LRFN1

Summary

LRFN1 (leucine rich repeat and fibronectin type III domain containing 1, HGNC:29290) is a protein-coding gene on chromosome 19q13.2, encoding Leucine-rich repeat and fibronectin type III domain-containing protein 1 (Q9P244). Promotes neurite outgrowth in hippocampal neurons.

Predicted to be involved in regulation of postsynaptic density assembly. Predicted to be located in plasma membrane. Predicted to be active in postsynaptic density membrane.

Source: NCBI Gene 57622 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 89 total — 1 likely-pathogenic
• MANE Select transcript: NM_020862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29290
Approved symbol	LRFN1
Name	leucine rich repeat and fibronectin type III domain containing 1
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1484, SALM2
Ensembl gene	ENSG00000128011
Ensembl biotype	protein_coding
OMIM	612807
Entrez	57622

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000248668, ENST00000878521, ENST00000923094, ENST00000923095, ENST00000948095, ENST00000948096, ENST00000948097, ENST00000948098

RefSeq mRNA: 1 — MANE Select: NM_020862 NM_020862

CCDS: CCDS46071

Canonical transcript exons

ENST00000248668 — 5 exons

Exon	Start	End
ENSE00000877747	39313931	39315373
ENSE00001141569	39306566	39308542
ENSE00003057525	39318326	39318358
ENSE00003095219	39320793	39320863
ENSE00003194489	39316082	39316136

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 85.03.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3168 / max 29.9152, expressed in 807 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180849	2.1885	790
180850	0.1283	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	85.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	84.98	gold quality
medial globus pallidus	UBERON:0002477	82.96	gold quality
blood	UBERON:0000178	82.45	gold quality
cortical plate	UBERON:0005343	82.43	gold quality
vena cava	UBERON:0004087	82.29	gold quality
myocardium	UBERON:0002349	82.27	gold quality
globus pallidus	UBERON:0001875	81.31	silver quality
pancreatic ductal cell	CL:0002079	81.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.44	gold quality
cerebellar cortex	UBERON:0002129	80.10	gold quality
cerebellar hemisphere	UBERON:0002245	80.07	gold quality
cerebellum	UBERON:0002037	79.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.39	gold quality
prefrontal cortex	UBERON:0000451	79.32	gold quality
kidney epithelium	UBERON:0004819	79.13	gold quality
right frontal lobe	UBERON:0002810	79.01	gold quality
primary visual cortex	UBERON:0002436	78.77	gold quality
anterior cingulate cortex	UBERON:0009835	78.67	gold quality
frontal cortex	UBERON:0001870	78.62	gold quality
neocortex	UBERON:0001950	78.61	gold quality
nasal cavity epithelium	UBERON:0005384	78.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.50	gold quality
endothelial cell	CL:0000115	78.29	gold quality
entorhinal cortex	UBERON:0002728	78.27	gold quality
granulocyte	CL:0000094	77.98	gold quality
cerebral cortex	UBERON:0000956	77.77	gold quality
thymus	UBERON:0002370	77.77	silver quality
Brodmann (1909) area 23	UBERON:0013554	77.41	gold quality
occipital lobe	UBERON:0002021	77.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting LRFN1, 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-6870-5P	99.99	68.55	2115
HSA-MIR-7152-3P	99.97	67.47	849
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-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6071	99.16	67.77	1780

Literature-anchored findings (GeneRIF, showing 1)

• Identification of a Set of Genes Improving Survival Prediction in Kidney Renal Clear Cell Carcinoma through Integrative Reanalysis of Transcriptomic Data. (PMID:33110456)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrfn1	ENSDARG00000027602
mus_musculus	Lrfn1	ENSMUSG00000030600
rattus_norvegicus	Lrfn1	ENSRNOG00000019869

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), 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 fibronectin type III domain-containing protein 1 — Q9P244 (reviewed: Q9P244)

Alternative names: Synaptic adhesion-like molecule 2

All UniProt accessions (1): Q9P244

UniProt curated annotations — full annotation on UniProt →

Function. Promotes neurite outgrowth in hippocampal neurons. Involved in the regulation and maintenance of excitatory synapses. Induces the clustering of excitatory postsynaptic proteins, including DLG4, DLGAP1, GRIA1 and GRIN1.

Subunit / interactions. Can form heteromeric complexes with LRFN2, LRFN3, LRFN4 and LRFN5. Forms homomeric complexes, but not across cell junctions. Interacts with DLG1, DLG2, DLG3 and DLG4. Interacts with 2 AMPA receptor subunits GRIA1 and GRIA2 and NMDA receptor subunit GRIN1.

Subcellular location. Membrane. Synapse. Postsynaptic density membrane.

Post-translational modifications. Glycosylated.

Domain organisation. The PDZ-binding motif is required for neurite outgrowth promotion and for DLG1-, DLG3- and DLG4-binding.

Similarity. Belongs to the LRFN family.

RefSeq proteins (1): NP_065913* (*=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: PF00041, PF07679, PF13855

UniProt features (25 total): repeat 7, domain 4, region of interest 2, topological domain 2, modified residue 2, glycosylation site 2, signal peptide 1, chain 1, short sequence motif 1, compositionally biased region 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P244-F1	70.70	0.44

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 613, 718

Disulfide bonds (1): 321–370

Glycosylation sites (2): 87, 343

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8849932	Synaptic adhesion-like molecules
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 0 (showing top):

GO Biological Process (1): regulation of postsynaptic density assembly (GO:0099151)

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

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), postsynaptic density membrane (GO:0098839), membrane (GO:0016020), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
postsynaptic density assembly	1
regulation of postsynaptic specialization assembly	1
regulation of excitatory synapse assembly	1
regulation of postsynaptic density organization	1
binding	1
membrane	1
cell periphery	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
cell junction	1
synaptic membrane	1
postsynapse	1

Protein interactions and networks

STRING

944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRFN1	DLG4	P78352	790
LRFN1	NLGN1	Q8N2Q7	600
LRFN1	FN1	P02751	589
LRFN1	DLG1	Q12959	586
LRFN1	DLGAP1	P78335	585
LRFN1	PTPRS	Q13332	543
LRFN1	SOWAHB	A6NEL2	533
LRFN1	LRRTM1	Q86UE6	493
LRFN1	LRRC4C	Q9HCJ2	448
LRFN1	CRTAC1	Q9NQ79	423
LRFN1	STAT2	P52630	414
LRFN1	NPTX1	Q15818	402
LRFN1	IL1RAPL1	Q9NZN1	401
LRFN1	NRXN2	Q9P2S2	400
LRFN1	NRXN1	Q9ULB1	393
LRFN1	LRFN2	Q9ULH4	393

IntAct

160 interactions, top by confidence:

A	B	Type	Score
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
RGS2	LRFN1	psi-mi:“MI:0915”(physical association)	0.550
PTPRD	LRFN1	psi-mi:“MI:0915”(physical association)	0.540
PTPRF	LRFN1	psi-mi:“MI:0915”(physical association)	0.540
LRFN1	PTPRS	psi-mi:“MI:0915”(physical association)	0.540
LRFN1	PTPRD	psi-mi:“MI:0407”(direct interaction)	0.540
LRFN1	PTPRF	psi-mi:“MI:0407”(direct interaction)	0.540
LRFN1	PTPRS	psi-mi:“MI:0407”(direct interaction)	0.540
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
LRFN4	RIMOC1	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
IFNA21	IFIT3	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
CCL14	DNLZ	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530

BioGRID (158): LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS)

ESM2 similar proteins: A2A9Q0, A5PKD8, A9JSM3, D4A2Q0, E7ERA6, F1SAM7, F2Z333, P0CG25, Q07303, Q0IIA6, Q1RMK9, Q24JP5, Q2MJR0, Q2WF71, Q3MIP1, Q3UV16, Q3ZCQ3, Q504Y2, Q5EBM0, Q5GH56, Q5GH64, Q5GH72, Q5RJI4, Q5SZI1, Q641Q3, Q6IEE6, Q6IQX7, Q6P6N5, Q6UKI2, Q6ZMC9, Q6ZVW7, Q86UD0, Q8IUW3, Q8IZ52, Q8K064, Q8N4K4, Q8NAC3, Q8NBR0, Q8NCL9, Q8NFR9

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1KZ92, A2A8L5, A2AJ76, A4IFW2, A4IGL7, A4IIW9, A5JUY8, A7MBJ4, A8WGA3, A8WQH2, B0BNK7, B3A0P3, D2HFT7, D3YXG0, D4A1J9, D4ABX8, G5EBF1, G5EG78, H2A0M7, O15146, O35158, O55005, O89026, P05164, P07202, P09933, P0C6S8, P0C7J6, P11247, P11678, P14650, P16621, P22079, P23468, P35419, P49290, P70193, P80025

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DLG4	“up-regulates activity”	LRFN1	binding
LRFN1	up-regulates	Neurite_outgrowth

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	85
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1298348	NM_020862.2(LRFN1):c.176T>C (p.Val59Ala)	Likely pathogenic

SpliceAI

159 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39308538:TCATC:T	acceptor_gain	1.0000
19:39308539:CATC:C	acceptor_gain	1.0000
19:39308539:CATCC:C	acceptor_gain	1.0000
19:39308543:C:CC	acceptor_gain	1.0000
19:39308540:ATC:A	acceptor_gain	0.9900
19:39308540:ATCCT:A	acceptor_loss	0.9900
19:39308541:TC:T	acceptor_gain	0.9900
19:39308542:CC:C	acceptor_gain	0.9900
19:39308543:CTGT:C	acceptor_loss	0.9900
19:39313929:ACCT:A	donor_loss	0.9800
19:39313930:C:A	donor_loss	0.9800
19:39308545:G:C	acceptor_gain	0.9700
19:39313597:A:C	donor_gain	0.9700
19:39308545:G:GC	acceptor_gain	0.9600
19:39313927:CCACC:C	donor_gain	0.9400
19:39308540:ATCC:A	acceptor_gain	0.9000
19:39308541:TCCT:T	acceptor_gain	0.9000
19:39313913:TGCAG:T	donor_gain	0.8700
19:39308542:CCT:C	acceptor_gain	0.8600
19:39308543:C:A	acceptor_gain	0.8500
19:39313925:ACCC:A	donor_loss	0.8400
19:39308543:C:T	acceptor_gain	0.8200
19:39313929:A:AC	donor_gain	0.7800
19:39313930:C:CC	donor_gain	0.7800
19:39308544:T:A	acceptor_gain	0.7700
19:39308556:CGGG:C	acceptor_gain	0.7400
19:39313959:TGTTG:T	donor_gain	0.7200
19:39313931:C:G	donor_loss	0.7000
19:39313965:A:AC	donor_gain	0.6800
19:39313966:C:CC	donor_gain	0.6800

AlphaMissense

4892 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39314011:C:A	W442C	1.000
19:39314011:C:G	W442C	1.000
19:39314215:A:C	N374K	1.000
19:39314215:A:T	N374K	1.000
19:39314222:G:T	A372D	1.000
19:39314234:A:G	F368S	1.000
19:39314273:A:G	L355P	1.000
19:39314338:C:A	W333C	1.000
19:39314338:C:G	W333C	1.000
19:39314339:C:G	W333S	1.000
19:39314340:A:G	W333R	1.000
19:39314340:A:T	W333R	1.000
19:39314357:G:T	P327H	1.000
19:39314363:C:A	G325V	1.000
19:39314364:C:A	G325C	1.000
19:39314456:A:C	F294C	1.000
19:39314551:C:A	W262C	1.000
19:39314551:C:G	W262C	1.000
19:39314564:C:T	C258Y	1.000
19:39314677:G:C	N220K	1.000
19:39314677:G:T	N220K	1.000
19:39314678:T:A	N220I	1.000
19:39314679:T:A	N220Y	1.000
19:39314693:A:G	L215P	1.000
19:39314749:G:C	N196K	1.000
19:39314749:G:T	N196K	1.000
19:39314759:A:G	L193P	1.000
19:39314765:A:G	L191P	1.000
19:39314821:G:C	N172K	1.000
19:39314821:G:T	N172K	1.000

dbSNP variants (sampled 300 via entrez): RS1000267904 (19:39315805 C>T), RS1001143331 (19:39321648 C>G,T), RS1001277756 (19:39314184 C>T), RS1001584208 (19:39315522 A>T), RS1001594148 (19:39309342 T>A), RS1001646152 (19:39309074 G>A), RS1001678622 (19:39309314 C>A,T), RS1001686223 (19:39318488 T>G), RS1001756461 (19:39321025 A>C,G), RS1001981307 (19:39310263 C>A,T), RS1002012369 (19:39310599 T>C), RS1002210406 (19:39318214 T>A), RS1002853299 (19:39316801 A>C,G), RS1003249521 (19:39319571 A>C), RS1003284493 (19:39318725 C>T)

Disease associations

OMIM: gene MIM:612807 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004744_53	Lung adenocarcinoma	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	6
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Ozone	affects expression, increases abundance	1
Urethane	decreases expression	1
Aflatoxin B1	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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