DIAPH1 (diaphanous related formin 1)

Gene

• Entrez ID: 1729
• Gene name: Diaphanous related formin 1
• Gene symbol: DIAPH1
• Synonyms: DFNA1, DIA1, DRF1, LFHL1, SCBMS, hDIA1
• Chromosome: 5
• Chromosome location: 5q31.3
• Summary: 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. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs182139018	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs189809247	C>A,T	Likely-benign, conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs193036129	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign, benign	Missense variant, coding sequence variant
rs200606811	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs367786290	T>A,C	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs369494682	G>A,T	Likely-benign, likely-pathogenic, uncertain-significance	Coding sequence variant, synonymous variant, stop gained
rs730882242	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained
rs863225242	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs863225243	G>A	Pathogenic	Coding sequence variant, stop gained
rs876657776	G>A	Pathogenic	Coding sequence variant, stop gained
rs1057524293	G>A	Pathogenic	Stop gained, coding sequence variant
rs1064794044	GC>A	Pathogenic	Coding sequence variant, frameshift variant
rs1064797096	CT>-	Pathogenic	Coding sequence variant, frameshift variant
rs1235751512	->T	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1476157529	C>A,T	Pathogenic	Splice donor variant
rs1554201397	->TT	Pathogenic	Coding sequence variant, frameshift variant
rs1596335566	TG>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1596339533	A>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1596421912	->A	Likely-pathogenic	Upstream transcript variant, coding sequence variant, genic upstream transcript variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT032344	hsa-let-7b-5p	Proteomics	18668040
MIRT032344	hsa-let-7b-5p	CLASH	23622248
MIRT039957	hsa-miR-615-3p	CLASH	23622248
MIRT043807	hsa-miR-328-3p	CLASH	23622248
MIRT044627	hsa-miR-320a	CLASH	23622248
MIRT045342	hsa-miR-185-5p	CLASH	23622248
MIRT046188	hsa-miR-27b-3p	CLASH	23622248
MIRT046300	hsa-miR-23b-3p	CLASH	23622248
MIRT049688	hsa-miR-92a-3p	CLASH	23622248
MIRT050684	hsa-miR-18a-5p	CLASH	23622248
MIRT051524	hsa-let-7e-5p	CLASH	23622248
MIRT312255	hsa-miR-7110-3p	HITS-CLIP	23824327
MIRT624142	hsa-miR-2355-3p	HITS-CLIP	23824327
MIRT624143	hsa-miR-4646-3p	HITS-CLIP	23824327
MIRT624144	hsa-miR-4433b-5p	HITS-CLIP	23824327
MIRT624145	hsa-miR-4753-3p	HITS-CLIP	23824327
MIRT624146	hsa-miR-6873-3p	HITS-CLIP	23824327
MIRT624147	hsa-miR-130b-5p	HITS-CLIP	23824327
MIRT624148	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT624149	hsa-miR-342-3p	HITS-CLIP	23824327
MIRT624150	hsa-miR-6769b-3p	HITS-CLIP	23824327
MIRT624151	hsa-miR-4723-3p	HITS-CLIP	23824327
MIRT624152	hsa-miR-3183	HITS-CLIP	23824327
MIRT624153	hsa-miR-1228-3p	HITS-CLIP	23824327
MIRT624154	hsa-miR-6800-3p	HITS-CLIP	23824327
MIRT658997	hsa-miR-3674	HITS-CLIP	23824327
MIRT658998	hsa-miR-502-5p	HITS-CLIP	23824327
MIRT658999	hsa-miR-2467-5p	HITS-CLIP	23824327
MIRT659000	hsa-miR-2116-3p	HITS-CLIP	23824327
MIRT659001	hsa-miR-4459	HITS-CLIP	23824327
MIRT659002	hsa-miR-4695-5p	HITS-CLIP	23824327
MIRT659003	hsa-miR-1306-5p	HITS-CLIP	23824327
MIRT735862	hsa-miR-1178-5p	PAR-CLIP	26701625
MIRT736234	hsa-miR-1233-5p	PAR-CLIP	26701625
MIRT736946	hsa-miR-127-5p	PAR-CLIP	26701625
MIRT737149	hsa-miR-1293	PAR-CLIP	26701625
MIRT737936	hsa-miR-15a-5p	PAR-CLIP	26701625
MIRT737958	hsa-miR-15b-5p	PAR-CLIP	26701625
MIRT737985	hsa-miR-16-5p	PAR-CLIP	26701625
MIRT738625	hsa-miR-195-5p	PAR-CLIP	26701625
MIRT738669	hsa-miR-1972	PAR-CLIP	26701625
MIRT739126	hsa-miR-2278	PAR-CLIP	26701625
MIRT739530	hsa-miR-297	PAR-CLIP	26701625
MIRT742149	hsa-miR-3677-5p	PAR-CLIP	26701625
MIRT743057	hsa-miR-3928-5p	PAR-CLIP	26701625
MIRT743167	hsa-miR-3944-5p	PAR-CLIP	26701625
MIRT743298	hsa-miR-424-5p	PAR-CLIP	26701625
MIRT745146	hsa-miR-4483	PAR-CLIP	26701625
MIRT745496	hsa-miR-4501	PAR-CLIP	26701625
MIRT745878	hsa-miR-4524b-3p	PAR-CLIP	26701625
MIRT747070	hsa-miR-4690-5p	PAR-CLIP	26701625
MIRT747305	hsa-miR-4701-5p	PAR-CLIP	26701625
MIRT749279	hsa-miR-497-5p	PAR-CLIP	26701625
MIRT749298	hsa-miR-4999-5p	PAR-CLIP	26701625
MIRT750365	hsa-miR-541-3p	PAR-CLIP	26701625
MIRT751124	hsa-miR-567	PAR-CLIP	26701625
MIRT751552	hsa-miR-588	PAR-CLIP	26701625
MIRT753436	hsa-miR-654-5p	PAR-CLIP	26701625
MIRT755181	hsa-miR-6769a-5p	PAR-CLIP	26701625
MIRT755227	hsa-miR-6769b-5p	PAR-CLIP	26701625
MIRT755430	hsa-miR-6778-5p	PAR-CLIP	26701625
MIRT756495	hsa-miR-6806-3p	PAR-CLIP	26701625
MIRT756919	hsa-miR-6823-5p	PAR-CLIP	26701625
MIRT757280	hsa-miR-6838-5p	PAR-CLIP	26701625
MIRT760550	hsa-miR-92a-2-5p	PAR-CLIP	26701625

