LRRC2

Summary

LRRC2 (leucine rich repeat containing 2, HGNC:14676) is a protein-coding gene on chromosome 3p21.31, encoding Leucine-rich repeat-containing protein 2 (Q9BYS8).

This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2.

Source: NCBI Gene 79442 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_024512

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14676
Approved symbol	LRRC2
Name	leucine rich repeat containing 2
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163827
Ensembl biotype	protein_coding
OMIM	607180
Entrez	79442

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000296144, ENST00000395905, ENST00000469912, ENST00000496388, ENST00000682605, ENST00000872818, ENST00000872819, ENST00000872820, ENST00000872821, ENST00000938206, ENST00000938207, ENST00000951503, ENST00000951504, ENST00000951505, ENST00000951506, ENST00000951507, ENST00000951508, ENST00000951509

RefSeq mRNA: 1 — MANE Select: NM_024512 NM_024512

CCDS: CCDS2741

Canonical transcript exons

ENST00000395905 — 9 exons

Exon	Start	End
ENSE00001078640	46527426	46527581
ENSE00001078641	46532773	46532909
ENSE00001078642	46521522	46521658
ENSE00001078643	46551467	46551610
ENSE00001078644	46545046	46545253
ENSE00001078645	46539045	46539201
ENSE00001078646	46529905	46530050
ENSE00001523226	46515385	46519063
ENSE00001946152	46566177	46566302

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 98.96.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1800 / max 215.8871, expressed in 584 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41993	1.3048	412
41995	0.3492	184
41992	0.2629	91
202744	0.1214	38
41996	0.0657	23
41994	0.0557	20
41991	0.0205	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.96	gold quality
biceps brachii	UBERON:0001507	98.73	gold quality
vastus lateralis	UBERON:0001379	98.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.98	gold quality
skeletal muscle tissue	UBERON:0001134	97.57	gold quality
gluteal muscle	UBERON:0002000	97.54	gold quality
diaphragm	UBERON:0001103	97.41	gold quality
quadriceps femoris	UBERON:0001377	97.38	gold quality
heart right ventricle	UBERON:0002080	97.35	gold quality
body of tongue	UBERON:0011876	96.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.14	gold quality
triceps brachii	UBERON:0001509	96.13	gold quality
gastrocnemius	UBERON:0001388	95.96	gold quality
deltoid	UBERON:0001476	95.88	gold quality
muscle organ	UBERON:0001630	95.61	gold quality
left ventricle myocardium	UBERON:0006566	95.27	gold quality
tibialis anterior	UBERON:0001385	95.22	gold quality
muscle of leg	UBERON:0001383	94.78	gold quality
muscle tissue	UBERON:0002385	93.12	gold quality
cardiac ventricle	UBERON:0002082	92.60	gold quality
heart left ventricle	UBERON:0002084	92.48	gold quality
apex of heart	UBERON:0002098	91.23	gold quality
renal glomerulus	UBERON:0000074	89.71	gold quality
metanephric glomerulus	UBERON:0004736	89.17	gold quality
myocardium	UBERON:0002349	85.91	gold quality
tongue	UBERON:0001723	85.01	gold quality
heart	UBERON:0000948	84.15	gold quality
thyroid gland	UBERON:0002046	82.32	gold quality
right lobe of thyroid gland	UBERON:0001119	81.70	gold quality
left lobe of thyroid gland	UBERON:0001120	81.40	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	26.00
E-ANND-3	yes	4.85
E-GEOD-124858	no	91.25
E-ENAD-27	no	4.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

141 targeting LRRC2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-302E	99.96	70.74	2669

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc2	ENSMUSG00000032495
rattus_norvegicus	Lrrc2	ENSRNOG00000030688

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), LRRC1 (ENSG00000137269), MFHAS1 (ENSG00000147324), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), 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 2 — Q9BYS8 (reviewed: Q9BYS8)

All UniProt accessions (1): Q9BYS8

RefSeq proteins (1): NP_078788* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR025875	Leu-rich_rpt_4	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050216	LRR_domain-containing	Family

