DIABLO

diablo IAP-binding mitochondrial protein

Basic information

Region (hg38): 12:122207668-122226062

Links

ENSG00000184047 ∙ NCBI:56616 ∙ OMIM:605219 ∙ HGNC:21528 ∙ Uniprot:Q9NR28 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 64 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 64 (Limited), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 64	AD	General	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	21722859

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DIABLO gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	1	12
missense			33	5	1	39
nonsense						0
start loss						0
frameshift			4			4
inframe indel				1		1
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1		2
non coding			2	24	19	45
Total	0	0	40	41	21

Variants in DIABLO

This is a list of pathogenic ClinVar variants found in the DIABLO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-122208118-T-TA			Benign (Dec 10, 2018)
12-122208273-T-C			Benign (Jun 22, 2018)
12-122208303-C-T			Likely benign (Jun 13, 2021)
12-122208327-A-G			Benign (Jun 16, 2018)
12-122208383-A-G		Autosomal dominant nonsyndromic hearing loss 64	Likely pathogenic (May 06, 2024)
12-122208388-TCACGCAGGTAG-T		Hearing impairment	Uncertain significance (Feb 04, 2022)
12-122208391-C-G		not specified	Uncertain significance (Jan 30, 2024)
12-122208391-C-T			Uncertain significance (Nov 21, 2022)
12-122208392-G-A			Uncertain significance (Mar 01, 2023)
12-122208400-GCCTCCTGCTCCGACTCAGCCCGCT-G		DIABLO-related disorder	Likely benign (Dec 17, 2020)
12-122208401-CC-AG			Uncertain significance (Feb 04, 2022)
12-122208411-C-T		not specified	Benign (Jan 29, 2024)
12-122208412-G-A			Uncertain significance (Jan 11, 2024)
12-122208426-C-T			Likely benign (Jul 11, 2022)
12-122208431-C-T		not specified • DIABLO-related disorder	Benign/Likely benign (Jan 07, 2024)
12-122208441-T-C		not specified	Likely benign (Jan 16, 2018)
12-122208465-CTG-C		not specified	Uncertain significance (May 21, 2019)
12-122208474-T-C			Likely benign (Oct 22, 2022)
12-122208487-T-G			Uncertain significance (Jul 17, 2022)
12-122208490-G-A			Uncertain significance (Dec 25, 2023)
12-122208496-C-T		Autosomal dominant nonsyndromic hearing loss 64	Conflicting classifications of pathogenicity (Apr 11, 2023)
12-122208497-G-A		DIABLO-related disorder	Uncertain significance (May 03, 2023)
12-122208508-T-C			Uncertain significance (Dec 06, 2022)
12-122208534-C-T			Likely benign (Nov 14, 2022)
12-122208555-G-A		not specified	Benign/Likely benign (Nov 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DIABLO	protein_coding	protein_coding	ENST00000443649	6	19872

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000257	0.522	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.12	161	126	1.28	0.00000711	1529
Missense in Polyphen		57	48.708	1.1702		614
Synonymous	-2.22	65	45.9	1.42	0.00000239	467
Loss of Function	0.764	10	13.0	0.771	6.46e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.000192	0.000185
European (Non-Finnish)	0.000172	0.000167
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000181	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis- inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance. {ECO:0000269|PubMed:10929711, ECO:0000269|PubMed:14523016, ECO:0000269|PubMed:15200957}.
• Disease: DISEASE: Deafness, autosomal dominant, 64 (DFNA64) [MIM:614152]: 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. {ECO:0000269|PubMed:21722859}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Apoptosis - multiple species - Homo sapiens (human);Apoptosis - Homo sapiens (human);Apoptosis Modulation and Signaling;TNF alpha Signaling Pathway;Nanomaterial induced apoptosis;Apoptosis;Apoptotic Signaling Pathway;role of mitochondria in apoptotic signaling;Release of apoptotic factors from the mitochondria;SMAC-mediated dissociation of IAP:caspase complexes ;SMAC-mediated apoptotic response;Apoptotic factor-mediated response;Intrinsic Pathway for Apoptosis;Apoptosis;Programmed Cell Death;SMAC binds to IAPs ;TNFalpha;Caspase Cascade in Apoptosis;p75(NTR)-mediated signaling (Consensus)

Intolerance Scores

• loftool: 0.603
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.0999
• hipred: Y
• hipred_score: 0.562
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Diablo
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;extrinsic apoptotic signaling pathway via death domain receptors;intrinsic apoptotic signaling pathway in response to oxidative stress;activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c;positive regulation of apoptotic process;neuron apoptotic process;intrinsic apoptotic signaling pathway
• Cellular component: mitochondrion;mitochondrial intermembrane space;cytosol;cytoplasmic side of plasma membrane;CD40 receptor complex
• Molecular function: protein binding