DIAPH1

Summary

DIAPH1 (diaphanous related formin 1, HGNC:2876) is a protein-coding gene on chromosome 5q31.3, encoding Protein diaphanous homolog 1 (O60610). Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers.

This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 1729 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive microcephaly-seizures-cortical blindness-developmental delay syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 1,897 total — 36 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• MANE Select transcript: NM_005219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2876
Approved symbol	DIAPH1
Name	diaphanous related formin 1
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	hDIA1, LFHL1, mDia1
Ensembl gene	ENSG00000131504
Ensembl biotype	protein_coding
OMIM	602121
Entrez	1729

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000389054, ENST00000448451, ENST00000468119, ENST00000472516, ENST00000476339, ENST00000491754, ENST00000494967, ENST00000518047, ENST00000518484, ENST00000523100, ENST00000524301, ENST00000643312, ENST00000643718, ENST00000647330, ENST00000647433

RefSeq mRNA: 3 — MANE Select: NM_005219 NM_001079812, NM_001314007, NM_005219

CCDS: CCDS43373, CCDS43374, CCDS87331

Canonical transcript exons

ENST00000389054 — 28 exons

Exon	Start	End
ENSE00001504786	141571926	141572040
ENSE00002433803	141583485	141583615
ENSE00002447549	141583206	141583292
ENSE00002453535	141577475	141577591
ENSE00002467863	141584124	141584225
ENSE00002468421	141582312	141582375
ENSE00002474822	141574967	141575146
ENSE00002484253	141576756	141576871
ENSE00002486835	141573492	141574208
ENSE00002505979	141580744	141580883
ENSE00002524976	141576230	141576294
ENSE00003460486	141578515	141578625
ENSE00003463207	141578225	141578343
ENSE00003478221	141579088	141579196
ENSE00003489171	141528453	141528582
ENSE00003491307	141528702	141528941
ENSE00003517610	141515021	141517008
ENSE00003541262	141526038	141526173
ENSE00003548898	141587042	141587197
ENSE00003584222	141527573	141527697
ENSE00003593301	141534335	141534433
ENSE00003598560	141524143	141524229
ENSE00003605990	141529603	141529697
ENSE00003677015	141526297	141526461
ENSE00003690253	141529172	141529273
ENSE00003723728	141588224	141588250
ENSE00003769475	141571428	141571436
ENSE00003847922	141618798	141619000

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.4788 / max 1070.9863, expressed in 1817 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63852	29.6259	1812
63853	3.7285	1455
63850	1.9398	1126
63854	1.1095	700
63851	0.6310	405
63845	0.2055	76
63855	0.1643	57
63843	0.0744	33

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.43	gold quality
lower esophagus mucosa	UBERON:0035834	97.96	gold quality
leukocyte	CL:0000738	97.38	gold quality
monocyte	CL:0000576	97.31	gold quality
mononuclear cell	CL:0000842	97.27	gold quality
calcaneal tendon	UBERON:0003701	97.14	gold quality
right lobe of liver	UBERON:0001114	97.12	gold quality
gastrocnemius	UBERON:0001388	97.09	gold quality
muscle of leg	UBERON:0001383	96.60	gold quality
esophagus mucosa	UBERON:0002469	96.25	gold quality
skin of leg	UBERON:0001511	96.05	gold quality
right lung	UBERON:0002167	96.03	gold quality
upper lobe of left lung	UBERON:0008952	95.96	gold quality
blood	UBERON:0000178	95.90	gold quality
amniotic fluid	UBERON:0000173	95.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.40	gold quality
upper lobe of lung	UBERON:0008948	95.38	gold quality
islet of Langerhans	UBERON:0000006	95.32	gold quality
body of pancreas	UBERON:0001150	95.32	gold quality
skin of abdomen	UBERON:0001416	95.31	gold quality
tendon	UBERON:0000043	95.07	gold quality
liver	UBERON:0002107	94.97	gold quality
tonsil	UBERON:0002372	94.96	gold quality
lymph node	UBERON:0000029	94.94	gold quality
pancreas	UBERON:0001264	94.93	gold quality
metanephros cortex	UBERON:0010533	94.79	gold quality
gingival epithelium	UBERON:0001949	94.76	gold quality
apex of heart	UBERON:0002098	94.66	gold quality
colonic epithelium	UBERON:0000397	94.65	gold quality
bone marrow cell	CL:0002092	94.64	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF, TBXT

miRNA regulators (miRDB)

