LRRN2

Summary

LRRN2 (leucine rich repeat neuronal 2, HGNC:16914) is a protein-coding gene on chromosome 1q32.1, encoding Leucine-rich repeat neuronal protein 2 (O75325).

The protein encoded by this gene belongs to the leucine-rich repeat superfamily. This gene was found to be amplified and overexpressed in malignant gliomas. The encoded protein has homology with other proteins that function as cell-adhesion molecules or as signal transduction receptors and is a candidate for the target gene in the 1q32.1 amplicon in malignant gliomas. Two alternatively spliced transcript variants encoding the same protein have been described for this gene.

Source: NCBI Gene 10446 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 100 total
• MANE Select transcript: NM_201630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16914
Approved symbol	LRRN2
Name	leucine rich repeat neuronal 2
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	GAC1, LRANK1, FIGLER7
Ensembl gene	ENSG00000170382
Ensembl biotype	protein_coding
OMIM	605492
Entrez	10446

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367175, ENST00000367176, ENST00000367177, ENST00000496057, ENST00000875538, ENST00000875539, ENST00000875540, ENST00000875541, ENST00000875542, ENST00000932704, ENST00000932705, ENST00000941992, ENST00000941993, ENST00000941994

RefSeq mRNA: 2 — MANE Select: NM_201630 NM_006338, NM_201630

CCDS: CCDS1448

Canonical transcript exons

ENST00000367177 — 2 exons

Exon	Start	End
ENSE00001443717	204617170	204620218
ENSE00001443720	204685320	204685738

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 84.68.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2726 / max 106.5982, expressed in 369 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16948	0.8251	288
16947	0.3297	136
16946	0.1178	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	84.68	gold quality
cortical plate	UBERON:0005343	84.13	gold quality
CA1 field of hippocampus	UBERON:0003881	83.90	silver quality
Brodmann (1909) area 10	UBERON:0013541	83.55	silver quality
choroid plexus epithelium	UBERON:0003911	82.93	silver quality
frontal cortex	UBERON:0001870	82.83	gold quality
ventricular zone	UBERON:0003053	82.83	gold quality
nucleus accumbens	UBERON:0001882	82.76	gold quality
adenohypophysis	UBERON:0002196	82.71	gold quality
cingulate cortex	UBERON:0003027	82.64	gold quality
neocortex	UBERON:0001950	82.54	gold quality
anterior cingulate cortex	UBERON:0009835	82.53	gold quality
ganglionic eminence	UBERON:0004023	82.41	gold quality
mucosa of transverse colon	UBERON:0004991	82.03	gold quality
right frontal lobe	UBERON:0002810	81.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.55	gold quality
cerebral cortex	UBERON:0000956	81.43	gold quality
entorhinal cortex	UBERON:0002728	81.23	gold quality
orbitofrontal cortex	UBERON:0004167	81.12	silver quality
superior frontal gyrus	UBERON:0002661	80.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.88	gold quality
telencephalon	UBERON:0001893	80.59	gold quality
hypothalamus	UBERON:0001898	80.51	gold quality
forebrain	UBERON:0001890	80.49	gold quality
pituitary gland	UBERON:0000007	80.35	gold quality
Ammon’s horn	UBERON:0001954	80.29	gold quality
frontal pole	UBERON:0002795	80.11	gold quality
paraflocculus	UBERON:0005351	80.07	gold quality
temporal lobe	UBERON:0001871	79.97	gold quality
amygdala	UBERON:0001876	79.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting LRRN2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3919	99.87	69.45	2489
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-4774-3P	98.90	67.82	737

Literature-anchored findings (GeneRIF, showing 3)

• NLRR2 must be an inducible gene regulated by the JNK pathway to enhance cell survival and inhibit NB cell differentiation. (PMID:27357360)
• Prognostic signatures and potential pathogenesis of eRNAs-related genes in colon adenocarcinoma. (PMID:34622496)
• Up-regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation. (PMID:35894759)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrn2	ENSMUSG00000026443
rattus_norvegicus	Lrrn2	ENSRNOG00000009691

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN3 (ENSG00000173114), 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 2 — O75325 (reviewed: O75325)

Alternative names: Glioma amplified on chromosome 1 protein, Leucine-rich repeat neuronal protein 5

All UniProt accessions (1): O75325

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Overamplified in malignant gliomas.

