LRRN3

Summary

LRRN3 (leucine rich repeat neuronal 3, HGNC:17200) is a protein-coding gene on chromosome 7q31.1, encoding Leucine-rich repeat neuronal protein 3 (Q9H3W5).

Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in membrane. Predicted to be active in extracellular matrix and extracellular space.

Source: NCBI Gene 54674 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001099658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17200
Approved symbol	LRRN3
Name	leucine rich repeat neuronal 3
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Aliases	NLRR3, FLJ11129, FIGLER5
Ensembl gene	ENSG00000173114
Ensembl biotype	protein_coding
OMIM	619748
Entrez	54674

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000308478, ENST00000421101, ENST00000422987, ENST00000451085, ENST00000464835, ENST00000961806

RefSeq mRNA: 3 — MANE Select: NM_001099658 NM_001099658, NM_001099660, NM_018334

CCDS: CCDS5754

Canonical transcript exons

ENST00000308478 — 3 exons

Exon	Start	End
ENSE00001550000	111099881	111099962
ENSE00001907739	111122415	111125454
ENSE00003848358	111091127	111091504

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 99.16.

FANTOM5 (CAGE): breadth broad, TPM avg 9.4641 / max 1298.6544, expressed in 747 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80501	7.7716	682
80500	1.4803	352
80502	0.2122	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.16	gold quality
buccal mucosa cell	CL:0002336	96.61	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.35	gold quality
middle temporal gyrus	UBERON:0002771	94.20	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.56	gold quality
substantia nigra pars compacta	UBERON:0001965	92.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.90	gold quality
entorhinal cortex	UBERON:0002728	92.26	gold quality
adrenal tissue	UBERON:0018303	92.25	gold quality
parietal lobe	UBERON:0001872	92.01	gold quality
postcentral gyrus	UBERON:0002581	91.73	gold quality
superior frontal gyrus	UBERON:0002661	91.43	gold quality
occipital lobe	UBERON:0002021	91.21	gold quality
orbitofrontal cortex	UBERON:0004167	91.17	gold quality
primary visual cortex	UBERON:0002436	91.01	gold quality
superior vestibular nucleus	UBERON:0007227	88.57	gold quality
right adrenal gland	UBERON:0001233	88.22	gold quality
adrenal cortex	UBERON:0001235	88.12	gold quality
left adrenal gland	UBERON:0001234	87.93	gold quality
right adrenal gland cortex	UBERON:0035827	87.82	gold quality
adrenal gland	UBERON:0002369	87.57	gold quality
left adrenal gland cortex	UBERON:0035825	87.35	gold quality
CA1 field of hippocampus	UBERON:0003881	86.69	gold quality
prefrontal cortex	UBERON:0000451	86.66	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	86.58	gold quality
ventral tegmental area	UBERON:0002691	86.33	gold quality
nucleus accumbens	UBERON:0001882	86.30	gold quality
lateral globus pallidus	UBERON:0002476	86.27	gold quality
cortical plate	UBERON:0005343	86.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.18	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	7.70
E-GEOD-75140	no	244.74
E-ANND-3	no	4.16
E-GEOD-83139	no	2.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN, PIAS2, ZBTB17

miRNA regulators (miRDB)

52 targeting LRRN3, 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-7110-3P	100.00	73.18	2486
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-4666A-5P	99.41	69.72	1887

Literature-anchored findings (GeneRIF, showing 2)

• NLRR3 is a direct target of MYCN, which associates with Miz-1 and negatively regulates NLRR3 expression. NLRR3 may play a role in NBL differentiation and the survival of NBL patients by inversely correlating with MYCN amplification. (PMID:21908575)
• NLRR3 is proteolytically processed by secretases and its intracellular domain is then released to translocate into the cell nucleus during ATRA-mediated neuroblastoma differentiation. (PMID:25256744)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrn3a	ENSDARG00000077569
danio_rerio	lrrn3b	ENSDARG00000102702
mus_musculus	Lrrn3	ENSMUSG00000036295
rattus_norvegicus	Lrrn3	ENSRNOG00000006368