100 targeting DIAPH1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 40)

• ROCK and Dia have opposing effects on adherens junctions downstream of Rho. (PMID:11992112)
• mDia influences Pax6-induced transcriptional activity and axonal pathfinding in a way opposite from ROCK (Rho kinase) and that it may act via Pax6 to modulate early neuronal development (PMID:12324464)
• pertains to studies in mouse (PMID:12324464)
• mDia is present in very small amounts in freshly isolated peripheral blood lymphocytes, is induced in vivo and in vitro during T cell activation, and is involved in regulating the F-actin/G-actin balance critical for T cell motility. (PMID:12847276)
• RhoA, mDia, and ROCK have roles in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition (PMID:15096506)
• Results show that mDia1 and PKD2 interact in native and in transfected cells, and binding is mediated by the cytoplasmic C terminus of PKD2 binding to the mDia1 N terminus. (PMID:15123714)
• findings show that in melanomas invasiveness can be regulated epigenetically by the microphthalmia-associated transcription factor, Mitf, by regulation of the DIAPH1 gene; Mitf, via regulation of Dia1, can both inhibit invasiveness & promote proliferation (PMID:17182868)
• Increases in GTP-bound RHOA and DIAPH1 expression may contribute to the increase in uterine activity in idiopathic preterm labor. (PMID:17301291)
• Data suggest that Dia1 localizes to and controls E-cadherin-mediated junctions in a RhoA-dependent manner. (PMID:17940061)
• Angiopoietin 1 promotes the activation of mDia through RhoA, resulting in the association of mDia with Src. [mD1a] (PMID:18194650)
• mDia1 and Daam1 are platelet actin assembly factors having distinct efficiencies, and they are directly regulated by Rho GTPases (PMID:18218625)
• the interaction of the RAGE cytoplasmic domain with Dia-1 is required to transduce extracellular environmental cues evoked by binding of RAGE ligands to their cell surface receptor, resulting in Rac-1 and Cdc42 activation and cellular migration (PMID:18922799)
• Memo-RhoA-mDia1 signaling coordinates the organization of the lamellipodial actin network, adhesion site formation, and microtubule outgrowth within the cell leading edge to sustain cell motility. (PMID:18955552)
• Flies with mutations affecting the diaphanous,forked, and CG12026/TMHS genes displayed significant reductions in the amplitude of sound-evoked potentials compared to wild-type flies (PMID:19102128)
• These findings uncover a novel link between cadherin-mediated adhesion and the regulation of actin dynamics through the requirement for an Abi/Dia complex for the formation and stability of cell-cell junctions. (PMID:19158278)
• Rho mediates various phenotypes of malignant transformation by Ras and Src through its effectors, ROCK and mDia [review] (PMID:19160018)
• mDia1 was shown to translocate to the platelet cytoskeleton following thrombin stimulation, in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner. (PMID:19470376)
• loss of hDia1 did not disrupt actin assembly at the lytic synapse. Instead, loss of hDia1 led to perturbations in the microtubule cytoskeleton, including the targeting of microtubules to the lytic synapse (PMID:19913427)
• PI3-kinase regulates the thrombin-induced actin cytoskeleton reconstitution in platelets by the RhoA-mDia1 pathway. (PMID:20030946)
• mDia plays an important role in the development of force-induced transcriptional activation of SMA and myofibroblast differentiation (PMID:20071339)
