LRRN4

Summary

LRRN4 (leucine rich repeat neuronal 4, HGNC:16208) is a protein-coding gene on chromosome 20p12.3, encoding Leucine-rich repeat neuronal protein 4 (Q8WUT4). May play an important role in hippocampus-dependent long-lasting memory.

Predicted to be involved in long-term memory. Predicted to act upstream of or within visual learning. Located in extracellular exosome.

Source: NCBI Gene 164312 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 137 total — 1 pathogenic
• MANE Select transcript: NM_152611

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16208
Approved symbol	LRRN4
Name	leucine rich repeat neuronal 4
Location	20p12.3
Locus type	gene with protein product
Status	Approved
Aliases	dJ1056H1.1, NLRR4
Ensembl gene	ENSG00000125872
Ensembl biotype	protein_coding
OMIM	619706
Entrez	164312

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000378858, ENST00000698795, ENST00000698796, ENST00000698797, ENST00000903106, ENST00000923518, ENST00000943038

RefSeq mRNA: 1 — MANE Select: NM_152611 NM_152611

CCDS: CCDS13097

Canonical transcript exons

ENST00000378858 — 5 exons

Exon	Start	End
ENSE00001211290	6044543	6044680
ENSE00001211295	6050779	6050983
ENSE00001211312	6040546	6042246
ENSE00001479051	6052145	6052804
ENSE00001479056	6053830	6054060

Expression profiles

Bgee: expression breadth broad, 78 present calls, max score 89.67.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6900 / max 280.1698, expressed in 317 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186358	1.2251	174
186359	0.4899	114
186342	0.2154	110
186355	0.1971	74
186360	0.0779	39
186347	0.0649	31
186353	0.0620	22
186343	0.0560	23
186357	0.0537	29
186341	0.0381	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.67	gold quality
germinal epithelium of ovary	UBERON:0001304	85.06	gold quality
oocyte	CL:0000023	78.15	gold quality
parietal pleura	UBERON:0002400	78.12	gold quality
secondary oocyte	CL:0000655	77.34	gold quality
upper lobe of left lung	UBERON:0008952	76.90	gold quality
upper lobe of lung	UBERON:0008948	76.30	gold quality
right lung	UBERON:0002167	74.32	gold quality
lung	UBERON:0002048	71.04	gold quality
omental fat pad	UBERON:0010414	69.14	gold quality
peritoneum	UBERON:0002358	69.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	67.62	gold quality
metanephros cortex	UBERON:0010533	67.61	gold quality
lower lobe of lung	UBERON:0008949	65.84	silver quality
visceral pleura	UBERON:0002401	62.00	gold quality
metanephros	UBERON:0000081	61.89	gold quality
adult mammalian kidney	UBERON:0000082	59.63	gold quality
cortex of kidney	UBERON:0001225	59.32	gold quality
islet of Langerhans	UBERON:0000006	56.83	gold quality
pancreas	UBERON:0001264	56.43	gold quality
body of pancreas	UBERON:0001150	56.37	gold quality
kidney	UBERON:0002113	56.29	gold quality
pericardium	UBERON:0002407	56.17	gold quality
cerebellar vermis	UBERON:0004720	54.43	gold quality
seminal vesicle	UBERON:0000998	53.98	gold quality
decidua	UBERON:0002450	53.79	gold quality
nucleus accumbens	UBERON:0001882	53.69	gold quality
nasal cavity mucosa	UBERON:0001826	50.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	50.48	gold quality
putamen	UBERON:0001874	50.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting LRRN4, 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-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-591	96.29	68.16	611
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-7704	95.30	62.35	115

Literature-anchored findings (GeneRIF, showing 1)

• LRRN4 was only detected in primary mesothelial cells, but MSLN and UPK3B were also detected in other cell types. (PMID:21984916)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrn4	ENSMUSG00000043110
rattus_norvegicus	Lrrn4	ENSRNOG00000032989

Paralogs (3): ISLR (ENSG00000129009), ISLR2 (ENSG00000167178), LRRN4CL (ENSG00000177363)

Protein

Protein identifiers

Leucine-rich repeat neuronal protein 4 — Q8WUT4 (reviewed: Q8WUT4)

Alternative names: Neuronal leucine-rich repeat protein 4

All UniProt accessions (3): Q8WUT4, A0A8V8TP10, Q6ZMD1

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in hippocampus-dependent long-lasting memory.

