OC90

Summary

OC90 (otoconin 90, HGNC:8100) is a protein-coding gene on chromosome 8q24.22, encoding Otoconin-90 (Q02509). Major protein of the otoconia, a calcium carbonate structure in the saccule and utricle of the ear.

Predicted to enable calcium ion binding activity; calcium-dependent phospholipase A2 activity; and phospholipid binding activity. Predicted to be involved in otolith mineralization; phosphatidylcholine metabolic process; and phosphatidylglycerol metabolic process. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix.

Source: NCBI Gene 729330 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001080399

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8100
Approved symbol	OC90
Name	otoconin 90
Location	8q24.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000253117
Ensembl biotype	protein_coding
OMIM	601658
Entrez	729330

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000254627

RefSeq mRNA: 1 — MANE Select: NM_001080399 NM_001080399

CCDS: CCDS47919

Canonical transcript exons

ENST00000254627 — 14 exons

Exon	Start	End
ENSE00003465606	132031881	132032052
ENSE00003480482	132044433	132044489
ENSE00003481231	132054981	132055073
ENSE00003524532	132041044	132041156
ENSE00003533786	132034781	132034834
ENSE00003539699	132038995	132039123
ENSE00003559058	132045818	132045883
ENSE00003564183	132029073	132029179
ENSE00003575996	132038790	132038831
ENSE00003621606	132037438	132037488
ENSE00003624858	132041525	132041699
ENSE00003637369	132024216	132024776
ENSE00003649085	132059341	132059382
ENSE00003663803	132033039	132033164

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 89.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0301 / max 12.6432, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95046	0.0301	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.49	gold quality
cortical plate	UBERON:0005343	44.35	silver quality
ganglionic eminence	UBERON:0004023	42.55	silver quality
substantia nigra	UBERON:0002038	42.13	gold quality
colonic epithelium	UBERON:0000397	41.07	gold quality
bone marrow cell	CL:0002092	40.64	gold quality
placenta	UBERON:0001987	40.03	gold quality
prefrontal cortex	UBERON:0000451	38.20	silver quality
sural nerve	UBERON:0015488	36.76	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
frontal cortex	UBERON:0001870	35.70	silver quality
hypothalamus	UBERON:0001898	34.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	34.28	silver quality
Brodmann (1909) area 9	UBERON:0013540	34.28	silver quality
bone marrow	UBERON:0002371	34.03	gold quality
cerebral cortex	UBERON:0000956	33.97	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
anterior cingulate cortex	UBERON:0009835	32.41	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
brain	UBERON:0000955	30.61	gold quality
primary visual cortex	UBERON:0002436	30.35	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
superior frontal gyrus	UBERON:0002661	29.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	28.86	gold quality
liver	UBERON:0002107	28.29	gold quality
duodenum	UBERON:0002114	28.14	gold quality
islet of Langerhans	UBERON:0000006	27.97	gold quality
lymph node	UBERON:0000029	27.57	gold quality
leukocyte	CL:0000738	27.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting OC90, 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-4682	100.00	68.89	1258
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-496	98.66	69.80	931

Literature-anchored findings (GeneRIF, showing 2)

• calcium carbonate crystal growth data demonstrate that Otolin-1 and OC90 modulate in vitro calcite crystal morphology but neither protein is sufficient to produce the shape of otoconia (PMID:24748133)
• Serum Otoconin-90 and Otolin-1 Concentrations in Benign Paroxysmal Positional Vertigo. (PMID:39456211)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	oc90	ENSDARG00000001721
mus_musculus	Oc90	ENSMUSG00000015001
rattus_norvegicus	Oc90	ENSRNOG00000025516
caenorhabditis_elegans		WBGENE00007419
caenorhabditis_elegans		WBGENE00015406

Paralogs (8): PLA2G10 (ENSG00000069764), PLA2G2D (ENSG00000117215), PLA2G5 (ENSG00000127472), PLA2G2F (ENSG00000158786), PLA2G1B (ENSG00000170890), PLA2G2C (ENSG00000187980), PLA2G2A (ENSG00000188257), PLA2G2E (ENSG00000188784)

Protein

Protein identifiers

Otoconin-90 — Q02509 (reviewed: Q02509)

Alternative names: Phospholipase A2 homolog

All UniProt accessions (1): Q02509

UniProt curated annotations — full annotation on UniProt →

Function. Major protein of the otoconia, a calcium carbonate structure in the saccule and utricle of the ear. Together with OTOL1, acts as a scaffold for otoconia biomineralization: sequesters calcium and forms interconnecting fibrils between otoconia that are incorporated into the calcium crystal structure. Together with OTOL1, modulates calcite crystal morphology and growth kinetics. It is unlikely that this protein has phospholipase A2 activity.

