DIAPH3 (diaphanous related formin 3)

Gene

• Entrez ID: 81624
• Gene name: Diaphanous related formin 3
• Gene symbol: DIAPH3
• Synonyms (NCBI Gene): AN, AUNA1, DIA2, DRF3, NSDAN, diap3, mDia2
• Chromosome: 13
• Chromosome location: 13q21.2
• Summary: 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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020756	hsa-miR-155-5p	Proteomics	18668040
MIRT935975	hsa-miR-4330	CLIP-seq
MIRT935976	hsa-miR-4643	CLIP-seq
MIRT935977	hsa-miR-4701-5p	CLIP-seq
MIRT935978	hsa-miR-4717-3p	CLIP-seq
MIRT935979	hsa-miR-588	CLIP-seq
MIRT935980	hsa-miR-624	CLIP-seq
MIRT935981	hsa-miR-759	CLIP-seq
MIRT1977012	hsa-miR-142-5p	CLIP-seq
MIRT1977013	hsa-miR-224	CLIP-seq
MIRT1977014	hsa-miR-340	CLIP-seq
MIRT1977015	hsa-miR-4422	CLIP-seq
MIRT935976	hsa-miR-4643	CLIP-seq
MIRT935978	hsa-miR-4717-3p	CLIP-seq
MIRT2212449	hsa-miR-4263	CLIP-seq
MIRT2212450	hsa-miR-4509	CLIP-seq
MIRT2212451	hsa-miR-4744	CLIP-seq
MIRT2212452	hsa-miR-576-5p	CLIP-seq
MIRT1977015	hsa-miR-4422	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000226	Process	Microtubule cytoskeleton organization	IEA
GO:0000813	Component	ESCRT I complex	IEA
GO:0000922	Component	Spindle pole	IEA
GO:0001701	Process	In utero embryonic development	IEA
GO:0003779	Function	Actin binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0005815	Component	Microtubule organizing center	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005884	Component	Actin filament	IBA
GO:0007010	Process	Cytoskeleton organization	IEA
GO:0007010	Process	Cytoskeleton organization	ISS
GO:0007015	Process	Actin filament organization	IEA
GO:0007026	Process	Negative regulation of microtubule depolymerization	IEA
GO:0007059	Process	Chromosome segregation	IEA
GO:0007229	Process	Integrin-mediated signaling pathway	IEA
GO:0007605	Process	Sensory perception of sound	IEA
GO:0008017	Function	Microtubule binding	IEA
GO:0008092	Function	Cytoskeletal protein binding	IEA
GO:0010467	Process	Gene expression	IEA
GO:0016197	Process	Endosomal transport	IEA
GO:0030010	Process	Establishment of cell polarity	IEA
GO:0030030	Process	Cell projection organization	IEA
GO:0030036	Process	Actin cytoskeleton organization	IEA
GO:0030036	Process	Actin cytoskeleton organization	ISS
GO:0030041	Process	Actin filament polymerization	IBA
GO:0030041	Process	Actin filament polymerization	IEA
GO:0030041	Process	Actin filament polymerization	ISS
GO:0030182	Process	Neuron differentiation	IEA
GO:0030218	Process	Erythrocyte differentiation	IEA
GO:0030225	Process	Macrophage differentiation	IEA
GO:0031267	Function	Small GTPase binding	IEA
GO:0031941	Component	Filamentous actin	IEA
GO:0032154	Component	Cleavage furrow	IEA
GO:0032432	Component	Actin filament bundle	IEA
GO:0034367	Process	Protein-containing complex remodeling	IEA
GO:0042803	Function	Protein homodimerization activity	IEA
GO:0043131	Process	Erythrocyte enucleation	IEA
GO:0045010	Process	Actin nucleation	IEA
GO:0045296	Function	Cadherin binding	HDA	25468996
GO:0046785	Process	Microtubule polymerization	IEA
GO:0051017	Process	Actin filament bundle assembly	IEA
GO:0051764	Process	Actin crosslink formation	IEA
GO:0060113	Process	Inner ear receptor cell differentiation	IEA
GO:0060322	Process	Head development	IEA
GO:0061909	Process	Autophagosome-lysosome fusion	IEA
GO:0071800	Process	Podosome assembly	IEA
GO:0097470	Component	Ribbon synapse	IEA
GO:1990427	Component	Stereocilia tip-link density	IEA

Other IDs

• MIM: 614567
• HGNC: 15480
• e!Ensembl: ENSG00000139734

Protein

• UniProt ID: Q9NSV4
• Protein name: Protein diaphanous homolog 3 (Diaphanous-related formin-3) (DRF3) (MDia2)
• Protein 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 t
• PDB: 5UWP, 6X2Y
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06371	Drf_GBD	113 → 297	Diaphanous GTPase-binding Domain	Family
  PF06367	Drf_FH3	302 → 492	Diaphanous FH3 Domain	Family
  PF02181	FH2	636 → 1009	Formin Homology 2 Domain	Family
  PF06345	Drf_DAD	1060 → 1074	DRF Autoregulatory Domain	Motif

• Sequence:

  MERHQPRLHHPAQGSAAGTPYPSSASLRGCRESKMPRRKGPQHPPPPSGPEEPGEKRPKF
  HLNIRTLTDDMLDKFASIRIPGSKKERPPLPNLKTAFASSDCSAAPLEMMENFPKPLSEN
  ELLELFEKMMEDMNLNEDKKAPLREKDFSIKKEMVMQYINTASKTGSLKRSRQISPQEFI
  HELKMGSADERLVTCLESLRVSLTSNPVSWVESFGHEGLGLLLDILEKLISGKIQEKVVK
  KNQHKVIQCLKALMNTQYGLERIMSEERSLSLLAKAVDPRHPNMMTDVVKLLSAVCIVGE
  ESILEEVLEALTSAGEEKKIDRFFCIVEGLRHNSVQLQVACMQLINALVTSPDDLDFRLH
  IRNEFMRCGLKEILPNLKCIKNDGLDIQLKVFDEHKEEDLFELSHRLEDIRAELDEAYDV
  YNMVWSTVKETRAEGYFISILQHLLLIRNDYFIRQQYFKLIDECVSQIVLHRDGMDPDFT
  YRKRLDLDLTQFVDICIDQAKLEEFEEKASELYKKFEKEFTDHQETQAELQKKEAKINEL
  QAELQAFKSQFGALPADCNIPLPPSKEGGTGHSALPPPPPLPSGGGVPPPPPPPPPPPLP
  GMRMPFSGPVPPPPPLGFLGGQNSPPLPILPFGLKPKKEFKPEISMRRLNWLKIRPHEMT
  ENCFWIKVNENKYENVDLLCKLENTFCCQQKERREEEDIEEKKSIKKKIKELKFLDSKIA
  QNLSIFLSSFRVPYEEIRMMILEVDETRLAESMIQNLIKHLPDQEQLNSLSQFKSEYSNL
  CEPEQFVVVMSNVKRLRPRLSAILFKLQFEEQVNNIKPDIMAVSTACEEIKKSKSFSKLL
  ELVLLMGNYMNAGSRNAQTFGFNLSSLCKLKDTKSADQKTTLLHFLVEICEEKYPDILNF
  VDDLEPLDKASKVSVETLEKNLRQMGRQLQQLEKELETFPPPEDLHDKFVTKMSRFVISA
  KEQYETLSKLHENMEKLYQSIIGYYAIDVKKVSVEDFLTDLNNFRTTFMQAIKENIKKRE
  AEEKEKRVRIAKELAERERLERQQKKKRLLEMKTEGDETGVMDNLLEALQSGAAFRDRRK
  RTPMPKDVRQSLSPMSQRPVLKVCNHENQKVQLTEGSRSHYNINCNSTRTPVAKELNYNL
  DTHTSTGRIKAAEKKEACNVESNRKKETELLGSFSKNESVPEVEALLARLRAL

• Sequence length: 1193

Pathways

KEGG:

Regulation of actin cytoskeleton
Cytoskeleton in muscle cells

Reactome:

RHO GTPases Activate Formins

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal dominant auditory neuropathy 1	Pathogenic	rs2050261564	RCV001264612	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANGIOEDEMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Auditory neuropathy	Uncertain significance	ClinVar ClinGen, Disgenet, Orphanet ClinGen, Disgenet, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
AUDITORY NEUROPATHY, AUTOSOMAL DOMINANT 1	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUDITORY NEUROPATHY, AUTOSOMAL DOMINANT, 1	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT ISOLATED SENSORINEURAL DEAFNESS TYPE DFNA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT NONSYNDROMIC HEARING LOSS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILIARY ATRESIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC KIDNEY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEPHROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIAPH3-related disorder	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing impairment	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESTLESS LEGS SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	31586548		★☆☆☆☆ Found in Text Mining only
Apraxias	Apraxia	Pubtator	22738016	Associate	★☆☆☆☆ Found in Text Mining only
Auditory neuropathy	Auditory Neuropathy	BEFREE	20624953, 23441200		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Auditory neuropathy	Auditory Neuropathy	CLINGEN_DG	20624953, 23441200		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Auditory neuropathy spectrum disorder	Auditory neuropathy	BEFREE	20624953, 23441200		★☆☆☆☆ Found in Text Mining only
Auditory neuropathy spectrum disorder	Auditory neuropathy	CLINGEN_DG	20624953, 23441200		★☆☆☆☆ Found in Text Mining only
AUDITORY NEUROPATHY, AUTOSOMAL DOMINANT, 1	Auditory Neuropathy	BEFREE	20624953		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUDITORY NEUROPATHY, AUTOSOMAL DOMINANT, 1	Auditory Neuropathy	GENOMICS_ENGLAND_DG	27658576		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUDITORY NEUROPATHY, AUTOSOMAL DOMINANT, 1	Auditory Neuropathy	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	BEFREE	20308993		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	22738016	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal dominant non-syndromic sensorineural deafness type DFNA	Non-Syndromic Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	26179371		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	26179371	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	31586548		★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	24587343	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	33297976	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	39376176	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	24587343		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	34308980, 34911835	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	35538918	Inhibit	★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	GWASDB_DG	22319020		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL RECESSIVE (disorder)	Deafness	BEFREE	27177047		★☆☆☆☆ Found in Text Mining only
Epilepsy Rolandic	Rolandic epilepsy	Pubtator	22738016	Associate	★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	24587343		★☆☆☆☆ Found in Text Mining only
Epithelioma	Epithelioma	BEFREE	24587343		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	29692731		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	32727404	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	29692731		★☆☆☆☆ Found in Text Mining only
Laryngeal Squamous Cell Carcinoma	Laryngeal Carcinoma	BEFREE	30793164		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28795316		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	26179371		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	31586548		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	24423651, 26179371, 28779705		★☆☆☆☆ Found in Text Mining only
Metastatic Prostate Carcinoma	Metastatic Prostate Carcinoma	BEFREE	24423651		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	35689754	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19549916, 24423651		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	40486509	Associate	★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	24423651, 28779705		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	19549916		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	19549916, 24423651	Associate	★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	26811494	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Cancer Papillary	Papillary thyroid cancer	Pubtator	39376176	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Carcinoma Anaplastic	Thyroid cancer	Pubtator	39376176	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	28779705		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	36750200	Associate	★☆☆☆☆ Found in Text Mining only