OTOL1

protein-coding

otolin 1, the group of C1q and TNF related

Gene summary

This gene encodes a secreted glycoprotein with a C-terminal complement Cq1-like globular domain that belongs to the C1q/tumor necrosis factor-related protein (CTRP) family. The encoded protein is expressed in the inner ear and forms a multimeric complex called the otoconia, together with cerebellin-1 and otoconin-90, as part of the otoconial membrane. It contains extensive posttranslational modifications including hydroxylated prolines and glycosylated lysines. Naturally occurring mutations in this gene are associated with abnormal otoconia formation and balance deficits resulting from vestibular dysfunction. [provided by RefSeq, Jul 2017]

MANE transcript

NM_001080440.1

Inheritance

—

ClinVar variants

U:62B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.3

Max pathogenic AF

—

Genomic locus

chr3:161,496,808-161,503,942

External References & Databases

Ensembl (ENSG00000182447)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OTOL1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 67

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080440.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			62 clinvar	5 clinvar		67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	5	0	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080440.1	RefSeq	NP_001073909.1	4	MANE Select
ENST00000327928.4	Ensembl	ENSP00000330808.4	4	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

extracellular matrix organization
otolith mineralization
protein homooligomerization

Molecular Function

extracellular matrix structural constituent
calcium ion binding

Cellular Component

extracellular region
collagen trimer
extracellular space
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327928
Coding exons: 4
Length: 7135
Individuals with no LoFs: 124536
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 124628
p: 0.000369

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.967	270	229	1.18	0.0000114	3042
Missense (PolyPhen)		77	69.35	1.1103		847
Synonymous	-0.0368	85	84.6	1.01	0.00000441	970
Loss of Function	-1.09	20	15.4	1.30	8.81e-7	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0017	0.0017	notable
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00031	0.00030	rare
South Asian	0.00023	0.00023	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Collagen-like protein specifically expressed in the inner ear, which provides an organic scaffold for otoconia, a calcium carbonate structure in the saccule and utricle of the ear. Acts as a scaffold for biomineralization: sequesters calcium and forms interconnecting fibrils between otoconia that are incorporated into the calcium crystal structure. Together with OC90, modulates calcite crystal morphology and growth kinetics. {ECO:0000250|UniProtKB:Q4ZJM7}.;

Intolerance Scores

LoFtool: 0.456
RVIS EVS: 0.06
RVIS percentile EVS: 58.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.200

Gene Damage Prediction

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