Subunit / interactions. Interacts with OTOL1.

Subcellular location. Secreted.

Domain organisation. Consists of 3 PA2-type domains.

Similarity. Belongs to the phospholipase A2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q02509-1	1	yes
Q02509-3	2

RefSeq proteins (1): NP_001073868* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001211	PLA2	Family
IPR016090	PLA2-like_dom	Domain
IPR033112	PLA2_Asp_AS	Active_site
IPR033113	PLA2_histidine	Active_site
IPR036444	PLipase_A2_dom_sf	Homologous_superfamily
IPR041798	Otoconin-90	Domain

Pfam: PF00068

UniProt features (22 total): disulfide bond 7, sequence conflict 4, region of interest 4, glycosylation site 3, signal peptide 1, chain 1, splice variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02509-F1	66.43	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (7): 85–145, 99–190, 101–117, 116–172, 123–165, 132–158, 152–163

Glycosylation sites (3): 38, 179, 407

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_EAR_DEVELOPMENT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SECRETION, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_LIPID_CATABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_TRANSPORT

GO Biological Process (6): lipid catabolic process (GO:0016042), otolith mineralization (GO:0045299), phosphatidylcholine metabolic process (GO:0046470), phosphatidylglycerol metabolic process (GO:0046471), arachidonate secretion (GO:0050482), phospholipid metabolic process (GO:0006644)

GO Molecular Function (6): structural molecule activity (GO:0005198), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), A2-type glycerophospholipase activity (GO:0004623), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
glycerophospholipid metabolic process	2
catabolic process	1
biomineral tissue development	1
otolith development	1
icosanoid secretion	1
arachidonate transport	1
organophosphate metabolic process	1
molecular_function	1
metal ion binding	1
lipid binding	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
cation binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OC90	HHLA1	C9JL84	970
OC90	OTOP1	Q7RTM1	904
OC90	OTOL1	A6NHN0	819
OC90	ATP2B2	Q01814	789
OC90	NOX3	Q9HBY0	784
OC90	ATP2B4	P23634	697
OC90	SLC26A4	O43511	683
OC90	CBLN1	P02682	678
OC90	OTOP3	Q7RTS5	604
OC90	OTOP2	Q7RTS6	599
OC90	OTOG	Q6ZRI0	587
OC90	SPP1	P10451	497
OC90	AFDN	P55196	497
OC90	TECTA	O75443	495
OC90	H7C0V5	H7C0V5	490

IntAct

2 interactions, top by confidence:

A	B	Type	Score
OC90	ZNF324	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): ZNF324 (Affinity Capture-MS), BRIP1 (Affinity Capture-MS), GMCL1 (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), ZNF77 (Affinity Capture-MS), NPRL3 (Affinity Capture-MS), STIL (Affinity Capture-MS), ZNF101 (Affinity Capture-MS), RAB3GAP1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), TTF2 (Affinity Capture-MS), GNPTAB (Affinity Capture-MS), MOCOS (Affinity Capture-MS), C5orf34 (Affinity Capture-MS), TRIM65 (Affinity Capture-MS)

ESM2 similar proteins: A6NCL2, D3ZTT2, O19131, O46655, O70280, P01177, P01178, P01179, P01180, P01183, P01185, P01186, P03973, P13389, P19438, P22298, P22934, P25118, P35454, P35455, P50555, P58658, P58659, Q02509, Q14AE4, Q32LD3, Q3URS3, Q5T700, Q68US5, Q6UWE3, Q6UWL2, Q6V9X0, Q6WN34, Q76LW6, Q86Y78, Q8BPP5, Q8BVP6, Q8N6Q3, Q8VEA6, Q8WXA2

Diamond homologs: P81869, Q02509, Q9Z0L3, A8CG90, C0HLF0, C0HM79, F8J2D0, F8J2D2, O15496, O42188, P00593, P00597, P00598, P00600, P00607, P00611, P00612, P00613, P00614, P00615, P00622, P00627, P04054, P04055, P04056, P04057, P04417, P06596, P08872, P08873, P0CG57, P0DJN7, P0DKU1, P0DMT3, P0DTS8, P10116, P10117, P14423, P14556, P19000

