OTOS

Summary

OTOS (otospiralin, HGNC:22644) is a protein-coding gene on chromosome 2q37.3, encoding Otospiralin (Q8NHW6). May be essential for the survival of the neurosensory epithelium of the inner ear.

Otospiralin is synthesized by nonsensory cells (fibrocytes) of the inner ear, and downregulation of otospiralin in guinea pigs leads to deafness (Lavigne-Rebillard et al., 2003 [PubMed 12687421]).

Source: NCBI Gene 150677 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 22 total — 1 pathogenic
• MANE Select transcript: NM_148961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22644
Approved symbol	OTOS
Name	otospiralin
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	OTOSP
Ensembl gene	ENSG00000178602
Ensembl biotype	protein_coding
OMIM	607877
Entrez	150677

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000319460, ENST00000391989, ENST00000908574

RefSeq mRNA: 1 — MANE Select: NM_148961 NM_148961

CCDS: CCDS2533

Canonical transcript exons

ENST00000319460 — 4 exons

Exon	Start	End
ENSE00001259793	240140062	240140088
ENSE00001292779	240140269	240140444
ENSE00001317177	240140620	240140658
ENSE00003742443	240139026	240139354

Expression profiles

Bgee: expression breadth broad, 73 present calls, max score 93.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2398 / max 73.5620, expressed in 47 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34822	0.1393	34
34821	0.0583	10
34820	0.0237	8
34823	0.0184	4

Top tissues by expression

218 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	93.45	gold quality
adenohypophysis	UBERON:0002196	91.94	gold quality
left lobe of thyroid gland	UBERON:0001120	88.55	gold quality
thyroid gland	UBERON:0002046	87.92	gold quality
right lobe of thyroid gland	UBERON:0001119	84.99	gold quality
amygdala	UBERON:0001876	75.56	gold quality
putamen	UBERON:0001874	73.56	gold quality
caudate nucleus	UBERON:0001873	71.06	gold quality
anterior cingulate cortex	UBERON:0009835	70.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.72	gold quality
right frontal lobe	UBERON:0002810	66.98	gold quality
forebrain	UBERON:0001890	65.36	gold quality
temporal lobe	UBERON:0001871	64.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.42	gold quality
hypothalamus	UBERON:0001898	63.82	gold quality
Ammon’s horn	UBERON:0001954	63.58	gold quality
brain	UBERON:0000955	62.79	gold quality
caput epididymis	UBERON:0004358	62.60	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	62.45	gold quality
neocortex	UBERON:0001950	61.68	gold quality
nucleus accumbens	UBERON:0001882	61.58	gold quality
cerebral cortex	UBERON:0000956	61.47	gold quality
prefrontal cortex	UBERON:0000451	61.41	gold quality
spinal cord	UBERON:0002240	60.43	gold quality
frontal cortex	UBERON:0001870	60.26	gold quality
ventricular zone	UBERON:0003053	59.78	gold quality
primary visual cortex	UBERON:0002436	57.87	gold quality
substantia nigra	UBERON:0002038	57.65	gold quality
midbrain	UBERON:0001891	55.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	54.20	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting OTOS, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-663A	94.99	63.54	378

Literature-anchored findings (GeneRIF, showing 2)

• OTOSP spans 1630 nucleotides, has 4 exons & encodes a 567-base cDNA. OTOSP is on chromosome 2 at position q37.3. Beside intronic polymorphisms, a rare variant (Pro7Leu) was found in deafness patients & controls, excluding it as a genetic deafness gene. (PMID:12687421)
• study indicates a potentially protective role for the variant G alleles of SNPs rs77124181 and rs2291767 in Otos against the development of cisplatin-induced ototoxicity (PMID:25410892)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	otos	ENSDARG00000108475
mus_musculus	Otos	ENSMUSG00000044055
rattus_norvegicus	Otos	ENSRNOG00000016567

Protein

Protein identifiers

Otospiralin — Q8NHW6 (reviewed: Q8NHW6)

All UniProt accessions (1): Q8NHW6

UniProt curated annotations — full annotation on UniProt →

Function. May be essential for the survival of the neurosensory epithelium of the inner ear.