RefSeq proteins (2): NP_006329, NP_963924* (*=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
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF07679, PF13855

UniProt features (33 total): repeat 12, sequence variant 5, glycosylation site 4, domain 3, sequence conflict 3, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75325-F1	82.49	0.60

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): 445–497

Glycosylation sites (4): 94, 381, 555, 583

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, RNGTGGGC_UNKNOWN, XU_GH1_AUTOCRINE_TARGETS_UP, AP4_Q6, TAL1ALPHAE47_01, RIZKI_TUMOR_INVASIVENESS_3D_DN, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, WTGAAAT_UNKNOWN, HNF4_DR1_Q3, TGACATY_UNKNOWN, SABATES_COLORECTAL_ADENOMA_DN, MULLIGHAN_NPM1_SIGNATURE_3_DN, PTF1BETA_Q6, MULLIGHAN_MLL_SIGNATURE_2_DN

GO Biological Process (2): cell adhesion (GO:0007155), signal transduction (GO:0007165)

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
cellular process	2
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRN2	LRCH4	O75427	433
LRRN2	DHRS13	Q6UX07	397
LRRN2	VSTM5	A8MXK1	380
LRRN2	TMEM81	Q6P7N7	374
LRRN2	PIK3C2B	O00750	369
LRRN2	LRRC1	Q9BTT6	349
LRRN2	GOLT1A	Q6ZVE7	324
LRRN2	OR2T34	Q8NGX1	313
LRRN2	PLEKHA6	Q9Y2H5	312
LRRN2	PPIAL4G	P0DN37	308
LRRN2	OR2T33	Q8NG76	303
LRRN2	IGDCC4	Q8TDY8	301
LRRN2	ENOX1	Q8TC92	299
LRRN2	LRRC56	Q8IYG6	296
LRRN2	LRRC61	Q9BV99	295

IntAct

14 interactions, top by confidence:

A	B	Type	Score
LRRN2	NEUROD4	psi-mi:“MI:0915”(physical association)	0.370
LRRN2	TRIM13	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CLEC4A		psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
LRRN2	F13A1	psi-mi:“MI:0914”(association)	0.350
LCOR	LRRN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): XIAP (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), TRIM13 (Affinity Capture-MS), ETNK1 (Affinity Capture-MS), LRIG3 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), ST7L (Affinity Capture-MS), TRAF2 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), USP22 (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), LRRN2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

735 predictions. Top by Δscore:

Variant	Effect	Δscore
1:204685318:ACC:A	donor_gain	0.9900
1:204685319:CCC:C	donor_gain	0.9900
1:204665171:G:C	acceptor_gain	0.9800
1:204685232:ACG:A	donor_gain	0.9800
1:204685233:CGC:C	donor_gain	0.9800
1:204685318:AC:A	donor_gain	0.9800
1:204685319:CC:C	donor_gain	0.9800
1:204685103:C:A	donor_gain	0.9700
1:204685313:CACT:C	donor_loss	0.9700
1:204685314:ACTC:A	donor_loss	0.9700
1:204685315:CTCA:C	donor_loss	0.9700
1:204685316:TCACC:T	donor_loss	0.9700
1:204685317:C:CC	donor_loss	0.9700
1:204685102:C:CA	donor_gain	0.9600
1:204685318:A:AC	donor_gain	0.9600
1:204685319:C:CC	donor_gain	0.9600
1:204685081:C:CA	donor_gain	0.9500
1:204620134:T:TA	donor_gain	0.9400
1:204665171:G:GC	acceptor_gain	0.9400
1:204685312:ACAC:A	donor_loss	0.9400
1:204685140:T:TA	donor_gain	0.9300
1:204685197:C:CA	donor_gain	0.9300
1:204685318:ACCC:A	donor_gain	0.9200
1:204685319:CCCC:C	donor_gain	0.9200
1:204636107:TTAA:T	donor_gain	0.9100
1:204636108:TAAT:T	donor_gain	0.9100
1:204636109:AATA:A	donor_gain	0.9100
1:204685087:C:CA	donor_gain	0.9100
1:204684963:TC:T	donor_gain	0.9000
1:204685233:CG:C	donor_gain	0.9000

