LRTM2

Summary

LRTM2 (leucine rich repeat transmembrane protein 2, HGNC:32443) is a protein-coding gene on chromosome 12p13.33, encoding Leucine-rich repeat and transmembrane domain-containing protein 2 (Q8N967).

Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in membrane.

Source: NCBI Gene 654429 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001039029

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32443
Approved symbol	LRTM2
Name	leucine rich repeat transmembrane protein 2
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166159
Ensembl biotype	protein_coding
OMIM	621359
Entrez	654429

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding_CDS_not_defined, 5 protein_coding

ENST00000299194, ENST00000535041, ENST00000539859, ENST00000540378, ENST00000542529, ENST00000543694, ENST00000543730, ENST00000543818, ENST00000544489, ENST00000545157, ENST00000546157, ENST00000546167

RefSeq mRNA: 3 — MANE Select: NM_001039029 NM_001039029, NM_001163925, NM_001163926

CCDS: CCDS31726

Canonical transcript exons

ENST00000299194 — 5 exons

Exon	Start	End
ENSE00001100311	1830935	1831525
ENSE00001239977	1827410	1827594
ENSE00001239981	1820565	1820814
ENSE00003668273	1828076	1828215
ENSE00003842486	1834267	1836753

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 86.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1892 / max 84.8059, expressed in 102 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123402	0.4270	86
123403	0.4241	83
123401	0.1394	57
123400	0.1064	56
123404	0.0752	45
123405	0.0172	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
putamen	UBERON:0001874	86.99	gold quality
superior frontal gyrus	UBERON:0002661	86.36	gold quality
caudate nucleus	UBERON:0001873	85.17	gold quality
primary visual cortex	UBERON:0002436	84.91	gold quality
prefrontal cortex	UBERON:0000451	84.58	gold quality
frontal cortex	UBERON:0001870	84.58	gold quality
right frontal lobe	UBERON:0002810	84.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.28	gold quality
nucleus accumbens	UBERON:0001882	81.42	gold quality
cerebral cortex	UBERON:0000956	81.23	gold quality
anterior cingulate cortex	UBERON:0009835	80.05	gold quality
hypothalamus	UBERON:0001898	75.79	gold quality
cortical plate	UBERON:0005343	75.53	gold quality
temporal lobe	UBERON:0001871	75.47	gold quality
amygdala	UBERON:0001876	75.16	gold quality
ganglionic eminence	UBERON:0004023	73.22	gold quality
brain	UBERON:0000955	73.02	gold quality
Ammon’s horn	UBERON:0001954	72.87	gold quality
substantia nigra	UBERON:0002038	62.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	57.72	gold quality
cerebellum	UBERON:0002037	56.19	gold quality
cerebellar cortex	UBERON:0002129	56.00	gold quality
cerebellar hemisphere	UBERON:0002245	55.93	gold quality
ventricular zone	UBERON:0003053	54.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	50.87	gold quality
corpus callosum	UBERON:0002336	47.68	gold quality
bone marrow cell	CL:0002092	43.70	gold quality
colonic epithelium	UBERON:0000397	42.39	gold quality
granulocyte	CL:0000094	42.34	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting LRTM2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-361-3P	99.19	66.45	1381

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrtm2a	ENSDARG00000045483
danio_rerio	zgc:153913	ENSDARG00000063518
mus_musculus	Lrtm2	ENSMUSG00000055003
rattus_norvegicus	Lrtm2	ENSRNOG00000007508

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), 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 and transmembrane domain-containing protein 2 — Q8N967 (reviewed: Q8N967)

All UniProt accessions (3): Q8N967, F5GZY9, F5H2B4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (3): NP_001034118, NP_001157397, NP_001157398 (=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
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF01462, PF13855

UniProt features (19 total): repeat 5, glycosylation site 4, domain 2, region of interest 2, topological domain 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N967-F1	80.38	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.

Glycosylation sites (4): 90, 117, 125, 257

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, 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, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS

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

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

GO Cellular Component (1): 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
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRTM2	CACNA2D4	Q7Z3S7	582
LRTM2	TEX52	A6NCN8	528
LRTM2	FBXL14	Q8N1E6	511
LRTM2	NINJ2	Q9NZG7	435
LRTM2	ERC1	Q8IUD2	419
LRTM2	INSYN2A	Q6ZSG2	406
LRTM2	ZNF280D	Q6N043	389
LRTM2	B4GALNT3	Q6L9W6	374
LRTM2	ITFG2	Q969R8	370
LRTM2	DCP1B	Q8IZD4	370
LRTM2	WNK1	P54963	354
LRTM2	NKAIN3	Q8N8D7	354
LRTM2	TMTC4	Q5T4D3	351
LRTM2	CCDC60	Q8IWA6	350
LRTM2	CCDC178	Q5BJE1	346

IntAct

3 interactions, top by confidence:

A	B	Type	Score
LRTM2	ABCC4	psi-mi:“MI:0914”(association)	0.350
INO80	ACTL6B	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): BLK (Affinity Capture-MS), SLC27A3 (Affinity Capture-MS), ALG14 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), LRTM2 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ZDHHC6 (Affinity Capture-MS), LRTM2 (Positive Genetic), LRTM2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A3KNN3, A4IFA6, A6H789, A6H793, A6NDA9, A8WHP9, E7FE13, O08644, O08742, O08770, O14498, O15197, P0C0K6, P0C0K7, P14616, P14617, P21709, P54760, P54761, P59034, P59035, Q149C3, Q3ZBI5, Q5BK65, Q5JZY3, Q5NVQ6, Q5R7M3, Q60750, Q62178, Q64716, Q6GU68, Q6P7C4, Q6PFC5, Q6UY18, Q80ZD5, Q86SJ2, Q86WK7, Q86YC3, Q8BGX3, Q8BMT4

