The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Human PDZD7 encodes PDZ domain-containing protein 7 (alias PDZK7), a non-enzymatic, intracellular scaffold whose best-established function is to organize the transient USH2 ankle-link complex at the base of developing cochlear hair-cell stereocilia. Through multivalent PDZ-mediated interactions, PDZD7 helps assemble and position USH2A/usherin, ADGRV1/GPR98 and WHRN/whirlin, connecting membrane adhesion proteins to a larger cytoskeletal/transport network. This preserves stereociliary-bundle architecture required for normal cochlear mechanoelectrical transduction. Recent work further indicates that the complex assembles as a biomolecular condensate by liquid–liquid phase separation (LLPS). PDZD7 is therefore an adaptor/scaffold, not an enzyme, receptor, ion channel or transporter; it has no catalytic reaction or transported substrate (grati2012localizationofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 1-2, wang2023temporalandspatial pages 8-11).
The cochlear function is supported strongly by localization, biochemistry and knockout-mouse experiments. Human genetics supports an ultra-rare association with recessive nonsyndromic sensorineural hearing loss, but the number of independently informative families is small. Claims that heterozygous PDZD7 variants cause digenic Usher syndrome or modify retinal disease are plausible but remain less secure. PDZD7 should consequently not be represented as an ordinary, fully established primary Usher-syndrome gene without qualification (delmaghani2022thegeneticand pages 11-12, delmaghani2022thegeneticand pages 12-14).
The target is correctly identified as Homo sapiens PDZD7, approved name PDZ domain containing 7, corresponding to UniProt Q9H5P4 and alias PDZK7. The literature describes the same protein as a paralog of the Usher-network scaffolds harmonin/USH1C and whirlin/WHRN. Its reported multi-PDZ architecture, including three PDZ domains in the long form and a central proline-rich region, agrees with the supplied UniProt/InterPro annotations—PDZ (IPR001478/PF00595), PDZ superfamily (IPR036034), PDZD7_HN-like and USH2-complex protein (grati2012localizationofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 1-2).
No conflicting human or non-human protein with a deceptively similar symbol was substituted in this report. Animal Pdzd7 studies are used only as orthologous functional evidence for human Q9H5P4.
PDZ domains recognize short partner motifs, commonly C-terminal PDZ-binding motifs, and allow scaffolds to concentrate several proteins at a defined membrane-associated site. The long PDZD7 architecture—three PDZ domains plus a proline-rich region—therefore predicts an adaptor capable of multivalent interactions rather than catalysis. Structural similarity to harmonin and whirlin reinforces this interpretation (grati2012localizationofpdzd7 pages 1-2).
Isoform biology is incompletely resolved and likely tissue- and development-dependent. Mouse adult retina yielded five transcripts predicted to terminate after PDZ2 but before PDZ3, whereas developing cochlea expressed N-terminal products and rarer full-length transcripts. An approximately 120-kDa species was detected most consistently in developing cochlea around P5–P9 and retina at P6, but not reliably in adult tissues. These data suggest relatively low, developmentally regulated expression and caution against treating every transcript as functionally equivalent (zou2014deletionofpdzd7 pages 6-7).
Developing auditory hair cells bear actin-filled stereocilia arranged into a mechanically coherent bundle. Transient ankle links connect adjacent stereocilia near their bases. PDZD7 colocalizes there with:
Immunofluorescence and tagged-protein studies placed PDZD7 immediately above the tapered stereociliary base, peripheral to the actin core. It overlaps USH2A, ADGRV1 and WHRN but is distinct from the upper tip-link insertion site where MYO7A clusters. Stereocilia proteomics detected PDZD7 at abundance comparable to GPR98 in chick bundles (grati2012localizationofpdzd7 pages 1-2).
