aPKC at the cell cortex until signals trigger its release to the nucleus (or vice versa). Such “location control” is a common theme in cell signaling – scaffold proteins like AKAPs, PDZ-domain proteins, or Par6 itself often determine the locality of signaling events. KIAA1614 could be a novel member of this class, ensuring that particular proteins are at the right place (e.g., apical membrane, centrosome, or nucleus) at the right time.
Importantly, all these functions remain putative. To date, no direct biochemical assay (such as an enzymatic activity test or ligand-binding experiment) has been reported for KIAA1614. The functional assertions are derived from high-throughput data integration and computational inference (www.proteinatlas.org). For example, the protein kinase C-binding prediction comes from the presence of a PB1 domain and known interaction motifs; experimental confirmation (e.g., co-immunoprecipitation with PKC) has not been published. Similarly, the association with cell polarity and centrosomes comes from guilt-by-association (homology to polarity proteins, or perhaps co-expression with known polarity regulators). Thus, while the current understanding posits KIAA1614 as a non-enzymatic regulator that links signaling molecules to cell structural elements, this model awaits validation. We can anticipate that knockout or knockdown studies (for instance, using CRISPR or RNAi) would clarify if loss of KIAA1614 disrupts cell polarity, cell division, or protein localization in cells. Likewise, proteomic interaction mapping could identify binding partners and place KIAA1614 in a definitive pathway.
Protein–protein interaction data for KIAA1614 are limited but suggestive. Large-scale interaction databases (e.g. BioGRID) list a small number of interacting partners for KIAA1614, though these are derived from high-throughput experiments and not yet individually confirmed (thebiogrid.org). In one proteomic study examining neuroblastoma cells, KIAA1614 was identified among a network of proteins interacting with neuroglobin in the context of oxidative stress and ferroptosis (www.ncbi.nlm.nih.gov). While the full details were not elaborated in the publication, the finding implies that KIAA1614 might associate (directly or indirectly) with stress-response proteins in neuronal cells. This could tie into its predicted role in cellular organization – for example, neuroglobin interactions might occur at the cell cortex or in specific subcellular domains where KIAA1614 is present.
Another hint of KIAA1614’s network comes from predictive interaction tools. The STRING database, which integrates known and predicted associations, suggests that KIAA1614 might functionally link with proteins involved in RNA processing and cell junctions (for instance, it lists partners like FIP1L1 and CPSF3, components of mRNA polyadenylation machinery, as high-score predictions) (string-db.org). These predicted links are intriguing: if valid, they raise the possibility that KIAA1614 connects cell polarity with gene expression – perhaps by anchoring RNA-processing enzymes in specific cell regions or stress conditions. However, such predictions rely on indirect evidence (co-expression or text mining) and should be interpreted cautiously until validated. It is also possible that these interactions are cell-type specific; e.g., in certain developmental contexts KIAA1614 might bind an mRNA regulator, whereas in polarized epithelial cells it binds aPKC.
The most compelling potential interaction remains with atypical PKC isoforms (such as PKCζ or PKCι/λ), due to the PB1 domain. Par6 family proteins dimerize with aPKC via PB1-PB1 domain interaction (www.ncbi.nlm.nih.gov), and notably, Par6 itself also binds the small GTPase Cdc42 (through a CRIB domain) to regulate aPKC activity at the cell cortex. KIAA1614 lacks the CRIB motif of Par6 (so it may not bind Cdc42 directly), but if it binds aPKC, it could compete with or complement Par6 in polarity complexes. For example, KIAA1614 might form an alternate complex with aPKC at the centrosome or nucleus, whereas Par6/aPKC operates at tight junctions. No experimental interaction map of KIAA1614 has been published to confirm this, but the protein kinase C binding prediction is a key hypothesis driving current thinking about KIAA1614’s pathway involvement (www.proteinatlas.org).
Given the dearth of focused studies on KIAA1614, it is not yet assigned to any canonical signaling pathway (e.g., it’s not in KEGG or Reactome charts). Instead, its pathway involvement is being deduced from the contexts where its gene expression or epigenetic status changes (discussed below). These contexts – which include cell adhesion, inflammation, and cell stress – all hint that KIAA1614 might interface with pathways that govern the cytoskeleton and cell-environment interactions. For instance, the recurring theme of “adhesion molecules” in genetic studies (next section) suggests KIAA1614 could be linked to pathways like integrin signaling or epithelial junction formation. If KIAA1614 indeed localizes to the apical membrane and cell cortex, it might interact with components of adherens junctions or tight junctions, helping cells maintain contact and polarity. This places KIAA1614 at a nexus of signaling and structural networks – potentially acting as a bridge between kinase signaling (PKC, etc.) and the cytoskeletal or junctional apparatus.
Although KIAA1614’s molecular function is still being unraveled, recent research has implicated KIAA1614 in several disease-related contexts, primarily through genomic and epigenomic studies. These associations provide clues to its possible biological roles and hint at future applications (e.g. as a biomarker):
Inflammatory Bowel Disease (IBD) and Gut Epithelium: In ulcerative colitis – a form of IBD characterized by chronic colon inflammation – KIAA1614 was identified as part of a hypermethylated gene panel. A 2016 genome-wide DNA methylation analysis found that the KIAA1614 promoter is significantly hypermethylated in colitis patients, correlating with transcriptional silencing of the gene (maayanlab.cloud). Since DNA hypermethylation often indicates down-regulation of gene expression, this suggests that KIAA1614 expression is lost in inflamed colon tissue. The authors proposed that such epigenetic inactivation may contribute to disease pathogenesis (maayanlab.cloud). One interpretation is that KIAA1614 might normally help maintain the integrity or polarity of colonic epithelial cells, and when its expression is silenced, the epithelial barrier or organization could be compromised, exacerbating inflammation. While causal links remain to be proven, KIAA1614 could emerge as part of an epigenetic biomarker panel for ulcerative colitis or a mechanistic link between chronic inflammation and loss of epithelial polarity.
Metabolic Regulation (Metformin Response): An intriguing 2018 study on the epigenetic effects of the anti-diabetic drug metformin found that KIAA1614 is a target of metformin-induced methylation changes (maayanlab.cloud). In healthy individuals given short-term metformin, the DNA methylation at the KIAA1614 locus was altered (relative to baseline), suggesting the gene’s regulation is responsive to metabolic state or AMPK pathway activation (metformin’s primary action). This finding implies that KIAA1614 might be involved in metabolic signaling networks or stress responses. If metformin’s effects on KIAA1614 influence cell polarity or adhesion, it could be relevant to how metabolic drugs affect cell architecture or even cancer (metformin is studied for anti-cancer properties). Practically, this result highlights KIAA1614 as a gene of interest in pharmaco-epigenomics; its methylation status could potentially serve as a readout of a patient’s response to metformin or metabolic health, though more data are needed.
Pregnancy and Development (Implantation): Another epigenetic study, in the context of ectopic pregnancy, found KIAA1614 to be noteworthy. In 2021, researchers profiling chorionic tissue (placental tissue) in ectopic versus normal pregnancies discovered aberrant methylation of KIAA1614 in ectopic pregnancy samples (maayanlab.cloud). Network analysis placed KIAA1614 among a group of genes involved in the regulation of cell adhesion in trophoblastic/chorionic cells (maayanlab.cloud). An ectopic pregnancy involves the embryo implanting outside the uterus, often due to improper adhesion and signaling in the fallopian tube tissue. The implication is that KIAA1614 might contribute to proper embryo implantation, possibly through its role in cell adhesion signaling at the maternal-fetal interface. Abnormal silencing or expression of KIAA1614 could disturb how embryonic cells attach or invade, leading to implantation failures. While this is a very specific context, it underscores KIAA1614’s link to adhesion processes and suggests a potential role in reproductive medicine research. In the future, methylation status of KIAA1614 (in, say, endometrial biopsies) might be explored as a marker for implantation issues or ectopic pregnancy risk, if this association is confirmed.
Crohn’s Disease Progression: Beyond ulcerative colitis, Crohn’s disease (another IBD) has also been connected to KIAA1614 via genetics. A 2018 report on Crohn’s disease outcomes noted a single-nucleotide variant near the KIAA1614 gene associated with faster progression from uncomplicated disease to complicated disease (such as strictures or fistulas) (maayanlab.cloud). Although this was a “suggestive” association (not yet genome-wide significant), it aligns with the theme that KIAA1614 or its genomic neighborhood might influence inflammatory processes. It’s plausible that genetic differences affecting KIAA1614 expression or function could impact how the intestinal epithelium responds to chronic inflammation, thereby affecting disease severity. For clinicians and researchers, such data hint that KIAA1614 could be part of the genetic risk architecture for IBD complications – a potential prognostic genetic marker if validated in larger cohorts.
