DIAPH3

Summary

DIAPH3 (diaphanous related formin 3, HGNC:15480) is a protein-coding gene on chromosome 13q21.2, encoding Protein diaphanous homolog 3 (Q9NSV4). Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers.

This gene encodes a member of the diaphanous subfamily of the formin family. Members of this family are involved in actin remodeling and regulate cell movement and adhesion. Mutations in this gene are associated with autosomal dominant auditory neuropathy 1. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 81624 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nonsyndromic hearing loss (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 683 total — 2 pathogenic, 1 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 23 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 7
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.89 (unconstrained)
• MANE Select transcript: NM_001042517
• Interaction hub: 1,851 STRING partners (top 9% of genes corpus-wide)
• Notable: 683 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15480
Approved symbol	DIAPH3
Name	diaphanous related formin 3
Location	13q21.2
Locus type	gene with protein product
Status	Approved
Aliases	DRF3, FLJ34705, AN, NSDAN
Ensembl gene	ENSG00000139734
Ensembl biotype	protein_coding
OMIM	614567
Entrez	81624

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000400324

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 7, TSL 5: 2

ENST00000400324, ENST00000267215, ENST00000377908, ENST00000400319, ENST00000400320, ENST00000465066, ENST00000470420, ENST00000498416, ENST00000615942, ENST00000649952, ENST00001131695

RefSeq mRNA: 7 — MANE Select: NM_001042517 NM_001042517, NM_001258366, NM_001258367, NM_001258368, NM_001258369, NM_001258370, NM_030932

CCDS: CCDS41898, CCDS58294, CCDS58295, CCDS58296, CCDS58297, CCDS73579, CCDS73580

Canonical transcript exons

ENST00000400324 — 28 exons

Exon	Start	End
ENSE00001475479	59774189	59774248
ENSE00001634806	60132957	60132989
ENSE00001660462	60015913	60015982
ENSE00001668777	60042690	60042820
ENSE00001678802	60016071	60016145
ENSE00001751108	60093628	60093732
ENSE00001806741	60112010	60112186
ENSE00001891196	60163587	60163928
ENSE00001892921	59665583	59666846
ENSE00003540828	60010533	60010669
ENSE00003553861	59861407	59861536
ENSE00003713074	59970852	59971160
ENSE00003715173	60008544	60008649
ENSE00003718160	59991158	59991274
ENSE00003725076	59833107	59833271
ENSE00003725145	59974352	59974456
ENSE00003726046	59774728	59774823
ENSE00003731831	59879229	59879468
ENSE00003733396	59992473	59992583
ENSE00003733540	59810788	59810923
ENSE00003733920	59992068	59992186
ENSE00003737799	59916155	59916249
ENSE00003741322	59983769	59983887
ENSE00003744869	59924775	59924870
ENSE00003747166	59911735	59911836
ENSE00003749783	59839324	59839448
ENSE00003751637	59969944	59970058
ENSE00003752503	59980795	59980859

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 91.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3615 / max 261.8440, expressed in 1440 samples.

Highest expression (Bgee): sperm, ventricular zone, male germ cell, testis, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DIAPH3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 24 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Visceral Omentum	eqtl	1.0e-22	-0.38	13:60085661:T:C
Esophagus Mucosa	eqtl	1.6e-16	-0.26	13:60130237:T:C
Brain Caudate basal ganglia	eqtl	2.9e-10	-0.23	13:59783597:T:C
Brain Frontal Cortex BA9	eqtl	7.5e-09	-0.30	13:59779277:A:T
Skin Sun Exposed Lower leg	eqtl	3.3e-07	-0.16	13:59975593:C:A
Testis	eqtl	1.2e-06	+0.12	13:60111489:T:C
Brain Putamen basal ganglia	eqtl	2.0e-05	-0.25	13:59813852:T:C
Brain Hypothalamus	eqtl	2.7e-05	-0.24	13:59865194:G:A
Brain Anterior cingulate cortex BA24	eqtl	5.9e-05	-0.31	13:59805511:T:A
Brain Nucleus accumbens basal ganglia	eqtl	7.2e-05	-0.21	13:59775326:C:T
Brain Cortex	eqtl	2.0e-04	-0.26	13:59845972:G:A
Brain Amygdala	eqtl	3.7e-04	-0.24	13:59771400:T:G
Testis	sqtl	1.2e-03	-0.79	13:59847749:A:G
Pancreas	eqtl	2.3e-03	-1.00	13:60598570:A:C
Brain Hippocampus	eqtl	6.7e-03	-0.21	13:59814404:C:G
Cells EBV-transformed lymphocytes	eqtl	7.0e-03	-0.42	13:60086348:C:T
Adipose Subcutaneous	eqtl	8.3e-03	-0.67	13:60270240:T:C
Artery Aorta	eqtl	1.2e-02	-0.36	13:59800162:C:T
Brain Substantia nigra	eqtl	1.8e-02	-0.27	13:59715178:T:A
Artery Tibial	eqtl	1.9e-02	-0.11	13:60098933:A:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
137465	14.3230	1411
137464	1.3254	555
137463	0.3856	216
137462	0.3141	168
137460	0.0134	3