Subcellular location. Secreted.

Tissue specificity. Ear specific.

Similarity. Belongs to the otospiralin family.

RefSeq proteins (1): NP_683764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028224	Otospiralin	Family

Pfam: PF15182

UniProt features (3 total): signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHW6-F1	81.86	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 50 (showing top): GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, WTGAAAT_UNKNOWN, GOBP_SENSORY_PERCEPTION, E2A_Q2, MARTENS_TRETINOIN_RESPONSE_UP, FOXJ2_TARGET_GENES, ZNF26_TARGET_GENES, GSE11924_TH1_VS_TH17_CD4_TCELL_UP, GSE14308_TH2_VS_TH17_UP, GSE14308_TH2_VS_NATURAL_TREG_UP, GSE14308_TH1_VS_TH17_UP, GSE14308_TH1_VS_NAIVE_CD4_TCELL_UP, GSE14308_TH1_VS_INDUCED_TREG_UP, GSE14308_TH1_VS_NATURAL_TREG_UP, chr2q37

GO Biological Process (1): sensory perception of sound (GO:0007605)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory perception of mechanical stimulus	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OTOS	CDH23	Q9H251	618
OTOS	TECTA	O75443	592
OTOS	OTOR	Q9NRC9	541
OTOS	OTOA	Q7RTW8	527
OTOS	TECTB	Q96PL2	500
OTOS	COCH	O43405	479
OTOS	SAMD7	Q7Z3H4	471
OTOS	GPR160	Q9UJ42	469
OTOS	ENSA	O43768	445
OTOS	OTOG	Q6ZRI0	442
OTOS	COPS9	Q8WXC6	438
OTOS	SYMPK	Q92797	432
OTOS	SEC62	Q99442	421
OTOS	OC90	Q02509	397
OTOS	TWF2	Q6IBS0	372

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CCDC125	OTOS	psi-mi:“MI:0915”(physical association)	0.560
VAC14	OTOS	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	OTOS	psi-mi:“MI:0915”(physical association)	0.560
OTOS	CCDC125	psi-mi:“MI:0915”(physical association)	0.000
OTOS	VAC14	psi-mi:“MI:0915”(physical association)	0.000
OTOS	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): OTOS (Two-hybrid), CCDC125 (Two-hybrid), CYSRT1 (Two-hybrid), RAB2A (Two-hybrid), GNMT (Two-hybrid), NGB (Two-hybrid), ATG13 (Two-hybrid)

ESM2 similar proteins: A0JMK6, A5A6J6, B7TB45, B9WZ56, D4A540, P01165, P01172, P01282, P01364, P05408, P0CAX4, P0CD95, P0DJK1, P10124, P10683, P12285, P12961, P13609, P16043, P17322, P18844, P20616, P22334, P27682, P39035, P40147, P47212, P47932, P48144, P51456, Q0P5P2, Q1RMJ9, Q23262, Q32KM8, Q566V9, Q5FVX5, Q5NRQ1, Q7ZXZ6, Q80XD8, Q810H5

Diamond homologs: Q8K559, Q8K560, Q8NHW6, Q8R448

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625781	GRCh37/hg19 2q37.3(chr2:239071623-243048760)	Pathogenic

