OLFM3

Summary

OLFM3 (olfactomedin 3, HGNC:17990) is a protein-coding gene on chromosome 1p21.1, encoding Noelin-3 (Q96PB7).

Predicted to be involved in signal transduction. Predicted to be located in Golgi apparatus; extracellular region; and synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in extracellular space.

Source: NCBI Gene 118427 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_058170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17990
Approved symbol	OLFM3
Name	olfactomedin 3
Location	1p21.1
Locus type	gene with protein product
Status	Approved
Aliases	NOE3
Ensembl gene	ENSG00000118733
Ensembl biotype	protein_coding
OMIM	607567
Entrez	118427

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000338858, ENST00000370103, ENST00000462354, ENST00000465523, ENST00000468901, ENST00000536598, ENST00000882547

RefSeq mRNA: 3 — MANE Select: NM_058170 NM_001288821, NM_001288823, NM_058170

CCDS: CCDS30781, CCDS72832

Canonical transcript exons

ENST00000370103 — 6 exons

Exon	Start	End
ENSE00001451798	101802560	101804915
ENSE00001936543	101996748	101996926
ENSE00003513328	101825026	101825245
ENSE00003564079	101830672	101830827
ENSE00003594592	101806076	101806182
ENSE00003673889	101836879	101837025

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 98.11.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7158 / max 1008.5052, expressed in 300 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13559	1.6790	194
13564	1.6592	189
13560	0.4740	158
13565	0.4529	110
13566	0.4147	115
13570	0.3537	122
13562	0.3029	113
13571	0.1198	59
13563	0.1018	39
13567	0.0678	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.27	gold quality
middle temporal gyrus	UBERON:0002771	90.20	gold quality
superior frontal gyrus	UBERON:0002661	89.30	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.15	gold quality
prefrontal cortex	UBERON:0000451	88.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.51	gold quality
frontal cortex	UBERON:0001870	86.87	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.83	gold quality
cortical plate	UBERON:0005343	85.87	gold quality
postcentral gyrus	UBERON:0002581	85.37	gold quality
neocortex	UBERON:0001950	85.27	gold quality
entorhinal cortex	UBERON:0002728	84.85	gold quality
primary visual cortex	UBERON:0002436	84.64	gold quality
parietal lobe	UBERON:0001872	83.66	gold quality
cerebral cortex	UBERON:0000956	83.38	gold quality
right frontal lobe	UBERON:0002810	82.70	gold quality
cerebellar cortex	UBERON:0002129	82.03	gold quality
cerebellum	UBERON:0002037	81.92	gold quality
anterior cingulate cortex	UBERON:0009835	81.92	gold quality
cerebellar hemisphere	UBERON:0002245	81.90	gold quality
occipital lobe	UBERON:0002021	81.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.49	gold quality
substantia nigra pars compacta	UBERON:0001965	80.19	gold quality
pons	UBERON:0000988	79.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.43	gold quality
brain	UBERON:0000955	77.26	gold quality
forebrain	UBERON:0001890	77.00	gold quality
temporal lobe	UBERON:0001871	76.95	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	875.09
E-GEOD-114530	yes	869.94
E-CURD-6	yes	224.55
E-HCAD-35	yes	88.27
E-HCAD-25	yes	85.97
E-ANND-3	yes	4.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX6

miRNA regulators (miRDB)

186 targeting OLFM3, 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-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 3)

• identification of a novel olfactomedin-related gene, named optimedin, located on chromosome 1p21 in humans, expressed in brain and retina; may be a candidate gene for disorders involving the anterior segment of the eye and the retina (optimedin) (PMID:12019210)
• Pax6 regulation of Optimedin in the eye and brain may directly affect multiple developmental processes, including cell migration and axon growth (PMID:16115881)
• This is the first instance of OLFM3 being linked with anoikis resistance in a human cancer cell line (PMID:22281030)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	olfm3b	ENSDARG00000039174
danio_rerio	olfm3a	ENSDARG00000071493
mus_musculus	Olfm3	ENSMUSG00000027965
rattus_norvegicus	Olfm3	ENSRNOG00000017969

Paralogs (9): MYOC (ENSG00000034971), OLFM4 (ENSG00000102837), OLFM2 (ENSG00000105088), OLFML3 (ENSG00000116774), OLFM1 (ENSG00000130558), OLFML2B (ENSG00000162745), OLFML1 (ENSG00000183801), OLFML2A (ENSG00000185585), GLDN (ENSG00000186417)

Protein

Protein identifiers

Noelin-3 — Q96PB7 (reviewed: Q96PB7)

Alternative names: Olfactomedin-3, Optimedin

All UniProt accessions (2): Q96PB7, Q6IMJ0

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including OLFM3. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing. Homodimer. Interacts with MYOC. Interacts with OLFM2.

Subcellular location. Secreted. Synapse.