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2251 predictions. Top by Δscore:

Variant	Effect	Δscore
8:132024774:CACCT:C	acceptor_gain	1.0000
8:132032049:CAGG:C	acceptor_gain	1.0000
8:132033033:GCTCA:G	donor_loss	1.0000
8:132033034:CTCA:C	donor_loss	1.0000
8:132033035:TCA:T	donor_loss	1.0000
8:132033036:CACCT:C	donor_loss	1.0000
8:132033038:C:CT	donor_loss	1.0000
8:132034843:C:T	acceptor_gain	1.0000
8:132039122:CT:C	acceptor_gain	1.0000
8:132039124:C:CC	acceptor_gain	1.0000
8:132041038:GCTT:G	donor_loss	1.0000
8:132041039:CTTA:C	donor_loss	1.0000
8:132041040:TTACC:T	donor_loss	1.0000
8:132041042:A:AC	donor_gain	1.0000
8:132041042:ACC:A	donor_loss	1.0000
8:132041043:C:CC	donor_gain	1.0000
8:132041043:CCA:C	donor_gain	1.0000
8:132041043:CCAC:C	donor_loss	1.0000
8:132041152:AGCAG:A	acceptor_gain	1.0000
8:132041153:GCAG:G	acceptor_gain	1.0000
8:132041154:CAG:C	acceptor_gain	1.0000
8:132041154:CAGC:C	acceptor_gain	1.0000
8:132041169:C:CT	acceptor_gain	1.0000
8:132045816:A:AC	donor_gain	1.0000
8:132045817:C:CC	donor_gain	1.0000
8:132024774:CACC:C	acceptor_loss	0.9900
8:132024776:CC:C	acceptor_loss	0.9900
8:132024776:CCT:C	acceptor_gain	0.9900
8:132024777:CTTAG:C	acceptor_loss	0.9900
8:132024778:T:C	acceptor_gain	0.9900

AlphaMissense

3135 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:132041674:C:A	W65C	0.996
8:132041674:C:G	W65C	0.996
8:132041676:A:G	W65R	0.992
8:132041676:A:T	W65R	0.992
8:132031944:A:C	F323C	0.989
8:132041633:A:C	F79C	0.989
8:132041139:C:G	R121P	0.988
8:132041150:G:C	C117W	0.987
8:132041152:A:G	C117R	0.984
8:132041567:C:G	C101S	0.984
8:132041568:A:G	C101R	0.984
8:132041568:A:T	C101S	0.984
8:132041151:C:G	C117S	0.983
8:132041152:A:T	C117S	0.983
8:132041573:C:G	C99S	0.982
8:132041574:A:T	C99S	0.982
8:132041632:A:C	F79L	0.981
8:132041632:A:T	F79L	0.981
8:132041634:A:G	F79L	0.981
8:132039087:C:T	C165Y	0.979
8:132041567:C:T	C101Y	0.979
8:132031943:A:C	F323L	0.978
8:132031943:A:T	F323L	0.978
8:132031945:A:G	F323L	0.978
8:132041574:A:G	C99R	0.978
8:132041151:C:T	C117Y	0.977
8:132041529:C:G	D114H	0.977
8:132041566:G:C	C101W	0.976
8:132041577:C:A	G98C	0.976
8:132039086:A:C	C165W	0.973

dbSNP variants (sampled 300 via entrez): RS1000029084 (8:132038531 C>T), RS1000079068 (8:132038500 A>C), RS1000202936 (8:132046798 G>A), RS1000251746 (8:132029889 C>T), RS1000329299 (8:132058766 T>C), RS1000376542 (8:132035823 G>A,T), RS1000381570 (8:132058543 G>T), RS1000409110 (8:132035446 C>T), RS1000532261 (8:132045516 G>C), RS1000542189 (8:132045219 A>G), RS1000568980 (8:132053172 C>T), RS1000629810 (8:132042135 T>G), RS1000633266 (8:132039735 A>G), RS1000710698 (8:132034607 T>C), RS1000715816 (8:132040742 T>C)

Disease associations

OMIM: gene MIM:601658 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002358_4	Pit-and-Fissure caries	4.000000e-06
GCST004691_10	Huntington’s disease progression	3.000000e-06
GCST009391_1779	Metabolite levels	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0010457	Alpha ketoglutarate measurement
EFO:0010480	fumarate measurement
EFO:0010509	maleate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
aflatoxin B2	increases methylation	1
abrine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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