The four proteins form a dynamic, interdependent complex rather than a simple linear pathway. PDZD7 loss disrupts or redistributes USH2A, ADGRV1 and WHRN in developing cochlear hair cells. Conversely, PDZD7 becomes distributed abnormally along stereocilia in Ush2a- or Adgrv1-null mice, indicating that the membrane proteins help restrict the scaffold to the ankle region. WHRN and PDZD7 act synergistically: in P4 double-mutant hair cells, usherin was absent from inner-hair-cell bundles and barely detectable in outer-hair-cell bundles (zou2014deletionofpdzd7 pages 12-12, zou2014deletionofpdzd7 pages 10-12, zou2017therolesof pages 8-9).
Direct or complex-mediated PDZD7–WHRN association is supported by reciprocal co-immunoprecipitation. Cytoplasmic domains of USH2A and ADGRV1 also associated with PDZD7-containing complexes in early cell assays. More recent fragment-resolved biochemistry refined this model: the short USH2A cytoplasmic region bound PDZD7 PDZ1 with an approximate dissociation constant of 66 μM and tandem PDZ1–2 with 15 μM affinity. No direct interaction was detected between the tested ADGRV1 cytoplasmic tail and PDZD7 PDZ1–2 or PDZ3 by ITC or GST pull-down, suggesting that some earlier ADGRV1–PDZD7 association was bridged by USH2A, WHRN or complex avidity rather than a simple binary interaction (zou2014deletionofpdzd7 pages 10-12, wang2023temporalandspatial pages 2-3).
PDZD7 also associates with MYO7A in FLAG pull-down assays. Genetic experiments indicate that MYO7A is required for normal USH2-complex assembly, whereas SANS/USH1G is not required to position PDZD7 at ankle links. MYO7A may transport or anchor the assembly, although those alternatives have not been conclusively separated in vivo (zou2014deletionofpdzd7 pages 12-12, zou2017therolesof pages 1-1).
Older pull-down work additionally recovered SANS and approximately fourfold more harmonin from retinal lysate with GST-PDZD7 than with GST alone. These findings place PDZD7 in the broader Usher interactome, but do not establish that every interaction occurs simultaneously or directly in native hair cells (schneider2009homozygousdisruptionof pages 6-8).
PDZD7 functions principally at the cytoplasmic face of the stereociliary ankle-link region in developing inner-ear sensory hair cells. It is detectable at cochlear inner- and outer-hair-cell bundle bases from approximately P0–P10 in mice; the broader ankle-link complex is present mainly around P2–P12. PDZD7 and USH2A can be detected by embryonic day 18, before morphologically evident ankle links, implying that molecular recruitment precedes mature link formation (zou2014deletionofpdzd7 pages 6-7, zou2014deletionofpdzd7 pages 12-12, zou2015individualush2proteins pages 2-2).
Its precise biological process is hair-bundle morphogenesis and stabilization, upstream of fully effective auditory mechanotransduction. PDZD7 is not itself established as the force-gated transduction channel. Instead, loss of the ankle-link scaffold produces malformed bundles and secondary reductions in transduction currents and sensitivity. Thus, its relationship to signaling is structural: PDZD7 preserves the geometry and protein organization required for sound-induced bundle deflection to activate the mechanotransduction apparatus (zou2014deletionofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 6-7).
The most important recent functional advance is the 2023 Nature Communications study by Wang et al., published March 2023 (DOI 10.1038/s41467-023-37267-5). Purified-protein imaging, co-sedimentation, SEC-MALS, pull-down and cochlear-explant experiments supported a model in which multivalent WHRN–USH2A interactions initiate LLPS and recruit PDZD7 and ADGRV1 into an ankle-link condensate. At sufficiently high concentration, the ADGRV1 cytoplasmic tail inhibited phase separation, providing a possible mechanism for developmental disassembly of the transient links (wang2023temporalandspatial pages 1-2, wang2023temporalandspatial pages 2-3).