Pfam: PF12799, PF13855

UniProt features (14 total): repeat 9, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYS8-F1	77.89	0.44

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): RODWELL_AGING_KIDNEY_NO_BLOOD_DN, TGANTCA_AP1_C, AACTTT_UNKNOWN, BRACHAT_RESPONSE_TO_METHOTREXATE_UP, MEF2_Q6_01, BRACHAT_RESPONSE_TO_CAMPTOTHECIN_UP, P53_DECAMER_Q2, NFE2_01, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, TTCNRGNNNNTTC_HSF_Q6, TGGAAA_NFAT_Q4_01, ALONSO_METASTASIS_DN, TGATTTRY_GFI1_01, MIKKELSEN_ES_ICP_WITH_H3K4ME3, AP1_Q6_01

GO Biological Process (1): intracellular signal transduction (GO:0035556)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	1
signal transduction	1
binding	1

Protein interactions and networks

STRING

1068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC2	GPALPP1	Q8IXQ4	537
LRRC2	CCDC82	Q8N4S0	513
LRRC2	ZNF770	Q6IQ21	507
LRRC2	RTP3	Q9BQQ7	480
LRRC2	CISH	Q9NSE2	427
LRRC2	DOCK3	Q8IZD9	410
LRRC2	ALS2CL	Q60I27	402
LRRC2	ANTXR2	P58335	400
LRRC2	RCBTB2	O95199	375
LRRC2	TMEM70	Q9BUB7	369
LRRC2	ASB11	Q8WXH4	368
LRRC2	HMBOX1	Q6NT76	367
LRRC2	LRRC14B	A6NHZ5	361
LRRC2	EEF2K	O00418	353
LRRC2	IGFALS	P35858	353

IntAct

4 interactions, top by confidence:

A	B	Type	Score
	LRRC2	psi-mi:“MI:0915”(physical association)	0.400
CETN2	DVL1	psi-mi:“MI:2364”(proximity)	0.270
LRRC2	TP53RK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): LRRC2 (Proximity Label-MS), LRRC2 (Two-hybrid), LRRC2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A4D1F6, A4IIK1, A6H6A4, A6NIV6, A6NM36, C0STK7, D3ZXS4, F1R6I3, F6R2G2, P14605, Q09562, Q32KX5, Q38SD2, Q3TX51, Q3UHC2, Q3UV48, Q3ZC49, Q4R6F0, Q54AX5, Q58A48, Q5G5E0, Q62192, Q65YW8, Q65Z91, Q66HD6, Q6AXL3, Q6GLE8, Q6GM71, Q6R5N8, Q6ZNQ3, Q7Z2Q7, Q86X40, Q8BGI7, Q8C0R9, Q8N456, Q8VDB8, Q96DD0, Q99467, Q99MB1, Q9BYS8

Diamond homologs: D3ZXS4, F1R6I3, Q3ZC49, Q8BGI7, Q8VDB8, Q96DD0, Q9BYS8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2347 predictions. Top by Δscore:

Variant	Effect	Δscore
3:46518974:G:C	donor_gain	1.0000
3:46521517:CCCA:C	donor_loss	1.0000
3:46521519:CA:C	donor_loss	1.0000
3:46521521:C:G	donor_loss	1.0000
3:46521521:CCT:C	donor_gain	1.0000
3:46521654:CAAAT:C	acceptor_gain	1.0000
3:46521659:C:CC	acceptor_gain	1.0000
3:46527424:A:AC	donor_gain	1.0000
3:46527425:C:CC	donor_gain	1.0000
3:46530046:CTTAA:C	acceptor_gain	1.0000
3:46532765:T:C	donor_gain	1.0000
3:46532768:CTTA:C	donor_loss	1.0000
3:46532769:TTA:T	donor_loss	1.0000
3:46532770:TAC:T	donor_loss	1.0000
3:46532771:A:AC	donor_gain	1.0000
3:46532772:C:CA	donor_gain	1.0000
3:46532772:CT:C	donor_gain	1.0000
3:46532772:CTT:C	donor_gain	1.0000
3:46532774:T:TA	donor_gain	1.0000
3:46532906:CAAC:C	acceptor_gain	1.0000
3:46532910:C:CC	acceptor_gain	1.0000
3:46532911:T:C	acceptor_loss	1.0000
3:46532915:A:T	acceptor_gain	1.0000
3:46532917:C:CT	acceptor_gain	1.0000
3:46532918:A:T	acceptor_gain	1.0000
3:46539199:CTC:C	acceptor_gain	1.0000
3:46539201:CCTA:C	acceptor_loss	1.0000
3:46539202:C:CC	acceptor_gain	1.0000
3:46539202:C:G	acceptor_loss	1.0000
3:46539203:T:G	acceptor_loss	1.0000

