TABLE 1.
Growth factors, receptors and related proteins implicated in nonsyndromic hearing loss
| Gene | OMIM | Description; cellular location | Protein/alias | Function | HL type | Locus† |
|---|---|---|---|---|---|---|
| ADCY1 | 103072 | Adenylate Cyclase 1; transmembrane | ADCY1/AC1 | Generates the second messenger cAMP | Prelingual, sensorineural, bilateral, profound | DFNB44 |
| CCDC50 | 611051 | Coiled Coil Domain-Containing protein 50; cytoplasmic | CCDC50/YMER/C3ORF6 | Inhibits downregulation of EGFR/Effector of EGF mediated signaling | Postlingual, progressive, sensorineural, mid-frequency> | DFNA44 |
| DCDC2 | 605755 | Double Cortin Domain-Containing protein 2; cytoplasmic | DCDC2/RU2/RU2S | Inhibits WNT signaling | Prelingual, sensorineural, profound | DFNB66 |
| ELMOD3 | 615427 | ELMO/ced12 Domain-containing protein 3; cytoplasmic | ELMOD3/RBED1 | GTPase-activating protein (GAP) for small GTPases | Prelingual, mixed, severe to profound | DFNB88 |
| EPS8 | 600206 | Epidermal growth factor receptor Pathway Substrate 8; cytoplasmic | EPS8 | Elongation of stereocilia by actin remodeling | Prelingual, sensorineural, bilateral, profound | DFNB102 |
| EPS8L2 | 614988 | Epidermal growth factor receptor Pathway Substrate 8-Like protein 2; cytoplasmic |
EPS8L2 | Maintenance of stereocilia, actin remodeling | Childhood onset, progressive, bilateral, sensorineural, moderate to profound | DFNB106 |
| ESRRB | 602167 | EStrogen-Related Receptor, Beta; cytoplasmic | ESRRB/ESRL2/ERR2 | Epithelial cell fate, development of the stria vascularis | Prelingual or postlingual, sensorineural, bilateral, severe to profound | DFNB35 |
| GAB1 | 604439 | GRB2-Associated Binding protein 1; cytoplasmic | GAB1 | Mediator of HGF, IGF1 signaling | Prelingual, bilateral, sensorineural, profound | DFNB26 |
| GIPC3 | 608792 | GIPC PDZ domain-containing family, member 3; cytoplasmic | GIPC3/GAIP C-terminus-interacting protein 3 | Predicted to modulate WNT signaling | Prelingual, bilateral, sensorineural, severe to profound | DFNB15/DFNB72/DFNB95 |
| GRAP | 604330 | Growth factor Receptor-bound protein 2 (Grb2)-related Adaptor Protein; cytoplasmic | GRAP | Activates RAS signaling | Prelingual, bilateral, sensorineural, severe to profound | DFNB114 |
| HGF | 142409 | Hepatocyte Growth Factor; secreted | HGF/SF | Incorporation of neural crest cells into the stria vascularis | Prelingual, sensorineural, bilateral, moderate to severe or severe to profound | DFNB39 |
| IFNLR1 | 607404 | Interferon-Lambda Receptor 1, transmembrane | IFNLR1/ IL28RA | Functions in Jak/STAT pathway | Postlingual, sensorineural, bilateral, progressive, moderate to profound | DFNA2C |
| ILDR1 | 609739 | Immunoglobulin-Like Domain-containing Receptor 1; transmembrane and cytoplasmic | ILDR1 | Structural role at the tricellular tight junctions; receptor role in the inner ear unknown | Prelingual, sensorineural, bilateral, moderate to profound or severe to profound | DFNB42 |
| KITLG | 184745 | KIT Ligand; transmembrane and secreted | KITLG/KL/KITL/MGF/SCF/SF | Proliferation, migration from the neural crest, differentiation of melanoblasts | Prelingual, sensorineural, unilateral or asymmetric | DFNA69 |
| LRP5 | 603506 | Low density lipoprotein Receptor-related Protein 5; transmembrane | LRP5/LRP7/LR3 | Co-receptor during WNT signaling | Sensorineural, progressive, childhood onset, bilateral, low and mid frequency | -, recessive |
| MET | 164860 | Mesenchymal EpithelialTransition factor; transmembrane | MET/HGFR | Incorporation of neural crest cells into the stria vascularis | Prelingual, sensorineural, bilateral, severe | DFNB97 |
| NLRP3 | 606416 | NLR family, Pyrin domain-containing 3; cytoplasmic | NLRP3/CIAS1/NALP3/PYPAF1/ AII/AVP Receptor-Like | Leads to events which end in production of cytokine IL-1β | Postlingual, bilateral, progressive | DFNA34 |
| PDE1C | 602987 | Phosphodiesterase 1C; cytoplasmic | PDE1C/HCAM3 | Regulates levels of second messengers cAMP and cGMP | Postlingual, progressive, bilateral, mild to profound | DFNA74 |
| PTPRQ | 603317 | Protein-Tyrosine Phosphatase, Receptor-type, Q; transmembrane and cytoplasmic | PTPRQ/ PTPGMC1 | Receptor role unknown, structural role as shaft connector | Sensorineural, variable onset, progressive, bilateral, mild to moderate | DFNA73 |
| PTPRQ | 603317 | Protein-Tyrosine Phosphatase, Receptor-type, Q; transmembrane and cytoplasmic | PTPRQ/ PTPGMC1 | Receptor role unknown, structural role as shaft connector | Sensorineural, childhood onset, progressive, bilateral, moderate to profound | DFNB84A |
| ROR1 | 602336 | Receptor tyrosine kinase-like Orphan Receptor 1; transmembrane | ROR1/ NTRKR1 | Innervation of auditory hair cells in response to WNT5A signaling | Prelingual, bilateral, sensironeural, profound, auditory neuropathy, | DFNB108 |
| S1PR2 | 605111 | Sphingosine-1-Phosphate Receptor 2; transmembrane & cytoplasmic | S1PR2/EDG5/S1P2 | Development of stria vascularis | Congenital, sensorineural, bilateral, profound | DFNB68 |
†
DFNA, dominant hearing loss, DFNB, recessive hearing loss, OMIM, Online Mendelian Inheritance in Man (https://www.omim.org/). A comprehensive source of gene expression data in mouse and zebrafish auditory systems are available on the gEAR Portal, https://umgear.org/.