Diamond homologs: A2ARI4, A8WHP9, B0BLW3, D4AC13, E5DHB5, E7FE13, F1MLX5, F1MT22, F7D3V9, O02833, O75473, P0DM44, P70193, Q3UVD5, Q5NVQ6, Q8BGX3, Q8N967, Q96JA1, Q9BXB1, Q9HBX8, Q9Z1P4, Q9Z2H4, A3KNN3, A4IIW9, A6H789, A6H793, A6NJW4, C3YZ59, G5EFX6, O02678, O14498, O35367, O42235, O46542, O60938, O62702, O75093, O75094, O88186, O88279

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1433 predictions. Top by Δscore:

Variant	Effect	Δscore
12:1830915:C:A	acceptor_gain	1.0000
12:1830919:T:A	acceptor_gain	1.0000
12:1830931:CAA:C	acceptor_loss	1.0000
12:1830932:AAG:A	acceptor_gain	1.0000
12:1830932:AAGG:A	acceptor_gain	1.0000
12:1830933:A:AT	acceptor_loss	1.0000
12:1830933:A:G	acceptor_gain	1.0000
12:1834262:T:G	acceptor_gain	1.0000
12:1834265:AG:A	acceptor_gain	1.0000
12:1834265:AGGGG:A	acceptor_gain	1.0000
12:1834266:GG:G	acceptor_gain	1.0000
12:1834266:GGGGG:G	acceptor_gain	1.0000
12:1820378:GG:G	donor_gain	0.9900
12:1820379:GG:G	donor_gain	0.9900
12:1820810:GACGG:G	donor_gain	0.9900
12:1820813:GG:G	donor_gain	0.9900
12:1820814:GG:G	donor_gain	0.9900
12:1830929:A:AG	acceptor_gain	0.9900
12:1830930:C:G	acceptor_gain	0.9900
12:1830932:A:AG	acceptor_gain	0.9900
12:1830933:AG:A	acceptor_gain	0.9900
12:1830933:AGG:A	acceptor_gain	0.9900
12:1830934:G:A	acceptor_gain	0.9900
12:1830934:G:GC	acceptor_gain	0.9900
12:1830934:GGG:G	acceptor_gain	0.9900
12:1830934:GGGA:G	acceptor_gain	0.9900
12:1831523:GAGGT:G	donor_loss	0.9900
12:1831524:AGG:A	donor_loss	0.9900
12:1831525:GG:G	donor_loss	0.9900
12:1831526:GTGAG:G	donor_loss	0.9900

AlphaMissense

2405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:1831467:G:C	W200C	1.000
12:1831467:G:T	W200C	1.000
12:1831173:C:A	N102K	0.999
12:1831173:C:G	N102K	0.999
12:1831245:C:A	N126K	0.999
12:1831245:C:G	N126K	0.999
12:1831317:C:A	N150K	0.999
12:1831317:C:G	N150K	0.999
12:1831459:A:T	N198Y	0.999
12:1831461:C:A	N198K	0.999
12:1831461:C:G	N198K	0.999
12:1831465:T:A	W200R	0.999
12:1831465:T:C	W200R	0.999
12:1831471:T:A	C202S	0.999
12:1831472:G:C	C202S	0.999
12:1831503:G:C	W212C	0.999
12:1831503:G:T	W212C	0.999
12:1834290:T:A	C228S	0.999
12:1834290:T:C	C228R	0.999
12:1834291:G:A	C228Y	0.999
12:1834291:G:C	C228S	0.999
12:1834292:C:G	C228W	0.999
12:1834348:T:G	F247C	0.999
12:1834572:T:C	C322R	0.999
12:1834582:T:A	M325K	0.999
12:1831163:T:C	L99P	0.998
12:1831171:A:T	N102Y	0.998
12:1831229:T:C	L121P	0.998
12:1831243:A:T	N126Y	0.998
12:1831301:T:C	L145P	0.998

dbSNP variants (sampled 300 via entrez): RS1000198033 (12:1820719 C>A,T), RS1000234980 (12:1828777 C>T), RS1000250575 (12:1820500 G>A,C,T), RS1000403761 (12:1833047 T>G), RS1000405188 (12:1825436 G>A,T), RS1000540553 (12:1835620 G>A), RS1001115538 (12:1837027 A>G,T), RS1001581618 (12:1833132 C>T), RS1001641302 (12:1832705 G>A), RS1001744792 (12:1828397 C>G,T), RS1001754769 (12:1828274 T>C), RS1001794469 (12:1832980 T>G), RS1001937006 (12:1820499 C>A,G,T), RS1001985147 (12:1824747 C>A,G,T), RS1002021372 (12:1828743 G>A)

Disease associations

OMIM: gene MIM:621359 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	decreases methylation	1
perfluorobutanesulfonic acid	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Methapyrilene	decreases methylation	1
Rotenone	decreases expression	1
Testosterone	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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