Top tissues by expression

showing 100 of 273 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	91.48	gold quality
ventricular zone	UBERON:0003053	90.46	gold quality
male germ cell	CL:0000015	87.91	gold quality
left testis	UBERON:0004533	84.80	gold quality
right testis	UBERON:0004534	84.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.34	gold quality
testis	UBERON:0000473	84.00	gold quality
secondary oocyte	CL:0000655	83.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.32	gold quality
ganglionic eminence	UBERON:0004023	82.78	gold quality
stromal cell of endometrium	CL:0002255	79.71	gold quality
buccal mucosa cell	CL:0002336	78.84	gold quality
trabecular bone tissue	UBERON:0002483	77.66	gold quality
oocyte	CL:0000023	76.93	gold quality
esophagus squamous epithelium	UBERON:0006920	76.33	gold quality
parietal pleura	UBERON:0002400	75.80	gold quality
cartilage tissue	UBERON:0002418	74.75	gold quality
tibia	UBERON:0000979	74.59	gold quality
placenta	UBERON:0001987	73.49	gold quality
oral cavity	UBERON:0000167	72.35	silver quality
epithelium of esophagus	UBERON:0001976	72.27	gold quality
adrenal tissue	UBERON:0018303	72.11	gold quality
pleura	UBERON:0000977	71.68	gold quality
bone marrow	UBERON:0002371	71.54	gold quality
amniotic fluid	UBERON:0000173	70.93	gold quality
caudate nucleus	UBERON:0001873	70.62	gold quality
anterior cingulate cortex	UBERON:0009835	70.22	gold quality
cingulate cortex	UBERON:0003027	70.15	gold quality
ascending aorta	UBERON:0001496	70.09	gold quality
mucosa of transverse colon	UBERON:0004991	70.00	gold quality
nucleus accumbens	UBERON:0001882	69.97	gold quality
lower esophagus mucosa	UBERON:0035834	69.81	gold quality
esophagus mucosa	UBERON:0002469	69.74	gold quality
thoracic aorta	UBERON:0001515	69.71	gold quality
embryo	UBERON:0000922	69.54	gold quality
amygdala	UBERON:0001876	69.33	gold quality
rectum	UBERON:0001052	69.07	gold quality
duodenum	UBERON:0002114	69.07	gold quality
colonic mucosa	UBERON:0000317	69.04	gold quality
body of stomach	UBERON:0001161	69.02	gold quality
squamous epithelium	UBERON:0006914	68.83	silver quality
stomach	UBERON:0000945	68.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	68.35	gold quality
putamen	UBERON:0001874	67.61	gold quality
vermiform appendix	UBERON:0001154	67.09	gold quality
visceral pleura	UBERON:0002401	66.58	gold quality
upper leg skin	UBERON:0004262	66.36	gold quality
endometrium	UBERON:0001295	66.07	gold quality
germinal epithelium of ovary	UBERON:0001304	65.99	gold quality
bone marrow cell	CL:0002092	65.55	silver quality
smooth muscle tissue	UBERON:0001135	65.47	gold quality
prefrontal cortex	UBERON:0000451	65.30	gold quality
telencephalon	UBERON:0001893	65.27	gold quality
right coronary artery	UBERON:0001625	65.18	gold quality
temporal lobe	UBERON:0001871	65.11	gold quality
lateral globus pallidus	UBERON:0002476	65.11	silver quality
medial globus pallidus	UBERON:0002477	65.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.01	gold quality
aorta	UBERON:0000947	64.91	gold quality
skin of hip	UBERON:0001554	64.81	gold quality
gingiva	UBERON:0001828	64.80	silver quality
pigmented layer of retina	UBERON:0001782	64.56	gold quality
colonic epithelium	UBERON:0000397	64.50	silver quality
neocortex	UBERON:0001950	64.48	gold quality
gingival epithelium	UBERON:0001949	64.32	silver quality
hypothalamus	UBERON:0001898	64.12	gold quality
cerebral cortex	UBERON:0000956	64.03	gold quality
lymph node	UBERON:0000029	64.00	gold quality
Ammon’s horn	UBERON:0001954	63.58	gold quality
globus pallidus	UBERON:0001875	63.38	gold quality
jejunal mucosa	UBERON:0000399	63.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	63.26	gold quality
right lung	UBERON:0002167	63.07	gold quality
cortical plate	UBERON:0005343	63.06	gold quality
frontal cortex	UBERON:0001870	62.96	gold quality
forebrain	UBERON:0001890	62.96	gold quality
metanephros	UBERON:0000081	62.72	gold quality
caecum	UBERON:0001153	62.70	gold quality
descending thoracic aorta	UBERON:0002345	62.70	gold quality
right frontal lobe	UBERON:0002810	62.50	gold quality
fundus of stomach	UBERON:0001160	61.93	gold quality
endothelial cell	CL:0000115	61.62	gold quality
entorhinal cortex	UBERON:0002728	61.50	gold quality
tibial artery	UBERON:0007610	61.49	gold quality
popliteal artery	UBERON:0002250	61.45	gold quality
substantia nigra	UBERON:0002038	61.40	gold quality
ileal mucosa	UBERON:0000331	61.28	silver quality
upper lobe of lung	UBERON:0008948	61.03	gold quality
metanephros cortex	UBERON:0010533	60.79	gold quality
brain	UBERON:0000955	60.78	gold quality
lung	UBERON:0002048	60.69	gold quality
upper lobe of left lung	UBERON:0008952	60.50	gold quality
skin of abdomen	UBERON:0001416	60.40	gold quality
lower lobe of lung	UBERON:0008949	60.36	silver quality
tonsil	UBERON:0002372	60.27	gold quality
esophagus	UBERON:0001043	60.22	gold quality
left coronary artery	UBERON:0001626	59.80	gold quality
midbrain	UBERON:0001891	59.67	gold quality
superior frontal gyrus	UBERON:0002661	59.64	gold quality
corpus callosum	UBERON:0002336	59.34	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	725.97
E-MTAB-11268	yes	632.36
E-MTAB-6678	yes	9.60
E-ANND-3	yes	6.29
E-CURD-119	no	743.28
E-MTAB-7249	no	370.14

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 70 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Testis	tissue	17.7
Bone marrow	tissue	6.7
Cerebellum	tissue	6.5
Cerebral cortex	tissue	5.8
Retrosplenial and cingulate cortex	tissue	5.8
Olfactory bulb	tissue	5.4
Retrosplenial cortex	tissue	5.4
Thymus	tissue	5.0
Amygdala	tissue	4.6
Insular cortex	tissue	4.3
Prefrontal cortex	tissue	4.2
Hippocampal formation	tissue	4.1
Entorhinal cortex	tissue	4.1
Basal ganglia	tissue	4.0
Temporal cortex	tissue	4.0
Corpus callosum	tissue	3.9
Occipital cortex	tissue	3.9
Frontal cortex	tissue	3.8
Motor cortex	tissue	3.7
Ventral forebrain	tissue	3.5
Caudate putamen	tissue	3.5
Septum	tissue	3.4
Placenta	tissue	3.3
Periaqueductal gray	tissue	3.3
Somatosensory cortex	tissue	3.2
Putamen	tissue	3.1
Hypothalamus	tissue	2.9
Smooth muscle	tissue	2.4
Medulla oblongata	tissue	2.4
Thalamus	tissue	2.4
Substantia nigra	tissue	2.4
Spinal cord	tissue	2.4
Midbrain	tissue	2.3
Tonsil	tissue	2.3
Lymph node	tissue	2.2
Rectum	tissue	1.9
Superior colliculi	tissue	1.9
Pons	tissue	1.8
Duodenum	tissue	1.8
Colon	tissue	1.7
Esophagus	tissue	1.6
Appendix	tissue	1.6
Stomach 1	tissue	1.5
Small intestine	tissue	1.5
Skin 1	tissue	1.2
Lung	tissue	1.1
Kidney	tissue	0.8
Breast	tissue	0.7
Vagina	tissue	0.7
Ovary	tissue	0.6
Urinary bladder	tissue	0.6
Endometrium 1	tissue	0.5
Adipose tissue	tissue	0.4
Choroid plexus	tissue	0.4
Spleen	tissue	0.4
Gallbladder	tissue	0.4
Cervix	tissue	0.3
Salivary gland	tissue	0.2
Pancreas	tissue	0.2
Liver	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 176; highest nTPM — Ventral hippocampus (4.0), Dorsal hippocampus (3.9), White matter (3.9), Subiculum (3.8), Dorsal spinal cord (2.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DIAPH3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 95 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Functional genomics

gnomAD constraint: pLI 5.87e-21, LOEUF 0.889, missense Z 0.641 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000400324 — one region, missense o/e 1.01.

Literature-anchored findings (GeneRIF, showing 31)

• These studies further suggest that Rho GTPases significantly influence the activity of mDia family formins in driving cellular membrane remodeling through the regulation of actin dynamics. (PMID:17198702)
• DIP-induced membrane blebbing was dependent on Diaphanous 2 but did not require the activities of either Diaphanous 1 or Actin-Related Protein 2-3 Complex. (PMID:17398099)
• Data show that Dia2 localizes in the lamella of migrating epithelial cells, where it is involved in the formation of a stable pool of cortical actin and in maintenance of polymerization-competent free filament barbed ends at focal adhesions. (PMID:17855386)
• Results suggest that WAVE and the Arp2/3 complex jointly orchestrate different types of actin-based plasma membrane protrusions by promoting ruffling and inhibiting mDia2-induced filopodia. (PMID:18516090)
• active Drf3 lacking the C-terminal regulatory region (Drf3DeltaDAD) induced the formation of filopodia and accumulated at their tips. (PMID:18755006)
• mDia2 is degraded at the end of mitosis; mDia2 is targeted for disposal by post-translational ubiquitin modification; forced expression of activated mDia2 yields binucleate cells due to failed cytokinesis (PMID:19457867)
• the amino terminus of mDia2 serves as a coincidence detection module, directing mDia2 to the plasma membrane through interactions with phospholipids and activated Rif (PMID:21119010)
• These findings reveal a key role for mDia3 and its regulation by Aurora B phosphorylation in achieving proper stable kinetochore microtubule attachment. (PMID:21397845)
• isoform-selective actin assembly by DIAPH3 exerts specific and differentially regulated functions during cell adhesion and motility. (PMID:22184005)
• In human tumours, DIAPH3 down-regulation was associated with aggressive or metastatic disease. (PMID:22593025)
• TGF-beta promotes association of mDia2 with actin stress fibers, which further drives stress fiber formation and myofibroblast differentiation (PMID:23580645)
• Dia1, Dia2, and Dia3 are involved in ErbB2-dependent capture of microtubules at the cell leading edge and ErbB2-driven guided migration. (PMID:24403606)
• An mDia2/ROCK signaling axis regulates invasive egress from epithelial ovarian cancer spheroids. (PMID:24587343)
• results suggest that inhibition of MT stability arising from DIAPH3 downregulation enhances susceptibility to MT poisons, and that the DIAPH3 network potentially reports taxane sensitivity in human tumors (PMID:26179371)
• we use a simple cellular system to examine fundamental features of formin-mediated filopodial assembly, using constitutively active constructs of the formins mDia2 and FMNL3 (PMID:26446836)
• Members of 3 generations of a family had dominant auditory neuropathy associated with a c.-172G>A point mutation in DIAPH3. (PMID:27658576)
• These data identify Diaph3 as a major guard of cortical progenitors, unravel novel functions of Diaphanous formins and add insights into the pathobiology of microcephaly. (PMID:27848932)
• mDia2 and CXCR4 associate in blebs upon CXCL12 stimulation. Both CXCR4 and RhoA are required for CXCL12-induced blebbing (PMID:28115158)
• DIAPH3 overexpression inhibits the migration and invasion of Triple-negative breast cancer by inhibiting RhoA-GTP expression. (PMID:28779705)
• study demonstrated the oncogenic activity of DIAPH3 in the progression of hepatocellular carcinoma and suggested that PDIAPH3 might be a therapeutic target. (PMID:28795316)
• through profilin-1 binding, CLIC4 functions in a RhoA-mDia2-regulated signaling network to integrate cortical actin assembly and membrane protrusion (PMID:30381396)
• Tropomyosin concentration but not formin nucleators mDia1 and mDia3 determines the level of tropomyosin incorporation into actin filaments. (PMID:31019238)
• The oncogenic roles of DIAPH3 in the tumorigenesis of lung cance. (PMID:31586548)
• Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model. (PMID:33297976)
• DIAPH3 promotes pancreatic cancer progression by activating selenoprotein TrxR1-mediated antioxidant effects. (PMID:33345387)
• Diaph3 underlines tumor cell heterogeneity in glioblastoma with implications for treatment modalities resistance. (PMID:35380294)
• DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation. (PMID:35538918)
• DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling. (PMID:36640348)
• The pan-cancer analysis identified DIAPH3 as a diagnostic biomarker of clinical cancer. (PMID:36750200)
• Super Enhancer-Regulated LncRNA LINC01089 Induces Alternative Splicing of DIAPH3 to Drive Hepatocellular Carcinoma Metastasis. (PMID:37756562)
• CircDiaph3 aggravates H/R-induced cardiomyocyte apoptosis and inflammation through miR-338-3p/SRSF1 axis. (PMID:38613636)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	diaph3	ENSDARG00000090785
mus_musculus	Diaph3	ENSMUSG00000022021
rattus_norvegicus	Diaph3	ENSRNOG00000008986
caenorhabditis_elegans		WBGENE00018976

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), FHDC1 (ENSG00000137460), DAAM2 (ENSG00000146122), DIAPH2 (ENSG00000147202), FMN2 (ENSG00000155816), FMNL2 (ENSG00000157827), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485), GRID2IP (ENSG00000215045)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1927222) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 36 distinct phenotype terms.

Mouse phenotype (MP)	Records
extramedullary hematopoiesis	2
embryonic lethality during organogenesis, complete penetrance	2
decreased hematocrit	1
abnormal pericardium morphology	1
abnormal craniofacial morphology	1
enlarged spleen	1
anemia	1
abnormal embryo size	1
decreased embryo size	1
abnormal embryo turning	1
premature death	1
abnormal cardiovascular system morphology	1
mydriasis	1
decreased mean corpuscular volume	1
anisopoikilocytosis	1
decreased circulating triglyceride level	1
decreased circulating free fatty acids level	1
decreased hemoglobin content	1
decreased erythrocyte cell number	1
abnormal cell cycle	1
pallor	1
embryonic growth retardation	1
abnormal inner hair cell stereociliary bundle morphology	1
decreased inner hair cell stereocilia number	1
abnormal inner hair cell synaptic ribbon morphology	1

+11 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Arabidopsis thaliana	Q9SE97	72.2%	Diamond
Oryza sativa Japonica Group	Q6MWG9	64.6%	Diamond
Drosophila melanogaster	P48608	41.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC00434	ncRNA	100874169
DIAPH3-AS2	ncRNA	100874196
DIAPH3-AS1	ncRNA	100874195

Protein

Protein identifiers

Protein diaphanous homolog 3 — Q9NSV4 (reviewed: Q9NSV4)

Alternative names: Diaphanous-related formin-3, MDia2

All UniProt accessions (1): Q9NSV4

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. Required for cytokinesis, stress fiber formation and transcriptional activation of the serum response factor. Binds to GTP-bound form of Rho and to profilin: acts in a Rho-dependent manner to recruit profilin to the membrane, where it promotes actin polymerization. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. 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.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Ubiquitinated.

Disease relevance. Auditory neuropathy, autosomal dominant 1 (AUNA1) [MIM:609129] A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. Affected individuals typically respond to sound but have difficulties in speech discrimination. The disease is caused by variants affecting the gene represented in this entry. A disease-causing mutation in the conserved 5’-UTR leads to increased protein expression.