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003723	Function	RNA binding	HDA	22658674
GO:0003779	Function	Actin binding	IEA
GO:0005102	Function	Signaling receptor binding	NAS	9360932
GO:0005515	Function	Protein binding	IPI	18218625, 18230650, 18922799, 22190034
GO:0005634	Component	Nucleus	ISS
GO:0005737	Component	Cytoplasm	ISS
GO:0005815	Component	Microtubule organizing center	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	TAS
GO:0007010	Process	Cytoskeleton organization	IMP	21834987
GO:0007010	Process	Cytoskeleton organization	ISS
GO:0007605	Process	Sensory perception of sound	IEA
GO:0008360	Process	Regulation of cell shape	IMP	21834987
GO:0030036	Process	Actin cytoskeleton organization	ISS
GO:0030041	Process	Actin filament polymerization	ISS
GO:0030667	Component	Secretory granule membrane	TAS
GO:0032587	Component	Ruffle membrane	IEA
GO:0032886	Process	Regulation of microtubule-based process	IMP	20937854
GO:0035372	Process	Protein localization to microtubule	IMP	15123714
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0044325	Function	Ion channel binding	IPI	15123714
GO:0051279	Process	Regulation of release of sequestered calcium ion into cytosol	IMP	15123714
GO:0051493	Process	Regulation of cytoskeleton organization	IMP	26912466
GO:0071420	Process	Cellular response to histamine	IMP	15123714
GO:0072686	Component	Mitotic spindle	IDA	15123714
GO:0101003	Component	Ficolin-1-rich granule membrane	TAS
GO:2000145	Process	Regulation of cell motility	TAS