• Fli-I promotes the GTP-bound active Rho-mediated relief of the autoinhibition of Daam1 and mDia1. Thus, Fli-I is a novel positive regulator of Rho-induced linear actin assembly mediated by DRFs. (PMID:20223827)
• Data show that expression of a dominant-negative RhoA mutant or silencing DIAPH1 impaired mitochondrial trafficking and cortisol biosynthesis. (PMID:20591975)
• mDia1 regulates Golgi architecture and dynamics in a Rho-dependent manner (PMID:21680709)
• mDia1 and WAVE2 are important Src homology 3 domain partners of IRSp53 in forming filopodia. (PMID:22179776)
• a novel mechanism through which an extracellular signal initiated by RAGE ligands regulates RAGE signaling in a manner requiring mDia1. (PMID:22194616)
• Liprin-alpha negatively regulates the activity of mDia in the cell by displacing it from the plasma membrane through binding to the N-terminal Dia-inhibitory domain (DID) and dimerization domain (DD) of mDia (PMID:22266902)
• mDia1 knockdown results in Cav1/caveolae clustering and defective inward trafficking upon loss of cell adhesion. (PMID:22454521)
• findings show that DIAPH1 interacts with multiple proteins in H295R human adrenocortical cells and that cAMP signaling modulates the interaction of a subset of proteins with DIAPH1 (PMID:23325789)
• Depletion of DIAPH1 reduced metastasis 60-fold. (PMID:24105619)
• Recruitment of Syx to the cell membrane, the selective activation of Dia1 signaling, coupled with the suppression of ROCK and actin reorganization, plays a key role in establishing cell polarity during directed cell migration. (PMID:24126053)
• The results revealed that treatment with siRNA-mDRF1 significantly inhibited tumor growth and led to a decrease in the weight of the transplanted tumor. In conclusion, our data demonstrate that mDRF1 is highly expressed in human glioma tissue. (PMID:24317603)
• Dia1, Dia2, and Dia3 are involved in ErbB2-dependent capture of microtubules at the cell leading edge and ErbB2-driven guided migration. (PMID:24403606)
• Patients with a homozygous nonsense DIAPH1 alteration (p.Gln778*) have MCP as well as reduced height and weight. (PMID:24781755)
• Mechanistically, mDia1 deficiency led to a downregulation of membrane-associated genes and a specific upregulation of CD14 messenger RNA in granulocytes, but not in other lineages. (PMID:24891322)
• the RhoA-regulated formin Dia1 is involved in entosis downstream of LPAR2 (PMID:24950964)
• DIAPH1 has a critical role in generating F-actin structures and assisting the microtubule stabilization underlying proplatelet formation and platelet production (PMID:25298036)
• Data indicate that diaphanous homolog 1 (Drosophila) protein (DIAPH1) stabilizes microtubules and reduces microtubule dynamics. (PMID:26124177)
• The Rho-mDia1 signaling pathway is involved in the cytoskeletal rearrangement of human periodontal ligament cells induced by cyclic strain. (PMID:26201082)
• functional complementation experiments and optogenetics to show that mDia1 cooperates with the Arp2/3 complex in initiating lamellipodia and ruffles. (PMID:26349808)
• Loss-of-function variants in DIAPH1 is associated with syndromic microcephaly, blindness, and early onset seizures. (PMID:26463574)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000115082
mus_musculus	Diaph1	ENSMUSG00000024456
rattus_norvegicus	Diaph1	ENSRNOG00000019688
drosophila_melanogaster	Frl	FBGN0267795
caenorhabditis_elegans	fhod-1	WBGENE00016735
caenorhabditis_elegans		WBGENE00018976
caenorhabditis_elegans		WBGENE00019030
caenorhabditis_elegans	sydn-1	WBGENE00021473
caenorhabditis_elegans		WBGENE00021698

