OTOP1

otopetrin 1

Basic information

Region (hg38): 4:4188726-4226929

Links

ENSG00000163982 ∙ NCBI:133060 ∙ OMIM:607806 ∙ HGNC:19656 ∙ Uniprot:Q7RTM1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OTOP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTOP1 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						0
missense			47	3		50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	47	3	0

Variants in OTOP1

This is a list of pathogenic ClinVar variants found in the OTOP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-4188841-C-T		not specified	Uncertain significance (Jan 12, 2024)
4-4188898-G-T		not specified	Uncertain significance (Oct 29, 2024)
4-4188919-C-T		not specified	Uncertain significance (Jul 09, 2024)
4-4188928-C-T		not specified	Uncertain significance (Jan 23, 2024)
4-4188968-C-G		not specified	Uncertain significance (Mar 25, 2022)
4-4197184-C-A		not specified	Uncertain significance (Mar 11, 2024)
4-4197192-C-A		not specified	Uncertain significance (May 24, 2023)
4-4197213-T-C		not specified	Uncertain significance (Jun 19, 2024)
4-4197230-T-A		not specified	Uncertain significance (Dec 27, 2023)
4-4197239-C-T		not specified	Uncertain significance (Jun 29, 2022)
4-4197240-G-A		not specified	Uncertain significance (Oct 26, 2022)
4-4197242-G-A		not specified	Uncertain significance (Apr 07, 2023)
4-4197282-C-T		not specified	Uncertain significance (Dec 03, 2024)
4-4197335-T-C		not specified	Uncertain significance (Jun 24, 2022)
4-4197395-T-C		not specified	Uncertain significance (Aug 02, 2022)
4-4197411-C-A		not specified	Uncertain significance (Jul 17, 2024)
4-4197416-G-C		not specified	Uncertain significance (May 30, 2024)
4-4197473-A-T		not specified	Uncertain significance (Dec 18, 2023)
4-4197474-G-T		not specified	Uncertain significance (Dec 18, 2023)
4-4197539-G-C		not specified	Uncertain significance (Jan 04, 2024)
4-4197539-G-T		not specified	Uncertain significance (Jul 20, 2021)
4-4197575-C-A		not specified	Uncertain significance (Aug 01, 2024)
4-4197576-G-A		not specified	Uncertain significance (Feb 15, 2023)
4-4197593-C-G		not specified	Uncertain significance (Jul 09, 2021)
4-4197614-C-T		not specified	Uncertain significance (Nov 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OTOP1	protein_coding	protein_coding	ENST00000296358	6	38087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.84e-24	0.0000125	125515	0	233	125748	0.000927

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.664	356	322	1.10	0.0000179	3874
Missense in Polyphen		117	106.19	1.1018		1369
Synonymous	-0.312	141	136	1.03	0.00000804	1267
Loss of Function	-1.95	30	20.5	1.47	0.00000103	244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00124	0.00124
Ashkenazi Jewish	0.00	0.00
East Asian	0.000436	0.000435
Finnish	0.000554	0.000554
European (Non-Finnish)	0.00130	0.00129
Middle Eastern	0.000436	0.000435
South Asian	0.000915	0.000915
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Proton-selective channel that specifically transports protons into cells (PubMed:29371428). Proton channel activity is only weakly-sensitive to voltage (By similarity). Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes (PubMed:29371428). In the vestibular system of the inner ear, required for the formation and function of otoconia, which are calcium carbonate crystals that sense gravity and acceleration (By similarity). Probably acts by maintaining the pH appropriate for formation of otoconia (By similarity). Regulates purinergic control of intracellular calcium in vestibular supporting cells (By similarity). May be involved in sour taste perception in sour taste cells by mediating entry of protons within the cytosol (By similarity). Also involved in energy metabolism, by reducing adipose tissue inflammation and protecting from obesity-induced metabolic dysfunction (By similarity). {ECO:0000250|UniProtKB:Q80VM9, ECO:0000269|PubMed:29371428}.

Intolerance Scores

• loftool: 0.927
• rvis_EVS: 0.42
• rvis_percentile_EVS: 77.26

Haploinsufficiency Scores

• pHI: 0.0944
• hipred: N
• hipred_score: 0.264

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.209

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Otop1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: otop1
• Affected structure: otolith
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: detection of gravity;biomineral tissue development;cellular response to insulin stimulus;inner ear morphogenesis;negative regulation of interferon-gamma-mediated signaling pathway;proton transmembrane transport
• Cellular component: integral component of plasma membrane
• Molecular function: proton channel activity