AlphaMissense

2478 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:46539159:A:G	W126R	0.993
3:46539159:A:T	W126R	0.993
3:46532885:A:G	L172P	0.992
3:46527545:G:C	N270K	0.984
3:46527545:G:T	N270K	0.984
3:46532816:A:G	L195P	0.984
3:46529962:A:C	L239W	0.982
3:46529923:A:C	L252R	0.981
3:46532869:G:C	N177K	0.980
3:46532869:G:T	N177K	0.980
3:46539083:A:G	L151P	0.979
3:46551543:A:G	W17R	0.979
3:46551543:A:T	W17R	0.979
3:46529923:A:T	L252Q	0.978
3:46532800:A:C	N200K	0.978
3:46532800:A:T	N200K	0.978
3:46529953:A:G	L242S	0.977
3:46529989:G:C	P230R	0.977
3:46532783:A:C	L206R	0.976
3:46532885:A:T	L172H	0.976
3:46532894:A:G	L169P	0.976
3:46539089:A:G	L149P	0.974
3:46527547:T:A	N270Y	0.973
3:46529943:G:C	S245R	0.972
3:46529943:G:T	S245R	0.972
3:46529945:T:G	S245R	0.972
3:46529992:A:T	V229D	0.972
3:46530049:A:G	L210S	0.972
3:46529937:A:C	N247K	0.971
3:46529937:A:T	N247K	0.971

dbSNP variants (sampled 300 via entrez): RS1000011222 (3:46537871 G>A), RS1000011891 (3:46544428 G>A), RS1000023684 (3:46522807 AC>A), RS1000165512 (3:46518663 C>G), RS1000210470 (3:46562375 C>G), RS1000216445 (3:46537124 G>T), RS1000238022 (3:46529831 T>C,G), RS1000249839 (3:46549997 T>G), RS1000290037 (3:46536761 C>T), RS1000330251 (3:46515860 A>G), RS1000357004 (3:46555860 A>C), RS1000473731 (3:46543533 G>A), RS1000498215 (3:46528181 T>C,G), RS1000567260 (3:46530143 G>A), RS1000610340 (3:46539547 G>A)

Disease associations

OMIM: gene MIM:607180 | 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
GCST009391_386	Metabolite levels	5.000000e-06
GCST009391_924	Metabolite levels	3.000000e-06
GCST010002_422	Refractive error	4.000000e-14
GCST010767_5	Coronary atherosclerosis (time to event)	5.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010437	triacylglycerol 58:10 measurement
EFO:0010443	triacylglycerol 58:9 measurement
EFO:0004918	age at diagnosis
EFO:0007938	coronary atherosclerosis 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
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression, decreases methylation	2
Silicon Dioxide	increases expression, decreases expression, increases methylation	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	decreases expression, increases methylation	2
bisphenol A	affects cotreatment, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aldrin	affects cotreatment, decreases expression	1
Hexachlorocyclohexane	affects cotreatment, decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Dichlorodiphenyldichloroethane	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	affects cotreatment, decreases expression	1
DDT	decreases expression, affects cotreatment	1
Dieldrin	decreases expression, affects cotreatment	1
Endrin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Plant Oils	increases expression	1
Smoke	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	increases expression	1
Asbestos, Serpentine	increases expression	1
Okadaic Acid	decreases expression	1
Simvastatin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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