LRRC1

Summary

LRRC1 (leucine rich repeat containing 1, HGNC:14307) is a protein-coding gene on chromosome 6p12.1, encoding Leucine-rich repeat-containing protein 1 (Q9BTT6).

Located in cytosol.

Source: NCBI Gene 55227 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_018214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14307
Approved symbol	LRRC1
Name	leucine rich repeat containing 1
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ523E19.1, LANO, FLJ10775, FLJ11834
Ensembl gene	ENSG00000137269
Ensembl biotype	protein_coding
OMIM	608195
Entrez	55227

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000370882, ENST00000370888, ENST00000487251, ENST00000490222, ENST00000960208

RefSeq mRNA: 1 — MANE Select: NM_018214 NM_018214

CCDS: CCDS4953

Canonical transcript exons

ENST00000370888 — 14 exons

Exon	Start	End
ENSE00000929869	53897285	53897359
ENSE00001015692	53920625	53920761
ENSE00001015693	53913854	53913969
ENSE00001015694	53919498	53919670
ENSE00001084228	53904379	53904462
ENSE00001453839	53922635	53924125
ENSE00001453846	53795005	53795415
ENSE00002167721	53878993	53879071
ENSE00002168740	53896829	53896892
ENSE00002174135	53842110	53842227
ENSE00002178981	53896498	53896554
ENSE00002198809	53882887	53882976
ENSE00003576678	53902629	53902747
ENSE00003658939	53899747	53899891

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 95.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8753 / max 379.9191, expressed in 1372 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68264	4.6034	1317
68266	1.0338	557
68267	0.5946	334
68270	0.3616	77
68265	0.1578	74
68268	0.1240	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	95.62	gold quality
colonic mucosa	UBERON:0000317	95.47	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.27	gold quality
amniotic fluid	UBERON:0000173	93.47	gold quality
jejunal mucosa	UBERON:0000399	92.67	gold quality
oviduct epithelium	UBERON:0004804	92.29	gold quality
palpebral conjunctiva	UBERON:0001812	92.12	gold quality
esophagus squamous epithelium	UBERON:0006920	92.03	gold quality
mucosa of transverse colon	UBERON:0004991	91.74	gold quality
hair follicle	UBERON:0002073	91.47	gold quality
rectum	UBERON:0001052	91.46	gold quality
skin of leg	UBERON:0001511	91.02	gold quality
skin of abdomen	UBERON:0001416	90.81	gold quality
squamous epithelium	UBERON:0006914	90.75	gold quality
secondary oocyte	CL:0000655	90.57	gold quality
zone of skin	UBERON:0000014	90.51	gold quality
vagina	UBERON:0000996	90.27	gold quality
parotid gland	UBERON:0001831	90.10	gold quality
epithelium of esophagus	UBERON:0001976	90.10	gold quality
buccal mucosa cell	CL:0002336	90.07	gold quality
ectocervix	UBERON:0012249	89.96	gold quality
oral cavity	UBERON:0000167	89.90	gold quality
lower esophagus mucosa	UBERON:0035834	89.77	gold quality
cervix squamous epithelium	UBERON:0006922	89.64	silver quality
transverse colon	UBERON:0001157	89.46	gold quality
oocyte	CL:0000023	89.22	gold quality
large intestine	UBERON:0000059	88.85	gold quality
placenta	UBERON:0001987	88.77	gold quality
colon	UBERON:0001155	88.75	gold quality
esophagus mucosa	UBERON:0002469	88.69	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	34.35
E-ANND-3	yes	13.51
E-MTAB-10137	yes	7.71
E-GEOD-110499	no	250.05
E-GEOD-36552	no	109.07

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 7)

• LRRC1 contributes to HCC development, and may be a potential target for therapeutic intervention in this disease. (PMID:23645086)
• Lano/LRRC1-depleted cells secrete increased levels of WNT ligands. (PMID:30344009)
• Common and specific sets of proteins associated to SCRIB and LANO by MS are identified and an extensive landscape of their associated networks and the first comparative analysis of their respective interactomes are provided (PMID:31513346)
• Bone marrow mesenchymal stem cells-derived exosomal microRNA-193a reduces cisplatin resistance of non-small cell lung cancer cells via targeting LRRC1. (PMID:32978367)
• The downstream PPARgamma target LRRC1 participates in early stage adipocytic differentiation. (PMID:36370237)
• LRRC1 knockdown downregulates MACF1 to inhibit the malignant progression of acute myeloid leukemia by inactivating beta-catenin/c-Myc signaling. (PMID:38165568)
• The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3. (PMID:38473980)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc1	ENSDARG00000102684
mus_musculus	Lrrc1	ENSMUSG00000032352
rattus_norvegicus	Lrrc1	ENSRNOG00000005970

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), MFHAS1 (ENSG00000147324), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), LRRC2 (ENSG00000163827), LRRC18 (ENSG00000165383), LRRC28 (ENSG00000168904), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), LRRC8D (ENSG00000171492), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 1 — Q9BTT6 (reviewed: Q9BTT6)

Alternative names: LANO adapter protein, LAP and no PDZ protein

All UniProt accessions (2): Q9BTT6, Q5T0G3

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with DLG1 and DLG4. May form a complex with DLG1 and ERBIN, where interaction between LRRC1 and ERBIN is indirect.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Expressed strongly in testis and placenta, followed by heart, lung, kidney, thyroid, trachea, colon, prostate and pancreas.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BTT6-1	1	yes
Q9BTT6-2	2

RefSeq proteins (1): NP_060684* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050614	Synaptic_Scaffolding_LAP-MAGUK	Family
IPR055414	LRR_R13L4/SHOC2-like	Domain

Pfam: PF13855, PF23598

UniProt features (23 total): repeat 17, splice variant 2, chain 1, coiled-coil region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTT6-F1	85.55	0.76

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 (1): 480

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9696270	RND2 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 181 (showing top): CREL_01, RRAGTTGT_UNKNOWN, FOXO4_01, FOXO1_01, CCATCCA_MIR432, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GTGCCTT_MIR506, chr6p12, BLALOCK_ALZHEIMERS_DISEASE_UP, AACTTT_UNKNOWN, CAIRO_HEPATOBLASTOMA_UP, RYTTCCTG_ETS2_B, NRF2_01, TGCCTTA_MIR124A, CAGCCTC_MIR4855P

GO Biological Process (0):

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

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC1	TINAG	Q9UJW2	589
LRRC1	DLG4	P78352	584
LRRC1	DTNB	O60941	534
LRRC1	ZNF514	Q96K75	527
LRRC1	PTPN3	P26045	446
LRRC1	DEXI	O95424	444
LRRC1	DMD	P11532	407
LRRC1	ZNF654	Q8IZM8	396
LRRC1	SNX7	Q9UNH6	394
LRRC1	KLHL31	Q9H511	387
LRRC1	LGSN	Q5TDP6	359
LRRC1	FDXACB1	Q9BRP7	358
LRRC1	CEBPZ	Q03701	353
LRRC1	PRDX3	P30048	353
LRRC1	SMAP1	Q8IYB5	350

IntAct

109 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
SLX4	ERCC1	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
GXYLT1	CANX	psi-mi:“MI:0914”(association)	0.640
PRSS22	PPM1A	psi-mi:“MI:0914”(association)	0.560
CNPY3	SELENOT	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
STX11	EXOC5	psi-mi:“MI:0914”(association)	0.530
KCNJ6	MB21D2	psi-mi:“MI:0914”(association)	0.530
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
CNPY3	LRIG2	psi-mi:“MI:0914”(association)	0.530
GNLY	YPEL5	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
ZIM2	MDM2	psi-mi:“MI:0914”(association)	0.530
ZNF785	TRIO	psi-mi:“MI:0914”(association)	0.530
SLC25A6	HRAS	psi-mi:“MI:0914”(association)	0.530
LRRC1		psi-mi:“MI:0915”(physical association)	0.400

BioGRID (120): LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS)

ESM2 similar proteins: A6QLV3, A7SFP1, A8XWW4, B0W6M9, B3LWU3, B3P3E8, B4IBI9, B4JTV9, B4LXW1, B4N9T4, B4PU77, B4QVR7, B5DX45, B6CZ61, B9F655, O35125, O88520, Q1L8Y7, Q22875, Q32KP2, Q4R3P6, Q4V8I7, Q53EV4, Q5F4C4, Q5FVI3, Q5GIG6, Q5M8G4, Q5RAV5, Q5RFE9, Q5ZLN0, Q6AYI5, Q6DHL5, Q6GPJ5, Q6INV3, Q6P1C6, Q6UXM1, Q6ZVD8, Q7SXW3, Q7Z4L9, Q80VQ1

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, A5PKA5, F1MCA7, G5ECY0, O14907, O14910, O35274, O35867, O55164, O61967, O62674, O62675, O62676, O88951, O88952, P31016, P57105, P70175, P70587, P78352, P97879, Q0P5E6, Q0P5F3, Q12959, Q13424, Q13425, Q13884, Q14160, Q15599, Q22638, Q28626, Q28C55, Q2KIB6, Q32LE7, Q32LM6, Q3T0C9, Q3UHD6, Q4H4B6, Q5EBL8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHOJ GTPase cycle	5	11.1×	1e-02
Neurotransmitter receptors and postsynaptic signal transmission	7	7.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3387 predictions. Top by Δscore:

Variant	Effect	Δscore
6:53795413:GAG:G	donor_gain	1.0000
6:53795416:G:GG	donor_gain	1.0000
6:53795416:GTA:G	donor_loss	1.0000
6:53795417:T:G	donor_loss	1.0000
6:53842106:TCA:T	acceptor_loss	1.0000
6:53842106:TCAG:T	acceptor_gain	1.0000
6:53842107:CA:C	acceptor_loss	1.0000
6:53842107:CAG:C	acceptor_gain	1.0000
6:53842108:A:AG	acceptor_gain	1.0000
6:53842108:A:C	acceptor_loss	1.0000
6:53842108:AGCAA:A	acceptor_gain	1.0000
6:53842109:G:GA	acceptor_gain	1.0000
6:53842109:GC:G	acceptor_gain	1.0000
6:53842109:GCA:G	acceptor_gain	1.0000
6:53842109:GCAA:G	acceptor_gain	1.0000
6:53842109:GCAAT:G	acceptor_gain	1.0000
6:53842224:AATGG:A	donor_loss	1.0000
6:53842225:ATGG:A	donor_loss	1.0000
6:53842227:GGT:G	donor_loss	1.0000
6:53842228:GTAAG:G	donor_loss	1.0000
6:53842229:T:G	donor_loss	1.0000
6:53882881:TTTTA:T	acceptor_loss	1.0000
6:53882882:TTTA:T	acceptor_loss	1.0000
6:53882883:TTA:T	acceptor_loss	1.0000
6:53882884:TA:T	acceptor_loss	1.0000
6:53882973:GCAA:G	donor_gain	1.0000
6:53882977:G:GG	donor_gain	1.0000
6:53896555:G:GG	donor_gain	1.0000
6:53896891:TGG:T	donor_loss	1.0000
6:53896892:GGTA:G	donor_loss	1.0000

AlphaMissense

3379 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:53795378:T:C	L41P	1.000
6:53842157:T:A	N69K	1.000
6:53842157:T:G	N69K	1.000
6:53842210:T:C	L87P	1.000
6:53896527:G:T	R159I	1.000
6:53896534:T:A	N161K	1.000
6:53896534:T:G	N161K	1.000
6:53896861:T:C	L179P	1.000
6:53897322:T:C	L202P	1.000
6:53795336:T:A	V27D	0.999
6:53795384:T:C	L43P	0.999
6:53795394:C:A	N46K	0.999
6:53795394:C:G	N46K	0.999
6:53842132:T:C	L61S	0.999
6:53842141:T:A	L64H	0.999
6:53842141:T:C	L64P	0.999
6:53842147:T:A	L66H	0.999
6:53842147:T:C	L66P	0.999
6:53842155:A:T	N69Y	0.999
6:53842156:A:T	N69I	0.999
6:53842201:T:A	L84Q	0.999
6:53842201:T:C	L84P	0.999
6:53842225:A:T	N92I	0.999
6:53842226:T:A	N92K	0.999
6:53842226:T:G	N92K	0.999
6:53879035:T:C	L107P	0.999
6:53879044:C:A	A110D	0.999
6:53879060:C:A	N115K	0.999
6:53879060:C:G	N115K	0.999
6:53882928:T:C	L133P	0.999

dbSNP variants (sampled 300 via entrez): RS1000002501 (6:53864635 T>C), RS1000019817 (6:53821453 T>C), RS1000031130 (6:53808867 A>G), RS1000084879 (6:53819870 G>A), RS1000155852 (6:53914667 C>T), RS1000156352 (6:53895994 A>G), RS1000205700 (6:53823890 A>G), RS1000232340 (6:53866216 A>C,G), RS1000253285 (6:53858411 T>C), RS1000254857 (6:53896240 G>C), RS1000257991 (6:53859790 TA>T,TAA), RS1000296084 (6:53888368 A>C), RS1000317376 (6:53852549 G>T), RS1000368064 (6:53852351 C>G), RS1000424808 (6:53894851 C>T)

Disease associations

OMIM: gene MIM:608195 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006979_286	Heel bone mineral density	1.000000e-22
GCST009391_809	Metabolite levels	7.000000e-06
GCST012137_3	Motor coordination	9.000000e-06
GCST90020026_133	Hip index	5.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0010396	sphingomyelin 22:1 measurement
EFO:0010749	motor function measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	5
Progesterone	affects cotreatment, increases expression, decreases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
bisphenol S	affects expression, affects cotreatment, increases expression	2
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Nickel	decreases expression	1
Smoke	decreases expression	1
Sodium Chloride	increases expression, affects cotreatment, affects localization, decreases expression	1
Dronabinol	decreases expression	1

Clinical trials (associated diseases)

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