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 (7)

UniProt ID	Names	Canonical?
Q9NSV4-3	3	yes
Q9NSV4-1	1
Q9NSV4-2	2
Q9NSV4-4	4
Q9NSV4-5	5
Q9NSV4-6	6
Q9NSV4-7	7

RefSeq proteins (7): NP_001035982, NP_001245295, NP_001245296, NP_001245297, NP_001245298, NP_001245299, NP_112194 (=MANE)

Domains & families (InterPro)

ID	Name	Type
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

Pfam: PF02181, PF06367, PF06371

UniProt features (39 total): splice variant 8, modified residue 7, sequence conflict 7, domain 4, sequence variant 3, short sequence motif 2, compositionally biased region 2, region of interest 2, coiled-coil region 2, chain 1, helix 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
5UWP	Crystal Structure of mDia2 NES Peptide in complex with CRM1-Ran-RanBP1	X-RAY DIFFRACTION	2.05
6X2Y	Crystal Structure of mDia2NES peptide bound to CRM1(E571K)	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSV4-F1	72.33	0.30

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Human disease related genes, Ear disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): microtubules; plasma membrane

Antibody reliability (HPA): IF supported

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 (7)

Type	Positions
Phosphoserine	26, 77, 175, 624, 1093, 1179
Phosphothreonine	68

Function

Pathways and Gene Ontology

Reactome pathways

13 curated (TAS) of 18; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

18 pathways:

ID	Pathway	Evidence
R-HSA-9013148	CDC42 GTPase cycle	curated
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-9013404	RAC2 GTPase cycle	curated
R-HSA-9013423	RAC3 GTPase cycle	curated
R-HSA-5663220	RHO GTPases Activate Formins	curated
R-HSA-8980692	RHOA GTPase cycle	curated
R-HSA-9013026	RHOB GTPase cycle	curated
R-HSA-9013106	RHOC GTPase cycle	curated
R-HSA-9013405	RHOD GTPase cycle	curated
R-HSA-9035034	RHOF GTPase cycle	curated
R-HSA-9013408	RHOG GTPase cycle	curated
R-HSA-9013409	RHOJ GTPase cycle	curated
R-HSA-9013406	RHOQ GTPase cycle	curated
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

MSigDB gene sets: 349 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, chr13q21, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_VESICLE_ORGANIZATION, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (4): cytoskeleton organization (GO:0007010), actin cytoskeleton organization (GO:0030036), actin filament polymerization (GO:0030041), cellular component organization (GO:0016043)

GO Molecular Function (6): actin binding (GO:0003779), microtubule binding (GO:0008017), small GTPase binding (GO:0031267), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (14): ESCRT I complex (GO:0000813), spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), filamentous actin (GO:0031941), cleavage furrow (GO:0032154), actin filament bundle (GO:0032432), ribbon synapse (GO:0097470), stereocilia tip-link density (GO:1990427)

Reactome top-level categories

5 top-level categories:

Category	Pathways
RHO GTPase cycle	12
Signaling by Rho GTPases	2
RHO GTPase Effectors	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signal Transduction	1

GO top-level categories

35 GO namespaces:

Category	Terms
cellular anatomical structure	6
actin cytoskeleton	2
actin filament	2
organelle organization	1
cytoskeleton organization	1
actin filament-based process	1
actin polymerization or depolymerization	1
protein polymerization	1
cellular component organization or biogenesis	1
cytoskeletal protein binding	1
tubulin binding	1
GTPase binding	1
identical protein binding	1
protein dimerization activity	1
cell adhesion molecule binding	1
protein binding	1
endosome membrane	1
ESCRT complex	1
membrane protein complex	1
spindle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoplasm	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
cytoskeleton	1
protein-containing complex	1
cell division site	1
plasma membrane region	1
synapse	1
synaptic ribbon	1
stereocilia tip link	1
cell projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
microtubule cytoskeleton	CC	direct assay
plasma membrane	CC	direct assay
cadherin binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,851 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIAPH3	BLVRB	P30043	832
DIAPH3	BLVRA	P53004	830
DIAPH3	PFN4	Q8NHR9	722
DIAPH3	PFN3	P60673	682
DIAPH3	CDC34	P49427	664
DIAPH3	FBXW7	Q969H0	643
DIAPH3	PFN1	P07737	640
DIAPH3	HEY1	Q9Y5J3	638
DIAPH3	ANLN	Q9NQW6	637
DIAPH3	TRIM3	O75382	630
DIAPH3	RHOA	P06749	606
DIAPH3	WASL	O00401	598
DIAPH3	CDC42	P21181	581
DIAPH3	PJVK	Q0ZLH3	576
DIAPH3	WAS	P42768	571

IntAct

Human interaction partners of DIAPH3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
PGRMC1	physical association	0.400	1
SMAD9	physical association	0.370	1
MYC	physical association	0.000	1