The deafness-associated PDZD7 G103R substitution is especially informative. G103 lies in the PDZ1 ligand-binding groove. G103R abolished or markedly impaired USH2A binding, prevented efficient PDZD7 recovery in the quaternary complex and excluded the mutant protein from phase-separated droplets. By contrast, G228R and M285R did not disrupt the tested PDZD7–USH2A interaction. This supplies a variant-to-interface-to-condensate mechanism: loss of one interaction lowers network multivalency and prevents proper local assembly (wang2023temporalandspatial pages 8-11, wang2023temporalandspatial pages 11-12).
This LLPS model is supported strongly in vitro and ex vivo, but its material properties and physiological concentrations have not yet been measured in living human cochlear hair cells. “Condensate” should therefore be regarded as a mechanistic model with substantial experimental support, not as a completed quantitative description of the native structure.
Constitutive Pdzd7-null mice show congenital profound deafness by auditory brainstem response, with abnormal distortion-product otoacoustic emissions and cochlear microphonics. Mature outer-hair-cell bundles exhibit separated, twisted and variably sized stereocilia, missing short-row stereocilia and eventual bundle collapse. Outer-hair-cell mechanotransduction currents and sensitivity are reduced; inner and vestibular hair cells are less severely affected, and overt vestibular behavior is relatively normal (zou2014deletionofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 6-7).
These experiments make two points. First, PDZD7 is causally required for auditory function rather than merely co-localizing with the ankle-link complex. Second, the primary defect is developmental bundle organization, with impaired mechanotransduction arising from loss of structural integrity and correct complex localization.
A genetic-interaction experiment found that Pdzd7/Whrn double mutants had ABR thresholds broadly similar to Pdzd7 nulls from 4–45 kHz, except at 11.3 kHz, where the double-mutant threshold was approximately 10% higher; DPOAE thresholds were indistinguishable over 8–32 kHz. This suggests substantial pathway overlap rather than fully additive physiological functions. Sample sizes for some localization comparisons were only two or three pups, limiting fine quantitative conclusions (zou2017therolesof pages 8-9).
PDZD7 has been reported at the base of the photoreceptor connecting cilium/periciliary region, consistent with membership in the retinal Usher interactome. Zebrafish knockdown caused photoreceptor death and reduced ADGRV1 localization, supporting a possible retinal role (grati2012localizationofpdzd7 pages 1-2, delmaghani2022thegeneticand pages 12-14).
Nevertheless, stable mouse loss-of-function gives a more qualified picture. In young Pdzd7-null mice, USH2A, ADGRV1 and WHRN retained grossly normal periciliary localization, and rod and cone electroretinograms were normal at one month. PDZD7 therefore appears less essential for gross USH2-complex positioning in mouse photoreceptors than in cochlear hair cells. Species differences, knockdown artifacts, age-dependent retinal degeneration and isoform redundancy remain possible explanations (zou2014deletionofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 10-12).
The defensible annotation is that PDZD7 is ciliary/periciliary-associated and potentially modulatory in retina, but autonomous human retinal disease from biallelic PDZD7 loss is not established as securely as its auditory function.
The original 2009 report, published February 2009 in Human Molecular Genetics (DOI 10.1093/hmg/ddn395), described one consanguineous family. A hearing-impaired boy was homozygous for a reciprocal t(10;11) translocation whose chromosome-10 breakpoint lay in PDZD7 intron 10; both parents and four unaffected siblings were heterozygous. The rearrangement disrupted the coding region of one transcript and 5′ UTR of another. At age eight, the child had congenital sensorineural hearing impairment without recognized retinitis pigmentosa or vestibular dysfunction (schneider2009homozygousdisruptionof pages 1-2, schneider2009homozygousdisruptionof pages 8-8).