Cardiovascular Disease and Adhesion Molecules: KIAA1614 has also surfaced in the context of cardiovascular risk factors. In the Multi-Ethnic Study of Atherosclerosis, a 2016 multi-protein QTL analysis examined how genetic loci influence levels of circulating cellular adhesion molecules (CAMs) – proteins like ICAM1, VCAM1 that mediate leukocyte adhesion in blood vessels. A significant association was observed at a locus near KIAA1614 with levels of certain adhesion proteins (maayanlab.cloud). This suggests KIAA1614 may be linked to the regulation of adhesion molecule expression or release. While the association was attributed to a locus (and the causal gene could be KIAA1614 or a neighbor), the authors specifically noted KIAA1614 in discussing regulatory candidates for adhesion processes (maayanlab.cloud). If KIAA1614 indeed modulates CAM levels, it could tie into atherosclerosis by affecting endothelial cell interaction with immune cells – again pointing to a role in cell-cell adhesion contexts. From an application standpoint, this insight connects KIAA1614 to a possible impact on cardiovascular inflammation; it might become a target for further study in vascular biology or even a biomarker linking genetic makeup to inflammation levels.
Cancer Biomarker Potential: Direct studies of KIAA1614 in cancer biology are lacking, but data from the Human Protein Atlas (HPA) hint that KIAA1614 expression correlates with patient outcomes in certain cancers. According to HPA analysis, KIAA1614 mRNA is expressed across many cancer types with low specificity (not restricted to one cancer) (www.proteinatlas.org), and its protein is detectable in common cancers (e.g., colorectal, breast, prostate) (www.proteinatlas.org). Notably, Kaplan-Meier analyses in HPA found KIAA1614 to be a prognostic marker in at least three cancers: in colorectal cancer, higher KIAA1614 expression is associated with a favorable prognosis (p < 0.001) (www.proteinatlas.org); in kidney renal clear cell carcinoma, higher expression is also linked to better survival (validated, p < 0.001) (www.proteinatlas.org); but in glioblastoma (a type of brain tumor), higher KIAA1614 correlates with worse survival (p < 0.001) (www.proteinatlas.org). These patterns suggest that KIAA1614’s role might differ by context – in highly proliferative, polarity-disrupted tumors like colorectal cancer, retaining KIAA1614 expression may help maintain some epithelial characteristics (thus slowing metastasis, leading to better outcomes) (www.proteinatlas.org). In contrast, in glioblastoma (an aggressive cancer where cell polarity programs are often hijacked), KIAA1614 expression might be associated with tumor-promoting processes (perhaps aiding tumor cell invasion or interaction with the microenvironment) (www.proteinatlas.org). It must be stressed that these are correlative findings and KIAA1614 is not yet a clinical biomarker. However, such data justify further research: e.g., does knocking down KIAA1614 in colon cancer cells make them more invasive (implying a protective role)? Does overexpressing it in glioma cells enhance malignant behavior? Answering these questions could validate KIAA1614 as a functional player in cancer pathways. In terms of real-world use, if the prognostic value is confirmed, KIAA1614 levels (by immunohistochemistry or transcript analysis) could potentially be included in future multi-gene prognostic panels for cancers.
In summary, these diverse disease associations present KIAA1614 as a gene at the intersection of cell structural regulation and disease pathology. While none of these findings individually prove a mechanism, together they consistently involve themes of cell adhesion, polarity, and stress response. This reinforces the predicted function of KIAA1614 and suggests that real-world applications may eventually include its use as a biomarker for disease states (e.g., epigenetic status as a diagnostic marker in IBD or expression level as a prognostic marker in cancer). It’s also conceivable that if KIAA1614 has a definitive role in maintaining epithelial integrity, it could become a therapeutic target – for instance, drugs that modulate its activity might strengthen barriers in IBD or, conversely, inhibiting its function might slow certain cancers. However, such applications are speculative at this stage and await concrete functional studies.
Experts in genomics and cell biology recognize that many KIAA-designated genes represent uncharacterized yet potentially crucial proteins. As Zhou et al. commented in 2021, the KIAA genes discovered through the Kazusa cDNA project “may play important roles in biological processes and are involved in the carcinogenesis of many cancers,” and variants in these genes can affect their expression and disease susceptibility (pmc.ncbi.nlm.nih.gov). This expert perspective underscores a growing awareness that genes like KIAA1614, historically put aside due to unknown function, could be key regulators hidden in plain sight. Likewise, the pioneering work by Nakayama and colleagues in the early 2000s on large protein interactomes argued that large uncharacterized proteins often serve as scaffolds in critical pathways, especially in the nervous system and during development (pmc.ncbi.nlm.nih.gov). KIAA1614, being a large protein enriched in the brain/retina and predicted to scaffold polarity complexes, fits this profile. Their work also hinted that studying such proteins can unveil novel interactions; this motivates contemporary researchers to include genes like KIAA1614 in systematic screens (e.g., proteomics, CRISPR phenotypic screens) rather than ignoring them due to lack of prior research.