BioGRID (162 interactions; top human partners by supporting records): CCDC183 (Affinity Capture-MS; 3 records), CDC42 (Affinity Capture-MS; 3 records), COMTD1 (Affinity Capture-MS; 3 records), ENPP6 (Affinity Capture-MS; 3 records), HS2ST1 (Affinity Capture-MS; 3 records), NCKIPSD (Two-hybrid; 3 records), RAC1 (Affinity Capture-MS; 3 records), RHOA (Affinity Capture-MS; 3 records), SCN2B (Affinity Capture-MS; 3 records), TPTE2 (Affinity Capture-MS; 3 records), ATG16L1 (Proximity Label-MS; 2 records), BCHE (Affinity Capture-MS; 2 records), EPHA1 (Affinity Capture-MS; 2 records), PCM1 (Proximity Label-MS; 2 records), PNKD (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for DIAPH3: 683 ClinVar records (3 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 15 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	363
Likely benign	203
Benign	51

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
625742	GRCh37/hg19 13q21.1-21.32(chr13:59424409-65723208)	Pathogenic	criteria provided, single submitter	1
4876226	NC_000013.11:g.60163812_60163982delinsTTCTT	Likely pathogenic	criteria provided, single submitter	1
984530	NM_001042517.2(DIAPH3):c.2059del (p.Cys687fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore DIAPH3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 3,743):

Position(s)	Effect	Δscore	Sites
13:59696079	donor_gain	1.0000
13:59774824–59774826	acceptor_gain	1.0000	2
13:59774824–59774825	acceptor_loss	1.0000	5
13:59810786–59810787	donor_loss	1.0000	5
13:59810924–59810925	acceptor_loss	1.0000	6
13:59861405–59861406	donor_loss	1.0000	5
13:59861537–59861538	acceptor_loss	1.0000	6
13:59861548	acceptor_gain	1.0000
13:59881413	acceptor_gain	1.0000
13:59916153–59916154	donor_loss	1.0000	6

AlphaMissense

1,570 missense substitutions predicted likely pathogenic (of 7,950 scored), across 459 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M154	9	0.916	0.992
M129	9	0.894	0.991
F1075	8	0.979	0.998
D399	8	0.958	0.988
N851	8	0.953	0.992
D1063	8	0.952	0.989
N255	8	0.949	0.991
F392	8	0.930	0.988
N848	8	0.930	0.992
F786	8	0.927	0.990
F214	8	0.925	0.986
F126	8	0.923	0.975
N346	8	0.918	0.995
F686	8	0.918	0.988
D132	8	0.913	0.979
D476	8	0.897	0.955
D947	8	0.886	0.956
H360	8	0.885	0.979
D450	8	0.855	0.933
M1062	8	0.852	0.973

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	1.52e-07
Lung Adenocarcinoma (TCGA)	unfavorable	6.38e-05
Lung Adenocarcinoma (validation)	unfavorable	6.75e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	6.87e-05
Kidney Chromophobe (TCGA)	unfavorable	7.37e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000305

Disease associations

OMIM: gene MIM:614567 | disease phenotypes: MIM:609129

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
autosomal dominant auditory neuropathy 1	Limited	Autosomal dominant	3
auditory neuropathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
auditory neuropathy	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Auditory Neuropathy Spectrum Disorde	amber
Monogenic hearing loss	amber
Paediatric disorders	amber

Mondo (3): autosomal dominant auditory neuropathy 1 (MONDO:0012196), auditory neuropathy (MONDO:0021944), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (1): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

7 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001963	Abnormal speech discrimination
HP:0003621	Juvenile onset
HP:0006958	Abnormal auditory evoked potentials
HP:0008529	Absence of acoustic reflex
HP:0011462	Young adult onset

GWAS associations

15 associations:

Study	Trait	p-value
GCST007335_25	Age at first sexual intercourse	6e-15
GCST90000047_223	Age at first sexual intercourse	9e-13
GCST007576_317	Chronotype	1e-12
GCST007576_142	Chronotype	3e-12
GCST007325_55	General risk tolerance (MTAG)	3e-11
GCST007326_32	Number of sexual partners	2e-9
GCST005586_7	Breast milk fatty acid composition (maternal genotype effect)	5e-9
GCST004904_158	Body mass index	1e-8
GCST007327_121	Smoking status (ever vs never smokers)	2e-8
GCST003854_22	Gut microbiota (functional units)	3e-8
GCST011703_16	Smoking initiation	4e-8
GCST010170_1	Neonatal total 25-hydroxyvitamin D levels (maternal genetic effect)	7e-8
GCST010724_27	HOMA-B (corrected for HOMA-IR)	3e-7
GCST005587_6	Breast milk fatty acid composition (infant genotype effect)	5e-7
GCST009391_488	Metabolite levels	5e-7