This is persuasive segregation evidence, but not definitive by modern gene-validity standards: it is one family, only selected transcripts were disrupted, the rearrangement had a second chromosomal breakpoint, and later retinal manifestations could not be excluded. Subsequent reports have associated biallelic PDZD7 variants with mild-to-severe recessive nonsyndromic hearing loss, sometimes with normal retinal and vestibular examinations, but the aggregate case count remains small (schneider2009homozygousdisruptionof pages 6-8, delmaghani2022thegeneticand pages 11-12).
Open Targets currently links PDZD7/ENSG00000186862 to hearing-loss disorders and nonsyndromic genetic hearing loss, with three underlying association entries in the retrieved record. This database aggregation supports clinical relevance but does not replace case-level gene curation (OpenTargets Search: hearing loss,Usher syndrome-PDZD7).
Several individuals with biallelic USH2A variants plus a heterozygous PDZD7 variant reportedly had altered retinal severity, leading to designation of PDZD7 as an USH2 phenotype modifier. Another reported genotype combined monoallelic loss-of-function variants in ADGRV1 and PDZD7, suggesting digenic inheritance. However, patient numbers were very small and phenotypes variable. Moreover, young mice doubly heterozygous for Pdzd7 and Ush2a, Adgrv1, Whrn or Sans did not show increased congenital ABR thresholds. Authoritative review therefore places PDZD7 among ultra-rare or proposed Usher-related genes rather than the canonical set (zou2014deletionofpdzd7 pages 12-12, delmaghani2022thegeneticand pages 11-12, delmaghani2022thegeneticand pages 12-14).
Accordingly, the modifier/digenic model is biologically coherent—because all proteins occupy the same multivalent complex—but remains low-to-moderate-confidence clinical genetics, not settled Mendelian causality.
Nouri et al., published July 2024 in BMC Medical Genomics (DOI 10.1186/s12920-024-01942-3), studied one Iranian family with three affected sisters. All had congenital bilateral moderate-to-severe hearing loss plus achromatopsia/cone-dystrophy features. They were homozygous for PDZD7 c.251T>C (p.Ile84Thr) and a novel PDE6C c.1644G>A (p.Trp548Ter) stop variant; both parents and a healthy brother were heterozygous. The variants were in cis, approximately 8.3 cM apart. The authors classified PDZD7 p.Ile84Thr as likely pathogenic and PDE6C p.Trp548Ter as pathogenic (nouri2024clinicalcharacterizationsand pages 5-6).
The parsimonious interpretation is two linked recessive disorders—PDZD7-associated hearing loss and PDE6C-associated cone disease—not PDZD7-associated deaf-blindness. Yet because no recombinant individual separated the genotypes, this family does not independently prove the phenotypic assignment. The absence of ERG data and reliance on a single family are additional limitations (nouri2024clinicalcharacterizationsand pages 5-6).
PDZD7 currently has diagnostic and interpretive, rather than therapeutic, applications:
| Topic | Current annotation | Key evidence/model | Confidence/limitation |
|---|---|---|---|
| Identity and architecture | Human PDZD7 (alias PDZK7), corresponding to UniProt Q9H5P4, is a non-enzymatic, multi-PDZ-domain protein related to harmonin/USH1C and whirlin/WHRN. The long form has three PDZ domains and a central proline-rich region; shorter transcripts terminate before PDZ3. | Sequence and domain comparisons identify PDZD7 as an Usher-network scaffold. Mouse retina contained five splice variants predicted to terminate after PDZ2, whereas developing cochlea expressed N-terminal and rarer full-length transcripts (grati2012localizationofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 6-7, schneider2009homozygousdisruptionof pages 1-2). | High for identity and general architecture. The abundance and tissue distribution of individual human isoforms remain incompletely resolved. |
| Primary molecular role | Multivalent structural adaptor and scaffold, not an enzyme or transporter. PDZD7 organizes the USH2 ankle-link complex and links membrane proteins to other scaffolds or cytoskeletal machinery, supporting stereociliary-bundle development and mechanosensory function. | Pdzd7 loss disrupts localization of USH2A, ADGRV1 and WHRN in cochlear hair cells; reciprocal co-immunoprecipitation and pull-down assays support partner association (zou2014deletionofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 12-12, zou2014deletionofpdzd7 pages 10-12). | High in developing mouse cochlear hair cells. Not every reported interaction has been demonstrated to be direct in vivo. |
| Localization and developmental window | PDZD7 concentrates immediately above the tapered base of developing hair-cell stereocilia, peripheral to the actin core, at the ankle-link region; it is distinct from upper tip-link insertion sites. | Immunofluorescence, tagged-protein expression and stereocilia proteomics showed overlap with USH2A, ADGRV1 and WHRN. Mouse PDZD7 was detected at bundle bases from about P0–P10; the broader ankle-link complex is transiently present around P2–P12 (grati2012localizationofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 6-7, zou2015individualush2proteins pages 2-2). | High for rodent and chick developmental hair cells. Direct localization of endogenous PDZD7 in living human cochlear hair cells is unavailable. |
| USH2A interaction | PDZD7 tandem PDZ1–2 binds the short cytoplasmic tail of USH2A and helps recruit PDZD7 into the quaternary ankle-link assembly. | ITC measured approximate dissociation constants of 66 μM for PDZ1 and 15 μM for PDZ1–2 binding to a monomeric USH2A fragment. USH2A dimerization promoted incorporation into a complex with WHRN and ADGRV1 (wang2023temporalandspatial pages 2-3). | High for purified-protein binding. Measurements using isolated fragments may not reproduce membrane-localized avidity in cells. |
| ADGRV1 interaction | ADGRV1 is a membrane component of the same complex, but 2023 assays found no detectable direct binding of its cytoplasmic tail to PDZD7 PDZ1–2 or PDZ3; recruitment may occur indirectly through USH2A–WHRN multivalency. | ITC and GST pull-down were negative for the tested direct interaction, despite earlier cellular evidence that PDZD7 and ADGRV1 coexist and are mutually important for ankle-region localization (grati2012localizationofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 10-12, wang2023temporalandspatial pages 2-3). | Moderate mechanistic confidence. Earlier apparent associations may reflect different constructs or bridging proteins; the current model favors complex-level coupling. |
| WHRN and MYO7A interactions | PDZD7 hetero-associates with WHRN, while MYO7A may transport or anchor PDZD7-containing USH2 assemblies at stereocilia. | Reciprocal PDZD7–WHRN co-immunoprecipitation and genetic synergy support scaffold cooperation. FLAG pull-down identified MYO7A–PDZD7 association; Myo7a mutant analysis indicated that MYO7A is required for ankle-link-complex assembly (zou2014deletionofpdzd7 pages 10-12, zou2017therolesof pages 8-9, zou2017therolesof pages 1-1). | High for WHRN complex association; moderate for direct physiological MYO7A binding and the proposed transport-versus-anchoring mechanism. |
| 2023 liquid–liquid phase separation | PDZD7 contributes multivalency to an ankle-link biomolecular condensate. WHRN–USH2A interactions initiate condensation and recruit PDZD7 and ADGRV1; high ADGRV1-tail concentration can inhibit phase separation, suggesting a mechanism for temporal disassembly. | Purified-protein droplet imaging, co-sedimentation, SEC-MALS, pull-downs and cochlear-explant experiments supported LLPS-dependent assembly. Deafness-associated PDZD7 G103R in the PDZ1 binding groove abolished USH2A association and excluded PDZD7 from droplets; G228R and M285R did not disrupt that tested interaction (wang2023temporalandspatial pages 8-11, wang2023temporalandspatial pages 11-12, wang2023temporalandspatial pages 1-2, wang2023temporalandspatial pages 2-3). | Strong biochemical and ex-vivo evidence. Physiological concentrations, material state and condensate dynamics in intact human hair cells remain unmeasured. |
| Mouse loss-of-function phenotype | Pdzd7 deletion causes congenital profound hearing loss, outer-hair-cell bundle disorganization and degeneration, and reduced cochlear mechanotransduction and sensitivity, while gross vestibular behavior is comparatively preserved. | ABR, DPOAE, cochlear-microphonic, electrophysiological and ultrastructural analyses showed separated, twisted or missing stereocilia and bundle collapse. Inner and vestibular hair cells retained better structural and MET function than outer hair cells (zou2014deletionofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 6-7). | High for a causal auditory role in mice. Phenotypic severity and isoform dependence may differ between mouse alleles and human variants. |
