LRRN1

Summary

LRRN1 (leucine rich repeat neuronal 1, HGNC:20980) is a protein-coding gene on chromosome 3p26.2, encoding Leucine-rich repeat neuronal protein 1 (Q6UXK5).

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. Biomarker of stomach cancer.

Source: NCBI Gene 57633 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 112 total
• MANE Select transcript: NM_020873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20980
Approved symbol	LRRN1
Name	leucine rich repeat neuronal 1
Location	3p26.2
Locus type	gene with protein product
Status	Approved
Aliases	FIGLER3
Ensembl gene	ENSG00000175928
Ensembl biotype	protein_coding
OMIM	619623
Entrez	57633

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000319331, ENST00000472075, ENST00000496115, ENST00000909966, ENST00000934601, ENST00000934602, ENST00000934603, ENST00000934604, ENST00000934605, ENST00000934606, ENST00000934607, ENST00000934608, ENST00000934609, ENST00000934610, ENST00000934611, ENST00000934612

RefSeq mRNA: 3 — MANE Select: NM_020873 NM_001324188, NM_001324189, NM_020873

CCDS: CCDS33685

Canonical transcript exons

ENST00000319331 — 2 exons

Exon	Start	End
ENSE00001259672	3844364	3849834
ENSE00001319947	3799431	3799919

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 88.03.

FANTOM5 (CAGE): breadth broad, TPM avg 18.0982 / max 443.9786, expressed in 718 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35024	15.5453	687
35023	1.0941	439
35025	0.8733	341
35027	0.2210	86
35026	0.1915	96
35028	0.1730	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	88.03	gold quality
ganglionic eminence	UBERON:0004023	85.65	gold quality
dorsal root ganglion	UBERON:0000044	85.00	gold quality
pigmented layer of retina	UBERON:0001782	84.10	gold quality
superior vestibular nucleus	UBERON:0007227	82.53	gold quality
caudate nucleus	UBERON:0001873	82.13	gold quality
pons	UBERON:0000988	81.65	gold quality
putamen	UBERON:0001874	80.67	gold quality
nucleus accumbens	UBERON:0001882	80.59	gold quality
trigeminal ganglion	UBERON:0001675	80.28	gold quality
nasal cavity mucosa	UBERON:0001826	80.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.55	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.38	gold quality
tibia	UBERON:0000979	79.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.11	gold quality
bone marrow cell	CL:0002092	79.08	gold quality
cortical plate	UBERON:0005343	78.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.50	gold quality
prefrontal cortex	UBERON:0000451	78.37	gold quality
amygdala	UBERON:0001876	78.23	gold quality
nasal cavity epithelium	UBERON:0005384	78.12	silver quality
buccal mucosa cell	CL:0002336	77.78	gold quality
anterior cingulate cortex	UBERON:0009835	77.67	gold quality
medulla oblongata	UBERON:0001896	76.56	gold quality
neocortex	UBERON:0001950	76.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.32	gold quality
biceps brachii	UBERON:0001507	76.13	gold quality
cerebral cortex	UBERON:0000956	76.12	gold quality
bronchial epithelial cell	CL:0002328	75.96	gold quality
frontal cortex	UBERON:0001870	75.93	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1013.34
E-MTAB-9388	yes	7.77
E-ANND-3	yes	4.57
E-GEOD-93593	yes	4.28
E-HCAD-5	no	2.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

165 targeting LRRN1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 5)

• N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma. (PMID:18591937)
• NLRR1 appears to be an extracellular negative regulator of ALK signalling in neuroblastoma and neuronal development. (PMID:27604320)
• Authors found that LRRN1 contributes to pluripotency of hESC by preventing translocation of OCT4, NANOG, and SOX2 from nucleus to cytoplasm, thereby lessening their post-translational modification and degradation. (PMID:29893054)
• Study found that LRRN1 is upregulated in gastric cancer (GC) tissue samples and its expression is closely related to poor prognosis. Knocking down LRRN1 expression promoted GC cell apoptosis, and activated the Fas/FasL pathway. (PMID:31087525)
• Whole-genome sequencing identifies variants in ANK1, LRRN1, HAS1, and other genes and regulatory regions for stroke in type 1 diabetes. (PMID:38862513)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrn1	ENSDARG00000060115
mus_musculus	Lrrn1	ENSMUSG00000034648
rattus_norvegicus	Lrrn1	ENSRNOG00000006802