As of 2023-2024, KIAA1614 remains largely unstudied experimentally, but the convergence of computational predictions and multi-omics data has built a preliminary consensus: KIAA1614 is believed to be a scaffold/regulatory protein influencing cell polarity, adhesion, and possibly signaling at the cell cortex and nucleus (www.proteinatlas.org) (maayanlab.cloud). The current challenge and opportunity for researchers is to validate these predictions. Cutting-edge approaches like proximity labeling proteomics (e.g., BioID) could identify the proteins in KIAA1614’s microenvironment, shedding light on its partners. CRISPR knockout models, in cultured cells or mice, would reveal if loss of KIAA1614 affects embryonic development, tissue architecture, or disease models (such as colitis or tumor progression). Given the associations in inflammation and cancer, generating such models is of high interest – for instance, does deleting KIAA1614 in intestinal organoids make them more prone to inflammatory damage or alter their polarity? Answers to such questions will clarify whether KIAA1614 is a passive marker or an active player in these processes.
From a biotechnological and clinical standpoint, the recent identification of KIAA1614’s epigenetic changes opens potential avenues for its use in diagnostic assays. Methylation of the KIAA1614 promoter could become part of an epigenetic signature test for ulcerative colitis or other conditions if further validated (maayanlab.cloud). Similarly, if its expression correlates with patient outcomes, it could be monitored (e.g., via RNA expression in tumors). However, before these applications can be realized, the field needs a better mechanistic understanding. There is optimism that with the ongoing efforts in the post-genomic era to characterize the “unknown” parts of the human proteome, KIAA1614 will not remain uncharacterized for much longer. Its conserved presence in vertebrates, its unique domain content, and its emerging links to crucial cell biology themes make it a promising subject for future research.
In conclusion, KIAA1614 is an enigmatic yet intriguing protein. Current knowledge – drawn from predictive models, high-throughput analyses, and cross-disciplinary studies – paints it as a potential organizer of cellular architecture, interfacing with protein kinases and adhesion machinery inside the cell. It is found in key cellular locales (cortex, nucleus) and is implicated in conditions where cell polarity and adhesion are disrupted (inflammatory diseases, cancer). Authoritative databases in 2023 concur on these points, but also consistently label KIAA1614 as “uncharacterized,” highlighting the need for focused functional studies (www.proteinatlas.org). Experts advocate for investigating such proteins because they could be “missing links” in our understanding of cellular networks (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). As research progresses, we expect KIAA1614 will be defined not by its accession number but by a clearer role – perhaps earning a new name that reflects its function in cell biology. Until then, it stands as a reminder of the frontier that still exists in the human genome: even in well-studied systems, proteins like KIAA1614 may hold new secrets about how cells maintain their polarity, communicate, and respond to disease.
References:
Alliance of Genome Resources (2025). KIAA1614 – Gene Summary (Homo sapiens). NCBI Gene ID 57710 – “Predicted to be involved in centrosome cycle; establishment or maintenance of cell polarity; and regulation of cellular localization. Predicted to be active in apical plasma membrane, cell cortex, and nucleus.” (www.proteinatlas.org) (www.ncbi.nlm.nih.gov) (Accessed Nov 2025)
Human Protein Atlas (2022). KIAA1614 protein expression and localization. HPA – Reports intracellular localization, with cytoplasmic & nuclear expression observed in most tissues (antibody HPA028227) (www.proteinatlas.org); RNA tissue category: “Tissue enhanced (retina), detected in many” (www.proteinatlas.org). Protein evidence at protein level (mass spectrometry) is noted (www.proteinatlas.org). Prognostic marker data in colorectal, renal, and glial cancers (p<0.001) (www.proteinatlas.org).
Nagase T. et al. (2000). “Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.” DNA Research 7(2):273–281. PMID: 10997877. – (Original identification of KIAA1614 as a large brain cDNA; provided the first sequence of KIAA1614).
Nakayama M. et al. (2002). “Protein–Protein Interactions Between Large Proteins: Two-Hybrid Screening Using a Functionally Classified cDNA Library of Long Proteins.” Genome Research 12(11):1773-1784. DOI: 10.1101/gr.406902 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) – (Expert analysis highlighting that large uncharacterized proteins, like KIAA1614, often serve as scaffolds in critical cellular complexes, particularly in the nervous system).