Tissue specificity. In the eye, expressed in trabecular meshwork and neural retina; in non-ocular tissues, expressed in brain and lung.

Isoforms (6)

UniProt ID	Names	Canonical?
Q96PB7-1	1	yes
Q96PB7-2	2
Q96PB7-3	3
Q96PB7-4	4
Q96PB7-5	5
Q96PB7-6	6

RefSeq proteins (3): NP_001275750, NP_001275752, NP_477518* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003112	Olfac-like_dom	Domain
IPR011044	Quino_amine_DH_bsu	Homologous_superfamily
IPR022082	Noelin_dom	Domain
IPR050605	Olfactomedin-like_domain	Family

Pfam: PF02191, PF12308

UniProt features (16 total): glycosylation site 5, splice variant 4, sequence conflict 2, signal peptide 1, chain 1, domain 1, coiled-coil region 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PB7-F1	78.74	0.48

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 (1): 219–401

Glycosylation sites (5): 33, 95, 179, 299, 465

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): GOBP_NEUROGENESIS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DEVELOPMENT, RIGGI_EWING_SARCOMA_PROGENITOR_UP, chr1p21, GOBP_EYE_MORPHOGENESIS, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_AMPA_GLUTAMATE_RECEPTOR_COMPLEX

GO Biological Process (2): signal transduction (GO:0007165), eye photoreceptor cell development (GO:0042462)

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

GO Cellular Component (5): obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), AMPA glutamate receptor complex (GO:0032281), synapse (GO:0045202), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
eye photoreceptor cell differentiation	1
photoreceptor cell development	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
ionotropic glutamate receptor complex	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OLFM3	MYOC	Q99972	950
OLFM3	FLOT1	O75955	765
OLFM3	OPTN	Q96CV9	587
OLFM3	PTGDS	P41222	584
OLFM3	PAX6	P26367	551
OLFM3	SERPINA3	P01011	493
OLFM3	GRIA1	P42261	474
OLFM3	CALR	P27797	470
OLFM3	CDH4	P55283	459
OLFM3	MAB21L2	Q9Y586	446
OLFM3	CDH13	P55290	395
OLFM3	CALHM3	Q86XJ0	387
OLFM3	EGR2	P11161	371
OLFM3	OTOP1	Q7RTM1	366
OLFM3	PIEZO2	Q9H5I5	364

IntAct

13 interactions, top by confidence:

A	B	Type	Score
PIK3R3	PIK3CD	psi-mi:“MI:0914”(association)	0.800
OLFM3	STUB1	psi-mi:“MI:0915”(physical association)	0.670
STUB1	OLFM3	psi-mi:“MI:0915”(physical association)	0.670
GLRX3	OLFM3	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	OLFM3	psi-mi:“MI:0915”(physical association)	0.560
OLFM3	GLRX3	psi-mi:“MI:0915”(physical association)	0.560
OLFM3	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
OLFM3	OLFM2	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): OLFM3 (Two-hybrid), OLFM3 (Two-hybrid), OLFM3 (Two-hybrid), OLFM2 (Affinity Capture-MS), RNF20 (Affinity Capture-MS), LRP1B (Affinity Capture-MS), EHD4 (Affinity Capture-MS), AGRN (Affinity Capture-MS), OLFM3 (Two-hybrid), OLFM3 (Two-hybrid), DYNLT1 (Two-hybrid), TCF4 (Two-hybrid), OLFM3 (Proximity Label-MS), MYOC (Reconstituted Complex), OLFM3 (Reconstituted Complex)

ESM2 similar proteins: A2BD09, A4IIT5, A6QLD2, O18738, O70624, O75339, O88998, O93279, P05067, P15943, P53601, P63056, P63057, Q06335, Q06481, Q07081, Q0P3W2, Q0V9V5, Q14118, Q14956, Q28685, Q29243, Q29RB4, Q3UZZ4, Q3V1G4, Q5IS80, Q60495, Q62165, Q62609, Q66K08, Q68BL7, Q68BL8, Q6AY06, Q6P7C7, Q6UX06, Q701R2, Q863A3, Q8AXP2, Q8BHP7, Q90372

Diamond homologs: A2BD09, A4IIT5, A6QLD2, B0BNI5, B5MFE9, O70624, O88917, O88923, O88998, O94910, O95490, O95897, O97817, O97827, O97831, P63056, P63057, Q0P3W2, Q0V9V5, Q0VCP3, Q25C36, Q2PT31, Q3UZZ4, Q3V1G4, Q568Y7, Q594P2, Q62609, Q66H86, Q68BL7, Q68BL8, Q6UWY5, Q6UX06, Q80TR1, Q80TS3, Q863A3, Q866N2, Q8BHP7, Q8BK62, Q8BM13, Q8JZZ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3097 predictions. Top by Δscore:

Variant	Effect	Δscore
1:101806041:AATT:A	donor_gain	1.0000
1:101806042:A:C	donor_gain	1.0000
1:101806074:A:AC	donor_gain	1.0000
1:101806075:C:CT	donor_gain	1.0000
1:101806075:CT:C	donor_gain	1.0000
1:101806075:CTCT:C	donor_gain	1.0000
1:101806075:CTCTG:C	donor_gain	1.0000
1:101806178:ACATG:A	acceptor_gain	1.0000
1:101806179:CATG:C	acceptor_gain	1.0000
1:101806179:CATGC:C	acceptor_gain	1.0000
1:101806180:ATG:A	acceptor_gain	1.0000
1:101806180:ATGC:A	acceptor_loss	1.0000
1:101806181:TG:T	acceptor_gain	1.0000
1:101806182:GC:G	acceptor_loss	1.0000
1:101806183:C:A	acceptor_loss	1.0000
1:101806183:C:CC	acceptor_gain	1.0000
1:101806184:T:A	acceptor_loss	1.0000
1:101825024:A:AC	donor_gain	1.0000
1:101825025:C:CC	donor_gain	1.0000
1:101825025:CT:C	donor_gain	1.0000
1:101825025:CTTAG:C	donor_gain	1.0000
1:101825029:G:C	donor_gain	1.0000
1:101830667:CCTA:C	donor_loss	1.0000
1:101830668:CTAC:C	donor_loss	1.0000
1:101830669:TACC:T	donor_loss	1.0000
1:101830670:A:AC	donor_gain	1.0000
1:101830670:A:AG	donor_loss	1.0000
1:101830671:C:CC	donor_gain	1.0000
1:101830827:CCTGT:C	acceptor_loss	1.0000
1:101830828:C:CC	acceptor_gain	1.0000

AlphaMissense

3036 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:101804304:G:C	N457K	1.000
1:101804304:G:T	N457K	1.000
1:101804309:A:G	W456R	1.000
1:101804309:A:T	W456R	1.000
1:101804317:A:T	L453H	1.000
1:101804464:A:G	L404P	1.000
1:101804492:C:A	G395W	1.000
1:101804654:A:G	W341R	1.000
1:101804654:A:T	W341R	1.000
1:101804878:A:T	V266D	1.000
1:101804912:A:G	W255R	1.000
1:101804912:A:T	W255R	1.000
1:101806114:A:G	W241R	1.000
1:101806114:A:T	W241R	1.000
1:101806119:C:T	G239D	1.000
1:101804307:C:A	W456C	0.999
1:101804307:C:G	W456C	0.999
1:101804317:A:G	L453P	0.999
1:101804344:A:G	L444P	0.999
1:101804350:G:A	S442F	0.999
1:101804367:G:C	N436K	0.999
1:101804367:G:T	N436K	0.999
1:101804417:A:C	Y420D	0.999
1:101804472:A:C	C401W	0.999
1:101804473:C:A	C401F	0.999
1:101804473:C:G	C401S	0.999
1:101804473:C:T	C401Y	0.999
1:101804474:A:G	C401R	0.999
1:101804474:A:T	C401S	0.999
1:101804481:G:C	F398L	0.999

dbSNP variants (sampled 300 via entrez): RS1000009665 (1:101831376 G>A), RS1000023449 (1:101849882 T>C), RS1000027158 (1:101932907 T>C), RS1000034291 (1:101893110 G>A), RS1000047142 (1:101924214 A>T), RS1000058375 (1:101932602 G>A,C,T), RS1000060653 (1:101922203 T>G), RS1000081566 (1:101842279 A>G,T), RS1000102256 (1:101955743 C>A), RS1000121613 (1:101979454 A>G), RS1000125447 (1:101810247 A>G), RS1000126941 (1:101938616 G>T), RS1000127575 (1:101927434 C>T), RS1000141003 (1:101973570 C>T), RS1000161625 (1:101877016 T>C)

Disease associations

OMIM: gene MIM:607567 | disease phenotypes: MIM:185100

GenCC curated gene-disease

Mondo (1): strabismus, susceptibility to (MONDO:0008498)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002314_1	Glomerular filtration rate	7.000000e-07
GCST002541_31	Menarche (age at onset)	5.000000e-08
GCST002826_2	Urate levels (BMI interaction)	2.000000e-06
GCST009391_1023	Metabolite levels	7.000000e-07
GCST009391_1699	Metabolite levels	6.000000e-06
GCST012292_9	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	6.000000e-06
GCST012295_6	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	6.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0010361	lysophosphatidylcholine 18:2 measurement
EFO:0010344	cholesteryl ester 18:1 measurement
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	3
methylmercuric chloride	decreases expression	2
trichostatin A	increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	increases methylation	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
mercuric bromide	decreases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
belinostat	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Ethanol	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Folic Acid	affects cotreatment, increases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Acrylamide	decreases expression	1
p-Chloromercuribenzoic Acid	decreases expression	1

Clinical trials (associated diseases)

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