| Retina and ciliary region | PDZD7 has been reported near the photoreceptor connecting-cilium base or periciliary region and is plausibly part of the retinal Usher interactome, but its autonomous retinal requirement is less secure than its cochlear role. | In Pdzd7-null mice, USH2A, ADGRV1 and WHRN retained gross periciliary localization and one-month rod and cone ERGs were normal. Zebrafish knockdown produced photoreceptor degeneration but may not model stable null alleles (grati2012localizationofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 10-12, delmaghani2022thegeneticand pages 12-14). | Moderate to uncertain. Species, developmental-stage and knockdown-versus-knockout differences preclude concluding that biallelic PDZD7 routinely causes human retinal disease. |
| Human genetics: 2009 disruption | Initial evidence linked biallelic PDZD7 disruption to congenital nonsyndromic sensorineural hearing impairment. | In one consanguineous family, an affected boy was homozygous for a reciprocal t(10;11) translocation disrupting PDZD7 intron 10; both parents and four unaffected siblings were heterozygous. At age eight, the child had no reported retinal or vestibular disease (schneider2009homozygousdisruptionof pages 6-8, schneider2009homozygousdisruptionof pages 1-2, schneider2009homozygousdisruptionof pages 8-8). | Suggestive but limited because this was one family with a transcript-specific structural disruption and a second chromosomal breakpoint. Later-onset retinal disease could not be excluded. |
| Human genetics: modifier and digenic model | Heterozygous PDZD7 variants have been proposed to modify retinal severity in biallelic USH2A disease or contribute with monoallelic ADGRV1 to digenic USH2. PDZD7 is best regarded as an ultra-rare hearing-loss gene and possible USH modifier, rather than a canonical confirmed USH locus. | Reports describe USH2A-plus-PDZD7 and ADGRV1-plus-PDZD7 genotypes with variable retinal severity. Young digenic mouse cohorts did not show elevated congenital ABR thresholds, weakening a simple two-locus model (zou2014deletionofpdzd7 pages 12-12, delmaghani2022thegeneticand pages 11-12, delmaghani2022thegeneticand pages 12-14). | Low to moderate for modifier or digenic causality because human numbers are very small, phenotypes vary and animal evidence is not fully concordant. |
| Human genetics: 2024 family | PDZD7 c.251T>C (p.Ile84Thr) was reported as likely pathogenic for hearing loss in a family also segregating a separate retinal-disease allele. | Three sisters had congenital bilateral moderate-to-severe hearing loss and achromatopsia or cone-dystrophy features. All were homozygous for PDZD7 p.Ile84Thr and PDE6C p.Trp548Ter; both parents and an unaffected brother were heterozygous. The variants were in cis and approximately 8.3 cM apart (nouri2024clinicalcharacterizationsand pages 5-6). | Supportive but not independently decisive for PDZD7 because no genotype separated the two conditions; limitations include one family, co-inheritance with homozygous PDE6C loss and absent ERG data. |
| Overall functional annotation | PDZD7 is principally a developmental stereociliary ankle-link scaffold and condensate component that organizes the USH2A–ADGRV1–WHRN network, preserving hair-bundle architecture needed for normal cochlear mechanotransduction. | Concordant localization, biochemical interaction, LLPS, mouse-knockout and rare human genetic evidence support this annotation (grati2012localizationofpdzd7 pages 1-2, zou2014deletionofpdzd7 pages 1-2, wang2023temporalandspatial pages 8-11, schneider2009homozygousdisruptionof pages 1-2). | High for the core cochlear scaffold function; moderate or lower for autonomous retinal disease, universal direct-partner assignments and human digenic or modifier interpretations. |
Table: Compact evidence map for human PDZD7/Q9H5P4, integrating molecular architecture, ankle-link function, phase separation, localization, animal models and human genetics. Confidence statements distinguish direct mechanistic evidence from unresolved clinical or cross-species inference.
Recommended primary annotation:
PDZD7 is a multi-PDZ-domain cytoplasmic scaffold that localizes to the ankle-link region at the base of developing cochlear hair-cell stereocilia. It promotes multivalent assembly and spatial restriction of the USH2A–ADGRV1–WHRN complex, including formation of an LLPS-dependent ankle-link condensate, thereby maintaining stereociliary-bundle architecture required for normal cochlear mechanotransduction.
Evidence confidence: high for cochlear developmental scaffolding and hearing function; moderate for individual direct-partner assignments in vivo; moderate-to-low for an essential retinal role; and low-to-moderate for human digenic or modifier interpretations.
References
(grati2012localizationofpdzd7 pages 1-2): M'hamed Grati, Jung-Bum Shin, Michael D. Weston, James Green, Manzoor A. Bhat, Peter G. Gillespie, and Bechara Kachar. Localization of pdzd7 to the stereocilia ankle-link associates this scaffolding protein with the usher syndrome protein network. The Journal of Neuroscience, 32:14288-14293, Oct 2012. URL: https://doi.org/10.1523/jneurosci.3071-12.2012, doi:10.1523/jneurosci.3071-12.2012. This article has 81 citations.
(zou2014deletionofpdzd7 pages 1-2): Junhuang Zou, Tihua Zheng, Chongyu Ren, Charles Askew, Xiao-Ping Liu, Bifeng Pan, Jeffrey R. Holt, Yong Wang, and Jun Yang. Deletion of pdzd7 disrupts the usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice. Human molecular genetics, 23 9:2374-90, May 2014. URL: https://doi.org/10.1093/hmg/ddt629, doi:10.1093/hmg/ddt629. This article has 78 citations and is from a domain leading peer-reviewed journal.
(wang2023temporalandspatial pages 8-11): Huang Wang, Haibo Du, Rui Ren, Tingting Du, Lin Lin, Zhe Feng, Dange Zhao, Xiaoxi Wei, Xiaoyan Zhai, Hongyang Wang, Tingting Dong, Jin-Peng Sun, Hao Wu, Zhigang Xu, and Qing Lu. Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation. Nature Communications, Mar 2023. URL: https://doi.org/10.1038/s41467-023-37267-5, doi:10.1038/s41467-023-37267-5. This article has 17 citations and is from a highest quality peer-reviewed journal.
(delmaghani2022thegeneticand pages 11-12): Sedigheh Delmaghani and Aziz El-Amraoui. The genetic and phenotypic landscapes of usher syndrome: from disease mechanisms to a new classification. Human Genetics, 141:709-735, Mar 2022. URL: https://doi.org/10.1007/s00439-022-02448-7, doi:10.1007/s00439-022-02448-7. This article has 170 citations and is from a peer-reviewed journal.
(delmaghani2022thegeneticand pages 12-14): Sedigheh Delmaghani and Aziz El-Amraoui. The genetic and phenotypic landscapes of usher syndrome: from disease mechanisms to a new classification. Human Genetics, 141:709-735, Mar 2022. URL: https://doi.org/10.1007/s00439-022-02448-7, doi:10.1007/s00439-022-02448-7. This article has 170 citations and is from a peer-reviewed journal.
