OTOL1

Chr 3

otolin 1

Also known as: C1QTNF15, C1QTNF16

NCBI Gene: 131149 ENSG00000182447 UniProt: A6NHN0 OMIM: 621480

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.81

Clinical Summary— OTOL1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

62 VUS of 67 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.000

Z-score -1.09

OE 1.30 (0.91–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.97Z-score

OE missense 1.18 (1.07–1.30)

270 obs / 228.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.30 (0.91–1.81)

0≤0.351.4

Missense OE?1.18 (1.07–1.30)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 20 / 15.4Missense obs/exp: 270 / 228.9Syn Z: -0.04

This gene — mechanism propensity

0.75top 25%

GOF

0.5367th %ile

LOF

0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

VUS62

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	62	62
Likely Benign	5	5
Benign	0	0
Total	67	67

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

20 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap OTOL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →