DIAPH3

diaphanous related formin 3, the group of Formins|Armadillo like helical domain containing

Basic information

Region (hg38): 13:59665583-60163928

Previous symbols: [ "AUNA1" ]

Links

ENSG00000139734 ∙ NCBI:81624 ∙ OMIM:614567 ∙ HGNC:15480 ∙ Uniprot:Q9NSV4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant auditory neuropathy 1 (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant auditory neuropathy 1 (Limited), mode of inheritance: Unknown
• auditory neuropathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Auditory neuropathy, autosomal dominant, 1	AD	Audiologic/Otolaryngologic	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	20624953

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DIAPH3 gene.

• not_provided (378 variants)
• not_specified (168 variants)
• DIAPH3-related_disorder (27 variants)
• Autosomal_dominant_auditory_neuropathy_1 (20 variants)
• Hearing_impairment (5 variants)
• Auditory_neuropathy (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DIAPH3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001042517.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	72	5	78
missense			266	28	6	300
nonsense			8			8
start loss						0
frameshift	1		15			16
splice donor/acceptor (+/-2bp)			12			12
Total	1	0	302	100	11

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DIAPH3	protein_coding	protein_coding	ENST00000400324	28	498405

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124538	0	256	124794	0.00103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.257	605	623	0.971	0.0000315	7902
Missense in Polyphen		248	274	0.90511		3557
Synonymous	-0.857	241	225	1.07	0.0000116	2143
Loss of Function	3.20	34	61.0	0.558	0.00000296	823

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00211	0.00211
Ashkenazi Jewish	0.00	0.00
East Asian	0.000952	0.000946
Finnish	0.000372	0.000371
European (Non-Finnish)	0.00119	0.00117
Middle Eastern	0.000952	0.000946
South Asian	0.00105	0.00105
Other	0.00116	0.00115

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000250|UniProtKB:Q9Z207}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:20624953}. Note=The disease is caused by mutations affecting the gene represented in this entry. A disease- causing mutation in the conserved 5'-UTR leads to increased protein expression. {ECO:0000269|PubMed:20624953}.
• Pathway: Regulation of actin cytoskeleton - Homo sapiens (human);Regulation of Actin Cytoskeleton;Signal Transduction;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;ErbB1 downstream signaling;CDC42 signaling events (Consensus)

Recessive Scores

• pRec: 0.0850

Intolerance Scores

• loftool: 0.230
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.27

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.710

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: cytoskeleton organization;spermatogenesis;actin cytoskeleton organization;actin filament polymerization
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: actin binding;Rho GTPase binding;cadherin binding