OTOG

otogelin

Basic information

Region (hg38): 11:17547259-17647150

Links

ENSG00000188162 ∙ NCBI:340990 ∙ OMIM:604487 ∙ HGNC:8516 ∙ Uniprot:Q6ZRI0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 18B (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 18B (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 18B (Moderate), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 18B (Definitive), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 18B	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	23122587

ClinVar

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

• not provided (29 variants)
• Autosomal recessive nonsyndromic hearing loss 18B (13 variants)
• Hearing impairment (1 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTOG 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			7	226	24	257
missense		4	378	42	30	454
nonsense	21	21	1			43
start loss			1			1
frameshift	18	12	2			32
inframe indel			7			7
splice donor/acceptor (+/-2bp)	3	14				17
splice region			13	29	5	47
non coding		1	9	159	138	307
Total	42	52	405	427	192

Highest pathogenic variant AF is 0.0000459

Variants in OTOG

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

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

Position	Type	Phenotype	Significance	ClinVar
11-17547359-CC-GA		not specified	not provided (Jun 16, 2015)
11-17547373-A-G			Uncertain significance (Mar 15, 2019)
11-17547385-G-A			Uncertain significance (Apr 26, 2024)
11-17547386-C-T		not specified	Uncertain significance (Jun 07, 2016)
11-17547387-G-A			Uncertain significance (Jun 06, 2022)
11-17547388-T-C		not specified	Likely benign (Nov 28, 2018)
11-17547393-G-A		not specified	Benign (Dec 25, 2023)
11-17547414-C-T			Likely benign (Nov 13, 2023)
11-17547417-GCTGCC-G			Pathogenic (Dec 14, 2023)
11-17547422-C-T			Uncertain significance (Jun 17, 2023)
11-17547442-G-A			Uncertain significance (Aug 18, 2023)
11-17547448-C-T		not specified	Likely benign (Feb 22, 2018)
11-17547449-T-A		Autosomal recessive nonsyndromic hearing loss 18B	Uncertain significance (May 26, 2020)
11-17547465-C-T			Conflicting classifications of pathogenicity (Aug 30, 2023)
11-17547466-G-A			Uncertain significance (Mar 27, 2017)
11-17547483-C-T			Uncertain significance (Jan 25, 2022)
11-17547502-C-G			Uncertain significance (Jan 27, 2022)
11-17547503-G-A		not specified	Benign (Jan 29, 2024)
11-17547516-C-T			Likely benign (Feb 20, 2023)
11-17547517-G-A			Uncertain significance (Nov 15, 2022)
11-17547520-A-G			Uncertain significance (Feb 03, 2022)
11-17547528-G-A			Uncertain significance (Apr 14, 2022)
11-17547540-C-T			Likely benign (Mar 01, 2024)
11-17547541-G-A			Uncertain significance (Jul 04, 2023)
11-17547541-G-T		not specified • OTOG-related disorder	Conflicting classifications of pathogenicity (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OTOG	protein_coding	protein_coding	ENST00000399391	55	99778

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.61e-37	1.00	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.92	1413	1.63e+3	0.866	0.0000986	18693
Missense in Polyphen		484	572.38	0.84559		6837
Synonymous	2.64	595	683	0.871	0.0000433	6070
Loss of Function	3.96	79	127	0.621	0.00000661	1495

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glycoprotein specific to acellular membranes of the inner ear. May be required for the anchoring of the otoconial membranes and cupulae to the underlying neuroepithelia in the vestibule. May be involved in the organization and/or stabilization of the fibrillar network that compose the tectorial membrane in the cochlea. May play a role in mechanotransduction processes (By similarity). {ECO:0000250}.
• Disease: DISEASE: Deafness, autosomal recessive, 18B (DFNB18B) [MIM:614945]: A form of non-syndromic deafness characterized by a moderate hearing impairment, which can be associated with vestibular dysfunction, and a flat to shallow "U" or slightly downsloping shaped audiograms. {ECO:0000269|PubMed:23122587}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Haploinsufficiency Scores

• pHI: 0.0827
• ghis: 0.407

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.130

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Otog
• Phenotype: hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype

Zebrafish Information Network

• Gene name: otog
• Affected structure: otolith
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: sensory perception of sound;adult locomotory behavior;L-arabinose metabolic process
• Cellular component: extracellular space;apical plasma membrane
• Molecular function: structural molecule activity;alpha-L-arabinofuranosidase activity