AlphaMissense

4584 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:204619340:A:G	L218P	1.000
1:204619412:A:G	L194P	1.000
1:204619421:A:C	L191W	1.000
1:204619484:A:G	L170P	1.000
1:204618622:C:A	W457C	0.999
1:204618622:C:G	W457C	0.999
1:204618803:C:G	C397S	0.999
1:204618804:A:T	C397S	0.999
1:204618856:C:A	W379C	0.999
1:204618856:C:G	W379C	0.999
1:204618974:A:G	L340P	0.999
1:204619033:G:C	N320K	0.999
1:204619033:G:T	N320K	0.999
1:204619190:A:G	L268P	0.999
1:204619196:A:G	L266P	0.999
1:204619198:G:C	F265L	0.999
1:204619198:G:T	F265L	0.999
1:204619199:A:C	F265C	0.999
1:204619200:A:G	F265L	0.999
1:204619367:A:G	F209S	0.999
1:204619396:G:C	N199K	0.999
1:204619396:G:T	N199K	0.999
1:204619412:A:T	L194H	0.999
1:204619468:G:C	N175K	0.999
1:204619468:G:T	N175K	0.999
1:204619478:A:G	L172P	0.999
1:204619493:A:C	L167W	0.999
1:204619540:G:C	N151K	0.999
1:204619540:G:T	N151K	0.999
1:204619541:T:A	N151I	0.999

dbSNP variants (sampled 300 via entrez): RS1000083764 (1:204645798 A>T), RS1000139022 (1:204672455 G>A), RS1000241757 (1:204631526 A>G), RS1000259079 (1:204622382 C>T), RS1000435995 (1:204616855 T>A,G), RS1000447223 (1:204657702 T>C), RS1000465883 (1:204650249 G>A), RS1000479885 (1:204657459 T>C), RS1000486177 (1:204682710 C>A,G), RS1000493328 (1:204657994 T>C), RS1000528844 (1:204684535 G>A), RS1000559616 (1:204639872 G>T), RS1000581031 (1:204643296 G>A), RS1000657313 (1:204665057 G>A,T), RS1000685042 (1:204644635 C>T)

Disease associations

OMIM: gene MIM:605492 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001930_14	Breast cancer	2.000000e-12
GCST001942_20	Prostate cancer	2.000000e-11
GCST002045_3	Educational attainment	8.000000e-12
GCST002875_72	Diisocyanate-induced asthma	1.000000e-06
GCST005141_46	Cognitive ability (MTAG)	2.000000e-09
GCST005316_312	Intelligence (MTAG)	2.000000e-10
GCST006922_4	Regular attendance at a religious group	3.000000e-08
GCST008595_17	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-16
GCST008647_44	Urinary sodium excretion	3.000000e-09
GCST009523_3	Household income	1.000000e-08
GCST009524_203	Household income (MTAG)	6.000000e-09
GCST009524_232	Household income (MTAG)	4.000000e-17
GCST010135_42	Oily fish consumption	2.000000e-08
GCST010140_32	Pork consumption	2.000000e-08
GCST010142_21	Fish- and plant-related diet	9.000000e-10
GCST90006922_1	Polyomavirus 2 JC VP1 antibody levels	2.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0006995	response to diisocyanate
EFO:0004337	intelligence
EFO:0009592	social interaction measurement
EFO:0009282	sodium measurement
EFO:0009695	household income
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Cytarabine	decreases expression	1
Estradiol	increases expression	1
Dronabinol	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation, decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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