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), SLITRK1 (ENSG00000178235), GP5 (ENSG00000178732), SLITRK4 (ENSG00000179542), LRRC55 (ENSG00000183908), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

Leucine-rich repeat neuronal protein 3 — Q9H3W5 (reviewed: Q9H3W5)

Alternative names: Neuronal leucine-rich repeat protein 3

All UniProt accessions (3): Q9H3W5, A4D0T1, E7EW58

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (3): NP_001093128, NP_001093130, NP_060804 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF00041, PF07679, PF13855

UniProt features (35 total): repeat 12, glycosylation site 9, domain 4, sequence conflict 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3W5-F1	83.37	0.63

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): 444–496

Glycosylation sites (9): 93, 103, 223, 382, 522, 579, 608, 624, 625

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 215 (showing top): BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, MODULE_255, KAAB_FAILED_HEART_ATRIUM_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, GCANCTGNY_MYOD_Q6, ATACCTC_MIR202, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, MODULE_317, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (1): positive regulation of synapse assembly (GO:0051965)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRN3	GPR15	P49685	571
LRRN3	F2RL3	Q96RI0	554
LRRN3	IMMP2L	Q96T52	521
LRRN3	CLDND1	Q9NY35	507
LRRN3	CD4	P01730	440
LRRN3	CD8A	P01732	437
LRRN3	LRCH4	O75427	435
LRRN3	SASH1	O94885	435
LRRN3	PID1	Q7Z2X4	419
LRRN3	TMEM229A	B2RXF0	396
LRRN3	C10orf62	Q5T681	367
LRRN3	NELL2	Q99435	349
LRRN3	GCNT4	Q9P109	341
LRRN3	VSTM5	A8MXK1	339
LRRN3	DOCK4	Q8N1I0	329
LRRN3	PALLD	Q8WX93	329

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LRRN3	CALML5	psi-mi:“MI:0915”(physical association)	0.560
LRRN3	SERPINB4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): LRRN3 (Affinity Capture-MS), CALML5 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), CALML5 (Affinity Capture-MS)

ESM2 similar proteins: A0N0X6, A4IIW9, B0BLW3, B1H134, B1H234, B4F7C5, D3ZAL8, D3ZTV3, D4A7P2, E5DHB5, F1NUK7, F7D3V9, O43155, O43300, O94898, P58681, Q32Q07, Q3SXY7, Q3URE9, Q504C1, Q50L44, Q52KR2, Q5R482, Q5R6T0, Q5RDJ4, Q61809, Q66HV9, Q6RKD8, Q6UXK5, Q70AK3, Q7L985, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q86VH4, Q86VH5, Q8BGA3, Q8BGT1, Q8BLU0

Diamond homologs: A0N0X6, A2AJ76, A2CG49, A4IGL7, A4IIW9, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, G5EBF1, O75325, O95428, P0C6S8, P11627, P12960, P22063, P28685, P32004, P97924, Q02246, Q07409, Q09024, Q12860, Q290N5, Q32Q07, Q3UQ28, Q3URE9, Q3V1M1, Q5R482, Q61330, Q61809, Q62682, Q62845, Q63198, Q66HV9, Q69Z26, Q6AWJ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

695 predictions. Top by Δscore:

Variant	Effect	Δscore
7:111091503:AG:A	donor_gain	1.0000
7:111091504:GG:G	donor_gain	1.0000
7:111091505:G:GG	donor_gain	1.0000
7:111091505:GT:G	donor_loss	1.0000
7:111099857:T:A	acceptor_gain	1.0000
7:111091272:G:GT	donor_gain	0.9900
7:111091502:AAG:A	donor_gain	0.9900
7:111096731:TAAGA:T	donor_gain	0.9900
7:111096732:AAGAA:A	donor_gain	0.9900
7:111099861:A:AG	acceptor_gain	0.9900
7:111099862:C:G	acceptor_gain	0.9900
7:111099868:A:AG	acceptor_gain	0.9900
7:111099870:A:AG	acceptor_gain	0.9900
7:111099871:T:G	acceptor_gain	0.9900
7:111091501:CAAG:C	donor_gain	0.9800
7:111096772:T:TA	acceptor_gain	0.9800
7:111097274:GGAT:G	donor_gain	0.9800
7:111122393:T:G	acceptor_gain	0.9800
7:111091268:G:GT	donor_gain	0.9700
7:111099873:C:G	acceptor_gain	0.9700
7:111091262:G:GT	donor_gain	0.9600
7:111091500:TCAAG:T	donor_gain	0.9600
7:111091506:T:A	donor_loss	0.9600
7:111099872:A:AG	acceptor_gain	0.9600
7:111099874:A:AG	acceptor_gain	0.9600
7:111099875:A:G	acceptor_gain	0.9600
7:111124660:ATGG:A	donor_gain	0.9600
7:111091263:A:T	donor_gain	0.9500
7:111099869:C:G	acceptor_gain	0.9500
7:111099959:CTGGG:C	donor_loss	0.9500

AlphaMissense

4703 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:111123788:T:C	L339P	0.999
7:111123958:T:A	C396S	0.999
7:111123958:T:C	C396R	0.999
7:111123959:G:A	C396Y	0.999
7:111123959:G:C	C396S	0.999
7:111123960:C:G	C396W	0.999
7:111124029:T:G	C419W	0.999
7:111124034:C:A	P421H	0.999
7:111124260:T:G	C496W	0.999
7:111123562:T:C	F264L	0.998
7:111123564:T:A	F264L	0.998
7:111123564:T:G	F264L	0.998
7:111123572:T:C	L267P	0.998
7:111123729:C:A	N319K	0.998
7:111123729:C:G	N319K	0.998
7:111123886:T:A	C372S	0.998
7:111123886:T:C	C372R	0.998
7:111123887:G:A	C372Y	0.998
7:111123887:G:C	C372S	0.998
7:111123888:T:G	C372W	0.998
7:111123892:T:C	C374R	0.998
7:111123893:G:A	C374Y	0.998
7:111123894:T:G	C374W	0.998
7:111124027:T:C	C419R	0.998
7:111124028:G:A	C419Y	0.998
7:111124034:C:G	P421R	0.998
7:111124102:T:A	C444S	0.998
7:111124102:T:C	C444R	0.998
7:111124103:G:A	C444Y	0.998
7:111124103:G:C	C444S	0.998

dbSNP variants (sampled 300 via entrez): RS1000030769 (7:111095758 A>G,T), RS1000099823 (7:111107746 T>C), RS1000106734 (7:111099158 C>T), RS1000378596 (7:111094164 A>G), RS1000407892 (7:111094441 G>T), RS1000569943 (7:111118895 T>G), RS1000791082 (7:111106441 T>C), RS1000999300 (7:111099543 G>A), RS1000999436 (7:111112425 C>T), RS1001034783 (7:111112121 T>A), RS1001095162 (7:111106108 C>T), RS1001155761 (7:111117670 A>G), RS1001278889 (7:111106957 T>C), RS1001418056 (7:111104676 G>A,C), RS1001475232 (7:111113160 G>A)

Disease associations

OMIM: gene MIM:619748 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004521_25	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004946_10	Schizophrenia	8.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases expression, affects expression, increases reaction	3
Panobinostat	increases expression, affects expression, increases reaction, affects cotreatment	3
Benzo(a)pyrene	affects methylation, increases expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
archazolid B	decreases expression	1
Aripiprazole	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	decreases expression	1
Curcumin	increases expression	1
Cytarabine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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