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), FHDC1 (ENSG00000137460), DIAPH3 (ENSG00000139734), DAAM2 (ENSG00000146122), DIAPH2 (ENSG00000147202), FMN2 (ENSG00000155816), FMNL2 (ENSG00000157827), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485), GRID2IP (ENSG00000215045)

Protein

Protein identifiers

Protein diaphanous homolog 1 — O60610 (reviewed: O60610)

Alternative names: Diaphanous-related formin-1

All UniProt accessions (5): A0A2R8Y5N1, A0A2R8YEF8, B4E2I7, H7C2W8, O60610

UniProt curated annotations — full annotation on UniProt →

Function. Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers. Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization. Required for cytokinesis, and transcriptional activation of the serum response factor. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration. Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane. In hear cells, it may play a role in the regulation of actin polymerization in hair cells. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. Plays a role in brain development. Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity.

Subunit / interactions. Homodimer. Interacts with the GTP-bound form of RHOA. Interacts with RHOC, PFY1, MAPRE1 and BAIAP2. Interacts with APC; acts as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration. Interacts with SCAI. Interacts with DCAF7, via FH2 domain. Interacts with NCDN. Interacts with OSBPL10, OSBPL2, VIM, TUBB and DYN1.

Subcellular location. Cell membrane. Cell projection. Ruffle membrane. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Nucleus.

Tissue specificity. Expressed in brain, heart, placenta, lung, kidney, pancreas, liver, skeletal muscle and cochlea. Expressed in platelets.

Post-translational modifications. Phosphorylation at Thr-768 is stimulated by cAMP and regulates stability, complex formation and mitochondrial movement.

Disease relevance. Deafness, autosomal dominant 1, with or without thrombocytopenia (DFNA1) [MIM:124900] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Patients may have mild thrombocytopenia and enlarged platelets, although most of DFNA1 affected individuals do not have significant bleeding tendencies. The disease is caused by variants affecting the gene represented in this entry. Seizures, cortical blindness, and microcephaly syndrome (SCBMS) [MIM:616632] A severe autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, short stature, and cortical blindness. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.

Similarity. Belongs to the formin homology family. Diaphanous subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O60610-1	1	yes
O60610-2	2
O60610-3	3

RefSeq proteins (3): NP_001073280, NP_001300936, NP_005210* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010465	Drf_DAD	Domain
IPR010472	FH3_dom	Domain
IPR010473	GTPase-bd	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR014767	DAD_dom	Domain
IPR014768	GBD/FH3_dom	Domain
IPR015425	FH2_Formin	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR044933	DIA_GBD_sf	Homologous_superfamily
IPR051412	Formin_Homology_Diaphanous_sf	Family

Pfam: PF02181, PF06345, PF06346, PF06367, PF06371

UniProt features (58 total): helix 16, modified residue 10, compositionally biased region 8, domain 4, mutagenesis site 4, sequence conflict 4, splice variant 3, sequence variant 2, turn 2, region of interest 2, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8FG1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60610-F1	74.04	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 1, 7, 22, 36, 768, 1057, 1103, 1121, 1251, 1254

Mutagenesis-validated functional residues (4):

Position	Phenotype
154	partial decrease of phosphorylation.
768	substantial loss of phosphorylation, no increase of phosphorylation in response to camp, increased stability, reduced in
1091	substantial loss of phosphorylation.
1238	substantial loss of phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6785631	ERBB2 Regulates Cell Motility
R-HSA-6798695	Neutrophil degranulation
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-9854909	Regulation of MITF-M dependent genes involved in invasion

MSigDB gene sets: 461 (showing top): BIOCARTA_RHO_PATHWAY, RNGTGGGC_UNKNOWN, AGGAAGC_MIR5163P, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, BIOCARTA_MAL_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_SECRETORY_GRANULE, MORF_SNRP70, MORF_HDAC1, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, AREB6_01

GO Biological Process (11): cytoskeleton organization (GO:0007010), sensory perception of sound (GO:0007605), regulation of cell shape (GO:0008360), actin cytoskeleton organization (GO:0030036), actin filament polymerization (GO:0030041), regulation of microtubule-based process (GO:0032886), protein localization to microtubule (GO:0035372), regulation of release of sequestered calcium ion into cytosol (GO:0051279), regulation of cytoskeleton organization (GO:0051493), cellular response to histamine (GO:0071420), cellular component organization (GO:0016043)

GO Molecular Function (6): RNA binding (GO:0003723), actin binding (GO:0003779), signaling receptor binding (GO:0005102), small GTPase binding (GO:0031267), transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), secretory granule membrane (GO:0030667), ruffle membrane (GO:0032587), mitotic spindle (GO:0072686), ficolin-1-rich granule membrane (GO:0101003), spindle (GO:0005819), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	5
RHO GTPase Effectors	1
Signaling by ERBB2	1
Innate Immune System	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoskeleton organization	2
protein binding	2
intracellular membraneless organelle	2
organelle organization	1
sensory perception of mechanical stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
actin filament-based process	1
actin polymerization or depolymerization	1
protein polymerization	1
microtubule-based process	1
regulation of cellular process	1
protein localization to microtubule cytoskeleton	1
release of sequestered calcium ion into cytosol	1
regulation of calcium ion transmembrane transport	1
regulation of organelle organization	1
response to histamine	1
cellular response to nitrogen compound	1
cellular component organization or biogenesis	1
nucleic acid binding	1
cytoskeletal protein binding	1
GTPase binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
spindle	1