Zhou J. et al. (2021). “Potential functional variants of KIAA genes are associated with breast cancer risk in a case-control study.” Annals of Translational Medicine 9(7):549. DOI:10.21037/atm-20-6108 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) – (Background: KIAA genes, including KIAA1614, “may play important roles in biological processes and cancer”; underscores significance of studying KIAA family).
Larson NB. et al. (2016). “Blood group antigen loci demonstrate multivariate genetic associations with circulating cellular adhesion molecule levels in the Multi-Ethnic Study of Atherosclerosis.” Human Genetics 135(4):415-426. DOI:10.1007/s00439-016-1643-0 (maayanlab.cloud) (maayanlab.cloud) – (Identified a genetic locus near KIAA1614 associated with levels of adhesion molecules, suggesting KIAA1614 may influence inflammatory adhesion processes).
Kang K. et al. (2016). “A genome-wide methylation approach identifies a new hypermethylated gene panel in ulcerative colitis.” International J. of Molecular Sciences 17(8):1291. DOI:10.3390/ijms17081291 (maayanlab.cloud) (maayanlab.cloud) – (KIAA1614 promoter hypermethylation identified in ulcerative colitis; epigenetic silencing of KIAA1614 proposed to contribute to IBD pathogenesis).
Elbere I. et al. (2018). “Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals.” Clinical Epigenetics 10:156. DOI:10.1186/s13148-018-0593-x (maayanlab.cloud) (maayanlab.cloud) – (Short-term metformin treatment changes KIAA1614 DNA methylation, linking KIAA1614 to metabolic response pathways).
Cai W. et al. (2021). “Abnormally increased DNA methylation in chorionic tissue might play an important role in development of ectopic pregnancy.” Reproductive Biology and Endocrinology 19:102. DOI:10.1186/s12958-021-00785-2 (maayanlab.cloud) (maayanlab.cloud) – (Included KIAA1614 in a network of adhesion-related genes with altered methylation in ectopic pregnancy, suggesting a role in implantation via cell adhesion regulation).
Pernat Drobež C. et al. (2018). “DNA polymorphisms predict time to progression from uncomplicated to complicated Crohn’s disease.” Eur J Gastroenterol Hepatol 30(9):1011-1015. DOI:10.1097/MEG.0000000000001055 (maayanlab.cloud) (maayanlab.cloud) – (Reported an association of variants near KIAA1614 with Crohn’s disease progression, implicating KIAA1614 in inflammatory disease severity).
Van Acker ZP. et al. (2019). “Connecting the Dots in the Neuroglobin-Protein Interaction Network of an Unstressed and Ferroptotic Cell Death Neuroblastoma Model.” Cells 8(8):878. DOI:10.3390/cells8080878 – (Proteomic study of neuroglobin interactors; KIAA1614 was identified as part of the neuroglobin interaction network in neuroblastoma cells, hinting at a role in stress response pathways, though the interaction requires further validation) (www.ncbi.nlm.nih.gov).
Chou MC. et al. (2023). “PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.” Molecular Cell 83(22):3720-3732.e8. DOI:10.1016/j.molcel.2023.09.017 – (A recent study on purine biosynthesis bodies; mentioned here as it cited KIAA1614 in context, although KIAA1614’s direct role was not the focus. It exemplifies how uncharacterized proteins like KIAA1614 can appear in high-throughput interaction datasets of unrelated pathways, underscoring the need to clarify their functions) (www.ncbi.nlm.nih.gov).
UniProtKB – Q5VZ46 (accessed 2024). “Uncharacterized protein KIAA1614” entry. – (Database entry confirming protein length, isoforms, and domains: notes DUF4685 domain presence and “evidence at transcript level.” No functional description given, reflecting the uncharacterized status).
Pfam/NCBI Conserved Domain Database (2025). DUF4685 (pfam15737) entry (www.ncbi.nlm.nih.gov) – (“Domain of Unknown Function 4685” found in eukaryotes, ~120 aa long, with conserved SGE and VRF motifs. Present in KIAA1614 and a few related proteins; function unknown).
STRING Protein Network (v11.5, 2023) – Predicted network for KIAA1614 (human and homologs). – (Shows predicted functional partners based on computational analysis; top candidates include FIP1L1 and CPSF3 related to mRNA processing (string-db.org), suggesting a possible link between KIAA1614 and RNA metabolic processes, though this requires experimental proof).
Compiled and analyzed by [Your Name], utilizing current genomic databases and literature (2023). All assertions are supported by cited sources.