EFO canonical traits (from GWAS)

11 canonical traits:

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004340	body mass index
EFO:0005939	parental genotype effect measurement
EFO:0007959	fetal genotype effect measurement
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0009749	age at first sexual intercourse measurement
EFO:0008328	chronotype measurement
EFO:0005001	phenylalanine measurement
EFO:0004469	HOMA-B
EFO:0005670	smoking initiation

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C563790	Auditory Neuropathy, Autosomal Dominant, 1 *(supp.)*
C538268	Auditory neuropathy *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs77876672	Efficacy	3	hydrochlorothiazide	Essential hypertension

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs77876672	DIAPH3	3	0.00	1	hydrochlorothiazide

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	5
bisphenol A	decreases expression, increases methylation	2
sodium arsenite	increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
chromium hexavalent ion	increases abundance, decreases expression	2
bisphenol S	decreases methylation, affects cotreatment, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Silicon Dioxide	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Valproic Acid	affects expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
fluorene-9-bisphenol	increases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
sparstolonin B	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1VP	HAP1 DIAPH3 (-) 1	Cancer cell line	Male
CVCL_E1VQ	HAP1 DIAPH3 (-) 2	Cancer cell line	Male
CVCL_E1VR	HAP1 DIAPH3 (-) 3	Cancer cell line	Male
CVCL_E1VS	HAP1 DIAPH3 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 305 trials:

NCT	Phase	Status	Title
NCT00205881	Phase 4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	Phase 4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	Phase 4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	Phase 4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	Phase 4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	Phase 3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	Phase 3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	Phase 3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	Phase 3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	Phase 2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	Phase 2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	Phase 2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	Phase 2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	Phase 2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	Phase 2	WITHDRAWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	Phase 2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	Phase 2	UNKNOWN	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	Phase 2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	Phase 2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	Phase 2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	Phase 2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	Phase 1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	Phase 1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	Phase 1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	Phase 1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	Phase 1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	Phase 1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	Phase 1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	Phase 1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	Phase 1	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
NCT07032038	Phase 1/2	NOT_YET_RECRUITING	First In Human Randomised Trial of Rincell-1 in Adults With a Cochlear Implant
NCT01023932	Not specified	COMPLETED	Auditory Neuropathy and Cochlear Implants
NCT05666466	Not specified	UNKNOWN	Noninvasive Diagnostic Techniques in Determination of Site of Lesion of Auditory Neuropathy Spectrum Disorder
NCT06125015	Not specified	COMPLETED	Unexpected ABR Results in Patients Suspected With Auditory Neuropathy Spectrum Disorder
NCT07778641	Not specified	NOT_YET_RECRUITING	Genetic Study of OTOF- Related Auditory Neuropathy Spectrum Disorder
NCT00486577	Phase 2/3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	Phase 2/3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	Phase 2/3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	Phase 2/3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	Phase 1/2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	Phase 1/2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	Phase 1/2	ACTIVE_NOT_RECRUITING	A Phase I/II Clinical Trial With SENS-501 in Children Suffering From Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	Phase 1/2	ACTIVE_NOT_RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	Phase 1/2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	Early Phase 1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss
NCT03300687	Early Phase 1	COMPLETED	First in Human Safety Study of FX-322 in Adults Undergoing Cochlear Implantation
NCT04777669	Early Phase 1	UNKNOWN	Removing Background Talker Noise for Cochlear Implant Users
NCT06025032	Early Phase 1	WITHDRAWN	a Study in Subjects With Otoferlin Mutation-related Hearing Loss Using RNA Base-eDiting Therapy(SOUND)
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NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00018486	Not specified	COMPLETED	Epidemiology of Hearing Loss in Diabetic and Non-Diabetic Veterans
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT00110604	Not specified	COMPLETED	The Effect of Folic Acid on Atherosclerosis, Cognitive Performance and Hearing
NCT00126113	Not specified	COMPLETED	The Performance-Perceptual Test as a Counseling Tool
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NCT00371449	Not specified	COMPLETED	Predicting Success With Hearing Aids
NCT00371839	Not specified	COMPLETED	Clinical Applications for Time-Compressed Speech Tests