Protein interactions and networks

STRING

2037 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIAPH1	SAV1	Q9H4B6	862
DIAPH1	RHOC	P08134	845
DIAPH1	RHOA	P06749	828
DIAPH1	EIF3M	Q7L2H7	767
DIAPH1	GFER	P55789	747
DIAPH1	WFS1	O76024	730
DIAPH1	PFN4	Q8NHR9	714
DIAPH1	RHOD	O00212	705
DIAPH1	POU4F3	Q15319	674
DIAPH1	PCSK9	Q8NBP7	668
DIAPH1	PFN1	P07737	656
DIAPH1	PFN3	P60673	654
DIAPH1	LIMK1	P53667	652
DIAPH1	AGER	Q15109	641
DIAPH1	WAS	P42768	628

IntAct

84 interactions, top by confidence:

A	B	Type	Score
DCAF7	DIAPH1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RHOD	PLXNB2	psi-mi:“MI:0914”(association)	0.640
RHOA	DIAPH1	psi-mi:“MI:0914”(association)	0.600
RHOA	DIAPH1	psi-mi:“MI:0407”(direct interaction)	0.600
DIAPH1	RHOA	psi-mi:“MI:0407”(direct interaction)	0.600
RHOC	DIAPH1	psi-mi:“MI:0407”(direct interaction)	0.590
RHOD	DIAPH1	psi-mi:“MI:0407”(direct interaction)	0.590
AGER	DIAPH1	psi-mi:“MI:0915”(physical association)	0.580
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
ORF	EIF3D	psi-mi:“MI:0914”(association)	0.560
DIAPH1	PPM1F	psi-mi:“MI:0915”(physical association)	0.540
DIAPH1	PPM1F	psi-mi:“MI:0407”(direct interaction)	0.540
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
RHOC	ARHGEF11	psi-mi:“MI:0914”(association)	0.530
DIAPH1	PKD2	psi-mi:“MI:0403”(colocalization)	0.530
PKD2	DIAPH1	psi-mi:“MI:0915”(physical association)	0.530
ORF	DIAPH1	psi-mi:“MI:0915”(physical association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
DIAPH1	DIAPH1	psi-mi:“MI:0407”(direct interaction)	0.440
DIAPH1	RHOB	psi-mi:“MI:0407”(direct interaction)	0.440
DIAPH1	RHOF	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (195): DIAPH1 (Affinity Capture-MS), DIAPH1 (Affinity Capture-MS), DIAPH1 (Affinity Capture-MS), DIAPH1 (Co-fractionation), DIAPH1 (Co-fractionation), MTOR (Co-fractionation), TLN2 (Co-fractionation), TTC4 (Co-fractionation), UBL7 (Co-fractionation), DIAPH1 (Affinity Capture-MS), DIAPH1 (Affinity Capture-MS), LRP1 (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), SLC16A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5P556, A0A3Q1LSX9, A2A5R2, A2APV2, B0DOB5, B2RQE8, D3ZYR1, D4A631, F1LVW7, F1M775, F4IUX6, G3X9K3, O08808, O46382, O60308, O60610, O75674, O95466, Q07139, Q0IHV1, Q0JRZ9, Q3UQN2, Q4S6U8, Q5MIZ7, Q5R807, Q5SP90, Q6DFT3, Q6IN85, Q6INN7, Q6NTV6, Q6NXC0, Q6P2K6, Q6ZPF4, Q7TSU1, Q7ZX60, Q801Q7, Q80U19, Q86T65, Q8BPM0, Q8IVF7

Diamond homologs: A0A1D5P556, A4D2P6, B0DOB5, O08808, O23373, O60610, O70566, Q6MWG9, Q80U19, Q86T65, Q8BPM0, Q9FJX6, Q9Y4D1, A3AB67, F1LVW7, F1M775, O60879, P48608, Q0D519, Q0D5P3, Q10Q99, Q6H7U3, Q8H8K7, Q8S0F0, Q9MA60, Q9NSV4, Q9Z207, O04532, Q10059, Q27J81, Q54N00, Q54WH2, Q69MT2, Q9XIE0, A2XUA1, A2YVG8, O22824, O48682, P0C5K5, Q0DLG0

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
RHOA	“up-regulates activity”	DIAPH1
DIAPH1	“up-regulates activity”	CDH4
ERK1/2	“up-regulates quantity by stabilization”	DIAPH1	phosphorylation
PKA	“up-regulates quantity by stabilization”	DIAPH1	phosphorylation
CHEK1	“down-regulates activity”	DIAPH1	phosphorylation
CDK1	“down-regulates activity”	DIAPH1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases Activate Formins	7	9.7×	1e-03
mRNA Splicing - Major Pathway	7	6.8×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
Rho protein signal transduction	6	23.2×	8e-05
regulation of actin cytoskeleton organization	7	17.2×	8e-05
mRNA splicing, via spliceosome	7	10.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1897 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	36
Likely pathogenic	25
Uncertain significance	974
Likely benign	704
Benign	46

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027661	NM_005219.5(DIAPH1):c.3490C>T (p.Arg1164Ter)	Pathogenic
1070912	NM_005219.5(DIAPH1):c.108dup (p.Lys37Ter)	Pathogenic
1076722	NM_005219.5(DIAPH1):c.3022C>T (p.Arg1008Ter)	Pathogenic
1356050	NM_005219.5(DIAPH1):c.3166C>T (p.Gln1056Ter)	Pathogenic
1360681	NM_005219.5(DIAPH1):c.2100dup (p.Pro701fs)	Pathogenic
1395984	NM_005219.5(DIAPH1):c.2108dup (p.Pro704fs)	Pathogenic
1402630	NM_005219.5(DIAPH1):c.1016del (p.Met339fs)	Pathogenic
1413320	NM_005219.5(DIAPH1):c.910dup (p.Ser304fs)	Pathogenic
1923492	NM_005219.5(DIAPH1):c.626dup (p.Tyr209Ter)	Pathogenic
1949957	NM_005219.5(DIAPH1):c.1483C>T (p.Arg495Ter)	Pathogenic
1990251	NM_005219.5(DIAPH1):c.1051C>T (p.Arg351Ter)	Pathogenic
2095210	NM_005219.5(DIAPH1):c.2350_2351dup (p.Trp784fs)	Pathogenic
2097632	NM_005219.5(DIAPH1):c.3211_3212insAT (p.Arg1071fs)	Pathogenic
217753	NM_005219.5(DIAPH1):c.2769del (p.Phe923fs)	Pathogenic
217754	NM_005219.5(DIAPH1):c.3145C>T (p.Arg1049Ter)	Pathogenic
228577	NM_005219.5(DIAPH1):c.3637C>T (p.Arg1213Ter)	Pathogenic
2935331	NM_005219.5(DIAPH1):c.684+1G>A	Pathogenic
2953190	NM_005219.5(DIAPH1):c.89del (p.Gly30fs)	Pathogenic
2953941	NM_005219.5(DIAPH1):c.839del (p.Leu280fs)	Pathogenic
3246410	NC_000005.9:g.(?140998345)(140998481_?)del	Pathogenic
3748740	NM_005219.5(DIAPH1):c.991C>T (p.Arg331Ter)	Pathogenic
3750274	NM_005219.5(DIAPH1):c.811C>T (p.Gln271Ter)	Pathogenic
3752601	NM_005219.5(DIAPH1):c.30del (p.Gly11fs)	Pathogenic
3754264	NM_005219.5(DIAPH1):c.2108del (p.Pro703fs)	Pathogenic
3756314	NM_005219.5(DIAPH1):c.1609del (p.Leu537fs)	Pathogenic
3760376	NM_005219.5(DIAPH1):c.3516del (p.Glu1173fs)	Pathogenic
391928	NM_005219.5(DIAPH1):c.2794C>T (p.Arg932Ter)	Pathogenic
419689	NM_005219.5(DIAPH1):c.1971_1972delinsT (p.Leu657fs)	Pathogenic
424874	NM_005219.5(DIAPH1):c.3624_3625del (p.Ala1210fs)	Pathogenic
504168	NM_005219.5(DIAPH1):c.2905_2906dup (p.Ser970fs)	Pathogenic

SpliceAI

4202 predictions. Top by Δscore:

Variant	Effect	Δscore
5:141524138:CTTA:C	donor_gain	1.0000
5:141524139:TTAC:T	donor_loss	1.0000
5:141524140:TA:T	donor_loss	1.0000
5:141524141:A:AC	donor_gain	1.0000
5:141524141:A:AG	donor_loss	1.0000
5:141524141:AC:A	donor_gain	1.0000
5:141524142:C:CC	donor_gain	1.0000
5:141524142:CC:C	donor_gain	1.0000
5:141524225:GCCCT:G	acceptor_gain	1.0000
5:141524226:CCCT:C	acceptor_gain	1.0000
5:141524226:CCCTC:C	acceptor_gain	1.0000
5:141524227:CCT:C	acceptor_gain	1.0000
5:141524227:CCTC:C	acceptor_gain	1.0000
5:141524228:CT:C	acceptor_gain	1.0000
5:141524228:CTC:C	acceptor_gain	1.0000
5:141524228:CTCTG:C	acceptor_loss	1.0000
5:141524229:TCT:T	acceptor_gain	1.0000
5:141524229:TCTGT:T	acceptor_loss	1.0000
5:141524230:C:CC	acceptor_gain	1.0000
5:141524230:CT:C	acceptor_loss	1.0000
5:141524231:T:A	acceptor_loss	1.0000
5:141524233:T:C	acceptor_gain	1.0000
5:141524233:T:TC	acceptor_gain	1.0000
5:141526032:CCTCA:C	donor_loss	1.0000
5:141526033:CTCAC:C	donor_loss	1.0000
5:141526034:TCAC:T	donor_loss	1.0000
5:141526035:CACCT:C	donor_loss	1.0000
5:141526037:C:CA	donor_loss	1.0000
5:141526037:CCTG:C	donor_gain	1.0000
5:141526170:CTTG:C	acceptor_gain	1.0000

AlphaMissense

8377 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:141524168:G:C	F1212L	1.000
5:141524168:G:T	F1212L	1.000
5:141524170:A:G	F1212L	1.000
5:141524178:C:T	G1209E	1.000
5:141524179:C:A	G1209W	1.000
5:141524187:A:G	L1206P	1.000
5:141524191:C:G	A1205P	1.000
5:141524199:A:G	L1202P	1.000
5:141524206:C:G	D1200H	1.000
5:141528727:C:T	G998D	1.000
5:141528910:A:G	L937P	1.000
5:141529269:A:G	L894P	1.000
5:141529694:A:G	I862T	1.000
5:141529694:A:T	I862N	1.000
5:141534337:A:G	L860P	1.000
5:141573500:A:G	W784R	1.000
5:141573500:A:T	W784R	1.000
5:141578546:A:G	L338P	1.000
5:141578609:A:G	L317P	1.000
5:141580879:C:T	G230E	1.000
5:141582318:G:C	N226K	1.000
5:141582318:G:T	N226K	1.000
5:141582338:A:G	C220R	1.000
5:141583289:C:A	W179C	1.000
5:141583289:C:G	W179C	1.000
5:141583291:A:G	W179R	1.000
5:141583291:A:T	W179R	1.000
5:141583503:A:G	L172P	1.000
5:141583503:A:T	L172H	1.000
5:141583515:A:G	L168P	1.000

dbSNP variants (sampled 300 via entrez): RS1000034300 (5:141569068 A>G), RS1000051509 (5:141524869 A>C,T), RS1000120819 (5:141570597 C>T), RS1000132010 (5:141584623 T>C), RS1000220468 (5:141572325 G>A,C,T), RS1000242019 (5:141606871 G>C), RS1000267776 (5:141523484 T>G), RS1000273476 (5:141575671 A>C), RS1000290688 (5:141619000 A>C,G,T), RS1000366902 (5:141538111 A>G), RS1000367028 (5:141553828 G>A), RS1000374807 (5:141538516 T>G), RS1000407078 (5:141569384 A>C), RS1000427143 (5:141538356 G>A), RS1000434329 (5:141560300 A>C)