Other IDs

• MIM: 602121
• HGNC: 2876
• e!Ensembl: ENSG00000131504

Protein

• UniProt ID: O60610
• Protein name: Protein diaphanous homolog 1 (Diaphanous-related formin-1) (DRF1)
• Protein function: Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:20937854, PubMed:21834987). Plays a role in brain development (PubMed:24781755). 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 (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06371	Drf_GBD	84 → 268	Diaphanous GTPase-binding Domain	Family
  PF06367	Drf_FH3	274 → 464	Diaphanous FH3 Domain	Family
  PF06346	Drf_FH1	614 → 691		Repeat
  PF06346	Drf_FH1	662 → 764		Repeat
  PF02181	FH2	769 → 1146	Formin Homology 2 Domain	Family
  PF06345	Drf_DAD	1197 → 1211	DRF Autoregulatory Domain	Motif

• Sequence:

  MEPPGGSLGPGRGTRDKKKGRSPDELPSAGGDGGKSKKFTLKRLMADELERFTSMRIKKE
  KEKPNSAHRNSSASYGDDPTAQSLQDVSDEQVLVLFEQMLLDMNLNEEKQQPLREKDIII
  KREMVSQYLYTSKAGMSQKESSKSAMMYIQELRSGLRDMPLLSCLESLRVSLNNNPVSWV
  QTFGAEGLASLLDILKRLHDEKEETAGSYDSRNKHEIIRCLKAFMNNKFGIKTMLETEEG
  ILLLVRAMDPAVPNMMIDAAKLLSALCILPQPEDMNERVLEAMTERAEMDEVERFQPLLD
  GLKSGTTIALKVGCLQLINALITPAEELDFRVHIRSELMRLGLHQVLQDLREIENEDMRV
  QLNVFDEQGEEDSYDLKGRLDDIRMEMDDFNEVFQILLNTVKDSKAEPHFLSILQHLLLV
  RNDYEARPQYYKLIEECISQIVLHKNGADPDFKCRHLQIEIEGLIDQMIDKTKVEKSEAK
  AAELEKKLDSELTARHELQVEMKKMESDFEQKLQDLQGEKDALHSEKQQIATEKQDLEAE
  VSQLTGEVAKLTKELEDAKKEMASLSAAAITVPPSVPSRAPVPPAPPLPGDSGTIIPPPP
  APGDSTTPPPPPPPPPPPPPLPGGVCISSPPSLPGGTAISPPPPLSGDATIPPPPPLPEG
  VGIPSPSSLPGGTAIPPPPPLPGSARIPPPPPPLPGSAGIPPPPPPLPGEAGMPPPPPPL
  PGGPGIPPPPPFPGGPGIPPPPPGMGMPPPPPFGFGVPAAPVLPFGLTPKKLYKPEVQLR
  RPNWSKLVAEDLSQDCFWTKVKEDRFENNELFAKLTLTFSAQTKTSKAKKDQEGGEEKKS
  VQKKKVKELKVLDSKTAQNLSIFLGSFRMPYQEIKNVILEVNEAVLTESMIQNLIKQMPE
  PEQLKMLSELKDEYDDLAESEQFGVVMGTVPRLRPRLNAILFKLQFSEQVENIKPEIVSV
  TAACEELRKSESFSNLLEITLLVGNYMNAGSRNAGAFGFNISFLCKLRDTKSTDQKMTLL
  HFLAELCENDYPDVLKFPDELAHVEKASRVSAENLQKNLDQMKKQISDVERDVQNFPAAT
  DEKDKFVEKMTSFVKDAQEQYNKLRMMHSNMETLYKELGEYFLFDPKKLSVEEFFMDLHN
  FRNMFLQAVKENQKRRETEEKMRRAKLAKEKAEKERLEKQQKREQLIDMNAEGDETGVMD
  SLLEALQSGAAFRRKRGPRQANRKAGCAVTSLLASELTKDDAMAAVPAKVSKNSETFPTI
  LEEAKELVGRAS

• Sequence length: 1272