(zou2014deletionofpdzd7 pages 6-7): Junhuang Zou, Tihua Zheng, Chongyu Ren, Charles Askew, Xiao-Ping Liu, Bifeng Pan, Jeffrey R. Holt, Yong Wang, and Jun Yang. Deletion of pdzd7 disrupts the usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice. Human molecular genetics, 23 9:2374-90, May 2014. URL: https://doi.org/10.1093/hmg/ddt629, doi:10.1093/hmg/ddt629. This article has 78 citations and is from a domain leading peer-reviewed journal.
(zou2014deletionofpdzd7 pages 12-12): Junhuang Zou, Tihua Zheng, Chongyu Ren, Charles Askew, Xiao-Ping Liu, Bifeng Pan, Jeffrey R. Holt, Yong Wang, and Jun Yang. Deletion of pdzd7 disrupts the usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice. Human molecular genetics, 23 9:2374-90, May 2014. URL: https://doi.org/10.1093/hmg/ddt629, doi:10.1093/hmg/ddt629. This article has 78 citations and is from a domain leading peer-reviewed journal.
(zou2014deletionofpdzd7 pages 10-12): Junhuang Zou, Tihua Zheng, Chongyu Ren, Charles Askew, Xiao-Ping Liu, Bifeng Pan, Jeffrey R. Holt, Yong Wang, and Jun Yang. Deletion of pdzd7 disrupts the usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice. Human molecular genetics, 23 9:2374-90, May 2014. URL: https://doi.org/10.1093/hmg/ddt629, doi:10.1093/hmg/ddt629. This article has 78 citations and is from a domain leading peer-reviewed journal.
(zou2017therolesof pages 8-9): Junhuang Zou, Qian Chen, Ali Almishaal, Pranav Dinesh Mathur, Tihua Zheng, Cong Tian, Qing Y. Zheng, and Jun Yang. The roles of ush1 proteins and pdz domain‐containing ush proteins in ush2 complex integrity in cochlear hair cells. Human Molecular Genetics, 26:624–636, Dec 2017. URL: https://doi.org/10.1093/hmg/ddw421, doi:10.1093/hmg/ddw421. This article has 51 citations and is from a domain leading peer-reviewed journal.
(wang2023temporalandspatial pages 2-3): Huang Wang, Haibo Du, Rui Ren, Tingting Du, Lin Lin, Zhe Feng, Dange Zhao, Xiaoxi Wei, Xiaoyan Zhai, Hongyang Wang, Tingting Dong, Jin-Peng Sun, Hao Wu, Zhigang Xu, and Qing Lu. Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation. Nature Communications, Mar 2023. URL: https://doi.org/10.1038/s41467-023-37267-5, doi:10.1038/s41467-023-37267-5. This article has 17 citations and is from a highest quality peer-reviewed journal.
(zou2017therolesof pages 1-1): Junhuang Zou, Qian Chen, Ali Almishaal, Pranav Dinesh Mathur, Tihua Zheng, Cong Tian, Qing Y. Zheng, and Jun Yang. The roles of ush1 proteins and pdz domain‐containing ush proteins in ush2 complex integrity in cochlear hair cells. Human Molecular Genetics, 26:624–636, Dec 2017. URL: https://doi.org/10.1093/hmg/ddw421, doi:10.1093/hmg/ddw421. This article has 51 citations and is from a domain leading peer-reviewed journal.
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(nouri2024clinicalcharacterizationsand pages 5-6): Zahra Nouri, Akram Sarmadi, Sina Narrei, Hamidreza Kianersi, Farzan Kianersi, and Mohammad Amin Tabatabaiefar. Clinical characterizations and molecular genetic study of two co-segregating variants in pdzd7 and pde6c genes leading simultaneously to non-syndromic hearing loss and achromatopsia. BMC Medical Genomics, Jul 2024. URL: https://doi.org/10.1186/s12920-024-01942-3, doi:10.1186/s12920-024-01942-3. This article has 4 citations and is from a peer-reviewed journal.