Disease associations

OMIM: gene MIM:602121 | disease phenotypes: MIM:124900, MIM:616632, MIM:274600, MIM:248510

GenCC curated gene-disease

Disease	Classification	Inheritance
DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome	Definitive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 1	Strong	Autosomal dominant
progressive microcephaly-seizures-cortical blindness-developmental delay syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
progressive microcephaly-seizures-cortical blindness-developmental delay syndrome	Definitive	AR
DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome	Definitive	AD

Mondo (10): autosomal dominant nonsyndromic hearing loss 1 (MONDO:0007424), progressive microcephaly-seizures-cortical blindness-developmental delay syndrome (MONDO:0014714), hearing loss disorder (MONDO:0005365), Pendred syndrome (MONDO:0010134), vascular dementia (MONDO:0004648), microcephaly (MONDO:0001149), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071), beta-mannosidosis (MONDO:0009562), DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome (MONDO:0044635)

Orphanet (7): Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome (Orphanet:477814), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Pendred syndrome (Orphanet:705), Rare genetic deafness (Orphanet:96210), Beta-mannosidosis (Orphanet:118), DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome (Orphanet:494444), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000648	Optic atrophy
HP:0000823	Delayed puberty
HP:0001009	Telangiectasia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001510	Growth delay
HP:0001531	Failure to thrive in infancy
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001891	Iron deficiency anemia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002187	Profound intellectual disability
HP:0002465	Poor speech
HP:0002665	Lymphoma
HP:0002719	Recurrent infections
HP:0003202	Skeletal muscle atrophy
HP:0003540	Impaired platelet aggregation
HP:0003593	Infantile onset
HP:0003621	Juvenile onset

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004599_37	Mean platelet volume	4.000000e-10
GCST005038_103	Allergic disease (asthma, hay fever or eczema)	6.000000e-11
GCST010002_39	Refractive error	2.000000e-14
GCST010244_167	Triglyceride levels	4.000000e-11
GCST012490_103	Femur bone mineral density x serum urate levels interaction	9.000000e-09
GCST90000050_37	Age at first birth	1.000000e-08
GCST90002395_465	Mean platelet volume	6.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement
EFO:0009101	age at first birth measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D004827	Epilepsy	C10.228.140.490
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D044905	beta-Mannosidosis	C16.320.565.202.607.750; C16.320.565.595.577.750; C18.452.648.202.607.750; C18.452.648.595.577.750
C565121	Deafness, Autosomal Dominant 1 (supp.)
C536648	Pendred syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4295668 (SINGLE PROTEIN), CHEMBL4523648 (PROTEIN COMPLEX)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.28	Kd	5.213	nM	CHEMBL3752910
8.28	ED50	5.213	nM	CHEMBL3752910
5.84	Kd	1440	nM	CHEMBL5653589
5.84	ED50	1440	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148239: Binding affinity to human DIAPH1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0052	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148239: Binding affinity to human DIAPH1 incubated for 45 mins by Kinobead based pull down assay	kd	1.4396	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	4
sodium arsenite	increases expression, decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression, affects expression	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
PCB 180	decreases expression	1
ICG 001	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Dinitrochlorobenzene	affects binding	1
Endosulfan	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119004	Binding	Binding affinity to DIAPH1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1DD	Abcam HCT 116 DIAPH1 KO	Cancer cell line	Male
CVCL_B2VW	Abcam HEK293T DIAPH1 KO	Transformed cell line	Female
CVCL_E1FP	Abcam HEK293 DIAPH1 KO	Transformed cell line	Female
CVCL_SK82	HAP1 DIAPH1 (-) 1	Cancer cell line	Male
CVCL_SK83	HAP1 DIAPH1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
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