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), 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 1 — Q6UXK5 (reviewed: Q6UXK5)

Alternative names: Neuronal leucine-rich repeat protein 1

All UniProt accessions (1): Q6UXK5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (3): NP_001311117, NP_001311118, NP_065924* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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
IPR050467	LRFN	Family

Pfam: PF07679, PF13855

UniProt features (31 total): repeat 11, domain 4, glycosylation site 4, topological domain 2, compositionally biased region 2, sequence variant 2, signal peptide 1, chain 1, region of interest 1, disulfide bond 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXK5-F1	82.05	0.58

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): 447–499

Glycosylation sites (4): 96, 117, 385, 517

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 194 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, RNGTGGGC_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, AREB6_03, AAGCCAT_MIR135A_MIR135B, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, TATTATA_MIR374, GTTAAAG_MIR302B, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY

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

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRN1	SUMF1	Q8NBK3	501
LRRN1	GAL3ST4	Q96RP7	452
LRRN1	SETMAR	Q53H47	429
LRRN1	SYT14	Q8NB59	424
LRRN1	CRBN	Q96SW2	420
LRRN1	GCNT4	Q9P109	419
LRRN1	TAFA5	Q7Z5A7	412
LRRN1	LRRC4	Q9HBW1	387
LRRN1	LRRC4C	Q9HCJ2	382
LRRN1	LRRC3B	Q96PB8	371
LRRN1	TRNT1	Q96Q11	363
LRRN1	PLXDC2	Q6UX71	343
LRRN1	RTN4R	Q9BZR6	339
LRRN1	IMMP2L	Q96T52	333
LRRN1	FGD5	Q6ZNL6	311

IntAct

33 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
IL13RA2	CHEK1	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TRAF1	LRRN1	psi-mi:“MI:0915”(physical association)	0.560
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
CTLA4	B4GALT5	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LINGO1	LGALS8	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
PDCD6IP	LRRN1	psi-mi:“MI:0407”(direct interaction)	0.440
LRRC4C	LRRN1	psi-mi:“MI:0915”(physical association)	0.400
LRRN1	UNC5A	psi-mi:“MI:0915”(physical association)	0.400
LRRN1	PTPRD	psi-mi:“MI:0914”(association)	0.350
AURKB	VWA8	psi-mi:“MI:0914”(association)	0.350
CD226	TMED7-TICAM2	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CXCR4	ESYT2	psi-mi:“MI:0914”(association)	0.350
DLK1	PLPP3	psi-mi:“MI:0914”(association)	0.350
FPR1	NBAS	psi-mi:“MI:0914”(association)	0.350
LGALS3	SDCBP	psi-mi:“MI:0914”(association)	0.350
LY86	MAP2K7	psi-mi:“MI:0914”(association)	0.350
PMEL	LRRN1	psi-mi:“MI:0914”(association)	0.350
SCN3B	NBAS	psi-mi:“MI:0914”(association)	0.350
SFTPC	CYTH3	psi-mi:“MI:0914”(association)	0.350
SYP	TMEM223	psi-mi:“MI:0914”(association)	0.350
SYT12	APOD	psi-mi:“MI:0914”(association)	0.350
UPK2	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): PTPRD (Affinity Capture-MS), GHITM (Affinity Capture-MS), ST7 (Affinity Capture-MS), LRRN1 (Affinity Capture-RNA), LRRN1 (Two-hybrid), NGEF (Affinity Capture-MS), GHITM (Affinity Capture-MS), PTPRD (Affinity Capture-MS), LRRN1 (Protein-peptide)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	10
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

435 predictions. Top by Δscore:

Variant	Effect	Δscore
3:3799917:GGG:G	donor_gain	0.9800
3:3799918:GG:G	donor_gain	0.9800
3:3799918:GGG:G	donor_gain	0.9800
3:3799919:GG:G	donor_gain	0.9800
3:3799917:GGGGT:G	donor_loss	0.9700
3:3799920:GT:G	donor_loss	0.9700
3:3799921:TAAG:T	donor_loss	0.9700
3:3801221:GC:G	donor_gain	0.9700
3:3799922:AA:A	donor_loss	0.9600
3:3844362:A:AG	acceptor_gain	0.9600
3:3844363:G:GG	acceptor_gain	0.9600
3:3844442:T:G	donor_gain	0.9600
3:3799920:G:GG	donor_gain	0.9500
3:3801244:GCC:G	donor_gain	0.9500
3:3843674:A:AG	acceptor_gain	0.9500
3:3844358:TTTCA:T	acceptor_loss	0.9500
3:3844359:TTCA:T	acceptor_loss	0.9500
3:3844360:TCA:T	acceptor_loss	0.9500
3:3844362:A:C	acceptor_loss	0.9500
3:3844363:G:GC	acceptor_loss	0.9500
3:3844363:GGCAC:G	acceptor_gain	0.9500
3:3801191:TTCTG:T	donor_gain	0.9400
3:3801242:CCGCC:C	donor_gain	0.9400
3:3801243:CGCC:C	donor_gain	0.9400
3:3801244:GCCG:G	donor_gain	0.9400
3:3801247:G:GG	donor_gain	0.9400
3:3801216:C:T	donor_gain	0.9300
3:3799483:C:T	donor_gain	0.9200
3:3799923:AG:A	donor_loss	0.9200
3:3801222:C:G	donor_gain	0.9200

AlphaMissense

4768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:3844771:T:C	F44L	1.000
3:3844772:T:G	F44C	1.000
3:3844773:T:A	F44L	1.000
3:3844773:T:G	F44L	1.000
3:3844813:T:A	C58S	1.000
3:3844813:T:C	C58R	1.000
3:3844814:G:A	C58Y	1.000
3:3844814:G:C	C58S	1.000
3:3844815:C:G	C58W	1.000
3:3844871:T:C	L77P	1.000
3:3844874:T:C	L78P	1.000
3:3844887:T:A	N82K	1.000
3:3844887:T:G	N82K	1.000
3:3844955:A:T	N105I	1.000
3:3844956:C:A	N105K	1.000
3:3844956:C:G	N105K	1.000
3:3845012:T:C	L124P	1.000
3:3845028:T:A	N129K	1.000
3:3845028:T:G	N129K	1.000
3:3845084:T:C	L148P	1.000
3:3845100:C:A	N153K	1.000
3:3845100:C:G	N153K	1.000
3:3845156:T:C	L172P	1.000
3:3845162:T:C	L174P	1.000
3:3845228:T:C	L196P	1.000
3:3845440:T:C	F267L	1.000
3:3845442:C:A	F267L	1.000
3:3845442:C:G	F267L	1.000
3:3844747:T:A	C36S	0.999
3:3844747:T:C	C36R	0.999

dbSNP variants (sampled 300 via entrez): RS1000002496 (3:3814464 G>A), RS1000033847 (3:3814721 G>A), RS1000047155 (3:3824533 C>T), RS1000142493 (3:3846322 A>G), RS1000161019 (3:3836086 C>T), RS1000215092 (3:3808890 CAG>C), RS1000411424 (3:3830144 G>A), RS1000480648 (3:3847873 GA>G,GAA), RS1000490698 (3:3848074 A>G), RS1000534255 (3:3848200 A>C,G), RS1000550244 (3:3815250 C>G,T), RS1000633885 (3:3803801 T>C), RS1000687377 (3:3842212 C>G), RS1000707988 (3:3799315 G>A), RS1000751600 (3:3840889 C>A,G)

Disease associations

OMIM: gene MIM:619623 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002092_2	Callous-unemotional behaviour	4.000000e-06
GCST003820_6	Knee osteoarthritis	8.000000e-06
GCST005042_6	Restless legs syndrome	2.000000e-13
GCST007324_105	Adventurousness	1.000000e-08
GCST008161_117	Waist circumference adjusted for body mass index	8.000000e-06
GCST009368_56	HDL cholesterol levels x long total sleep time interaction (2df test)	8.000000e-09
GCST009391_859	Metabolite levels	4.000000e-06
GCST010002_413	Refractive error	3.000000e-16
GCST010516_2	Fractures (paediatric)	1.000000e-07
GCST90000047_84	Age at first sexual intercourse	2.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005322	callous-unemotional behaviour
EFO:0008579	risk-taking behaviour
EFO:0007789	BMI-adjusted waist circumference
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010533	sorbitol measurement
EFO:0009749	age at first sexual intercourse 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	decreases expression, increases expression, increases methylation	4
trichostatin A	affects cotreatment, decreases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	2
GSK-J4	increases expression	1
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
incobotulinumtoxinA	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	decreases expression, affects cotreatment	1
Glucose	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Nickel	decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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