SpliceAI

766 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240139355:C:CC	acceptor_gain	0.9900
2:240140059:TAC:T	donor_loss	0.9900
2:240140060:ACC:A	donor_loss	0.9900
2:240140061:C:A	donor_loss	0.9900
2:240140063:T:TA	donor_gain	0.9900
2:240140085:GCCCC:G	acceptor_loss	0.9900
2:240140089:C:CG	acceptor_loss	0.9900
2:240140090:T:G	acceptor_loss	0.9900
2:240139352:GGT:G	acceptor_gain	0.9800
2:240139352:GGTCT:G	acceptor_loss	0.9800
2:240139354:TCTG:T	acceptor_loss	0.9800
2:240139355:CT:C	acceptor_loss	0.9800
2:240139356:T:G	acceptor_loss	0.9800
2:240140067:T:TA	donor_gain	0.9800
2:240140086:CCC:C	acceptor_gain	0.9800
2:240140087:CC:C	acceptor_gain	0.9800
2:240140087:CCC:C	acceptor_gain	0.9800
2:240140088:CC:C	acceptor_gain	0.9800
2:240140089:C:CC	acceptor_gain	0.9800
2:240140614:GCTTA:G	donor_loss	0.9800
2:240140615:CTTA:C	donor_loss	0.9800
2:240140616:TTA:T	donor_loss	0.9800
2:240140617:TACCT:T	donor_loss	0.9800
2:240140619:C:CA	donor_loss	0.9800
2:240144522:ACC:A	donor_gain	0.9800
2:240144523:CCC:C	donor_gain	0.9800
2:240139351:GGGT:G	acceptor_gain	0.9700
2:240140017:CCAG:C	donor_gain	0.9700
2:240140028:T:C	donor_gain	0.9700
2:240140060:ACCT:A	donor_gain	0.9700

AlphaMissense

576 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240139300:A:G	F47S	0.988
2:240139320:C:A	W40C	0.985
2:240139320:C:G	W40C	0.985
2:240139299:G:C	F47L	0.981
2:240139299:G:T	F47L	0.981
2:240139301:A:G	F47L	0.981
2:240139227:A:C	F71L	0.970
2:240139227:A:T	F71L	0.970
2:240139229:A:G	F71L	0.970
2:240139300:A:C	F47C	0.968
2:240139322:A:G	W40R	0.965
2:240139322:A:T	W40R	0.965
2:240139240:G:T	A67D	0.962
2:240139237:C:G	R68P	0.955
2:240139296:C:A	W48C	0.954
2:240139296:C:G	W48C	0.954
2:240139231:A:G	F70S	0.953
2:240139229:A:T	F71I	0.947
2:240139228:A:C	F71C	0.943
2:240139228:A:G	F71S	0.941
2:240139298:A:G	W48R	0.941
2:240139298:A:T	W48R	0.941
2:240139241:C:G	A67P	0.934
2:240139268:C:A	G58W	0.933
2:240139314:G:C	F42L	0.933
2:240139314:G:T	F42L	0.933
2:240139316:A:G	F42L	0.933
2:240139267:C:A	G58V	0.920
2:240139303:T:A	D46V	0.918
2:240139229:A:C	F71V	0.917

dbSNP variants (sampled 300 via entrez): RS1000150714 (2:240142441 G>A), RS1000371609 (2:240142619 G>A), RS1001103995 (2:240139899 A>G), RS1001200055 (2:240141212 G>T), RS1003030050 (2:240142548 G>A), RS1003204291 (2:240139041 C>T), RS1003562595 (2:240141082 C>G), RS1004203425 (2:240140606 T>A), RS1007930727 (2:240140638 G>A), RS1008541991 (2:240140466 T>A), RS1009465910 (2:240139771 C>T), RS1009612384 (2:240139635 G>T), RS1009947116 (2:240138652 C>T), RS1010042149 (2:240141165 G>A), RS1011081658 (2:240139832 C>T)

Disease associations

OMIM: gene MIM:607877 | disease phenotypes: MIM:600430

GenCC curated gene-disease

Mondo (1): 2q37 microdeletion syndrome (MONDO:0010886)

Orphanet (1): 2q37 microdeletion syndrome (Orphanet:1001)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003855_18	Gut microbiota (bacterial taxa)	4.000000e-08
GCST007796_8	Tinnitus in cisplatin-treated testicular cancer	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538317	Chromosome 2q37 deletion syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2291767	Toxicity	3	cisplatin	Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2291767	OTOS	3	0.00	1	cisplatin

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects response to substance, decreases response to substance	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Lead	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight