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 (1157 variants)
not_specified (260 variants)
OTOG-related_disorder (118 variants)
Autosomal_recessive_nonsyndromic_hearing_loss_18B (109 variants)
Rare_genetic_deafness (22 variants)
Meniere_disease (12 variants)
Hearing_impairment (7 variants)
Hearing_loss,_autosomal_recessive (3 variants)
Autosomal_recessive_disease (2 variants)
Deafness (1 variants)
Intellectual_disability (1 variants)
Nonsyndromic_genetic_hearing_loss (1 variants)
Hearing_loss (1 variants)
Seizure (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. These statistics are base on transcript: NM_001292063.2. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			10 clinvar	271 clinvar	19 clinvar	300
missense	1 clinvar	7 clinvar	488 clinvar	90 clinvar	13 clinvar	599
nonsense	29 clinvar	28 clinvar	1 clinvar			58
start loss			1			1
frameshift	19 clinvar	19 clinvar	4 clinvar			42
splice donor/acceptor (+/-2bp)	4 clinvar	21 clinvar	1 clinvar			26
Total	53	75	505	361	32

Highest pathogenic variant AF is 0.0004048042

Loading clinvar variants...

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
hipred
hipred_score
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