Subcellular location. Membrane.

RefSeq proteins (1): NP_689824* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily

Pfam: PF00041, PF13855

UniProt features (27 total): repeat 10, glycosylation site 6, compositionally biased region 2, topological domain 2, sequence variant 2, signal peptide 1, chain 1, domain 1, region of interest 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUT4-F1	69.64	0.37

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 (6): 42, 176, 289, 379, 442, 622

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_ASSOCIATIVE_LEARNING, GOBP_LEARNING, GOBP_RESPONSE_TO_RADIATION, GOBP_LONG_TERM_MEMORY, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, WANG_RESPONSE_TO_FORSKOLIN_UP, GOBP_VISUAL_BEHAVIOR, WANG_RESPONSE_TO_ANDROGEN_UP, GOBP_RESPONSE_TO_LIGHT_STIMULUS, JOHNSTONE_PARVB_TARGETS_3_DN, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP

GO Biological Process (2): long-term memory (GO:0007616), visual learning (GO:0008542)

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

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
memory	1
visual behavior	1
associative learning	1
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRN4	PMS2P11	Q13670	642
LRRN4	MSLN	Q13421	453
LRRN4	NKAIN4	Q8IVV8	447
LRRN4	GPM6A	P51674	428
LRRN4	HIGD1B	Q9P298	403
LRRN4	C12orf60	Q5U649	359
LRRN4	CST9L	Q9H4G1	343
LRRN4	PDLIM3	Q53GG5	325
LRRN4	PAPSS2	O95340	319
LRRN4	G5EA03	G5EA03	304
LRRN4	MTMR4	Q9NYA4	300
LRRN4	FIG4	Q92562	296
LRRN4	CLEC3B	P05452	293
LRRN4	IQCF1	Q8N6M8	292
LRRN4	ACSF3	Q4G176	290

IntAct

17 interactions, top by confidence:

A	B	Type	Score
DZIP1L	LRRN4	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	LRRN4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	LRRN4	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LRRN4	psi-mi:“MI:0915”(physical association)	0.560
LRRN4	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
MDFI	LRRN4	psi-mi:“MI:0915”(physical association)	0.370
LRRN4	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
LRRN4	DZIP1L	psi-mi:“MI:0915”(physical association)	0.000
LRRN4	HSF2BP	psi-mi:“MI:0915”(physical association)	0.000
LRRN4	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
LRRN4	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): LRRN4 (Two-hybrid), DZIP1L (Two-hybrid), HSF2BP (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP3-3 (Two-hybrid), LRRN4 (Affinity Capture-MS), LRRN4 (Protein-peptide), LRRN4 (Co-fractionation), LRRN4 (Co-fractionation), LRRN4 (Co-fractionation)

ESM2 similar proteins: A4FV93, A5A8Y8, B2LW77, D3ZUK3, O00468, O70534, O75074, O88204, O88839, O95407, P06579, P07204, P15306, P60882, P80370, Q09163, Q13444, Q14162, Q3SWY4, Q501P1, Q53RD9, Q5ND28, Q5VY43, Q5W7P8, Q61810, Q6AZ60, Q6GUQ1, Q6MG84, Q6UY11, Q71U07, Q75N90, Q7Z7M0, Q8K1E3, Q8K1S7, Q8K4G1, Q8NCW0, Q8ND94, Q8VIK5, Q8WUT4, Q93038

Diamond homologs: A8WHP9, B0M0P8, B1H234, D3ZTV3, F1NUK7, F4J7T6, O02678, O35103, O35367, O42235, O43155, O46377, O46378, O46379, O46390, O46403, O60938, O62702, O77742, O81825, O94769, P0DV53, P12024, P13605, P19879, P20774, P21809, P21810, P28653, P28654, P47853, P50608, P50609, P51884, P51885, P51886, P51887, P51890, P59383, Q05443

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	121
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
831757	NC_000020.10:g.(?6015110)(6759736_?)del	Pathogenic

SpliceAI

567 predictions. Top by Δscore:

Variant	Effect	Δscore
20:6050777:A:AC	donor_gain	1.0000
20:6050778:C:CC	donor_gain	1.0000
20:6050778:CTT:C	donor_gain	1.0000
20:6044676:TGCAG:T	acceptor_gain	0.9900
20:6044678:CAG:C	acceptor_gain	0.9900
20:6044678:CAGCT:C	acceptor_loss	0.9900
20:6044680:GC:G	acceptor_loss	0.9900
20:6044681:C:CC	acceptor_gain	0.9900
20:6044681:CTGAA:C	acceptor_loss	0.9900
20:6044682:T:G	acceptor_loss	0.9900
20:6050772:CACTT:C	donor_loss	0.9900
20:6050773:ACTTA:A	donor_loss	0.9900
20:6050775:TTA:T	donor_loss	0.9900
20:6050776:TA:T	donor_loss	0.9900
20:6050979:CTCAA:C	acceptor_gain	0.9900
20:6050981:CAA:C	acceptor_gain	0.9900
20:6050984:C:CC	acceptor_gain	0.9900
20:6052143:AC:A	donor_gain	0.9900
20:6052143:ACC:A	donor_gain	0.9900
20:6052144:CC:C	donor_gain	0.9900
20:6052144:CCC:C	donor_gain	0.9900
20:6053825:CTTA:C	donor_loss	0.9900
20:6053826:TTAC:T	donor_loss	0.9900
20:6053827:TACCT:T	donor_loss	0.9900
20:6053828:A:T	donor_loss	0.9900
20:6042451:C:CC	acceptor_gain	0.9800
20:6044537:TGTTA:T	donor_loss	0.9800
20:6044538:GTTAC:G	donor_loss	0.9800
20:6044539:TTACC:T	donor_loss	0.9800
20:6044540:TACCT:T	donor_loss	0.9800

AlphaMissense

4719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:6041445:C:A	W600C	0.993
20:6041445:C:G	W600C	0.993
20:6041447:A:G	W600R	0.988
20:6041447:A:T	W600R	0.988
20:6052474:T:A	N109I	0.986
20:6052405:T:A	N132I	0.985
20:6052404:G:C	N132K	0.983
20:6052404:G:T	N132K	0.983
20:6041306:A:C	Y647D	0.981
20:6044677:G:C	C288W	0.981
20:6041417:A:C	Y610D	0.978
20:6041497:G:T	P583H	0.978
20:6044608:G:C	N311K	0.978
20:6044608:G:T	N311K	0.978
20:6052406:T:A	N132Y	0.978
20:6052473:G:C	N109K	0.976
20:6052473:G:T	N109K	0.976
20:6041536:C:G	C570S	0.975
20:6041537:A:T	C570S	0.975
20:6042229:C:G	C339S	0.975
20:6042230:A:T	C339S	0.975
20:6052332:A:C	N156K	0.975
20:6052332:A:T	N156K	0.975
20:6052545:G:C	N85K	0.975
20:6052545:G:T	N85K	0.975
20:6041452:A:T	V598D	0.974
20:6052475:T:A	N109Y	0.974
20:6050972:A:G	W223R	0.973
20:6050972:A:T	W223R	0.973
20:6041462:A:G	S595P	0.972

dbSNP variants (sampled 300 via entrez): RS1000180547 (20:6047585 G>T), RS1000200042 (20:6047237 C>A,G), RS1000266386 (20:6044273 T>C), RS1000312792 (20:6049591 C>T), RS1000871629 (20:6045752 G>T), RS1001022712 (20:6040057 A>G), RS1001469610 (20:6052082 G>A,C), RS1001629565 (20:6054449 AGTTT>A), RS1001696102 (20:6054916 G>A,C,T), RS1001769082 (20:6043902 T>C), RS1002147031 (20:6054574 G>C), RS1002209650 (20:6050185 C>T), RS1002373505 (20:6045307 G>A), RS1002811517 (20:6045034 A>T), RS1002835018 (20:6048102 T>G)

Disease associations

OMIM: gene MIM:619706 | 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
GCST009615_19	Triglyceride levels x loop diuretics use interaction	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	4
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	affects expression, increases expression	2
aminomethylphosphonic acid (AMPA)	decreases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
trichostatin A	increases expression	1
1,6-hexamethylene diisocyanate	increases methylation	1
mercuric bromide	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
monomethylarsonous acid	decreases 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	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Panobinostat	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Cytarabine	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Smoke	increases expression	1
Urethane	decreases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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