LRRC3B

Summary

LRRC3B (leucine rich repeat containing 3B, HGNC:28105) is a protein-coding gene on chromosome 3p24.1, encoding Leucine-rich repeat-containing protein 3B (Q96PB8).

The protein encoded by this gene is a tumor suppressor, with lowered expression levels found in gastric, renal, colorectal, lung, and breast cancer tissues. The promoter of this gene is frequently hypermethylated in these cancer tissues, although the hypermethylation does not appear to be the cause of the reduced expression of this gene. Several transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 116135 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_052953

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28105
Approved symbol	LRRC3B
Name	leucine rich repeat containing 3B
Location	3p24.1
Locus type	gene with protein product
Status	Approved
Aliases	LRP15
Ensembl gene	ENSG00000179796
Ensembl biotype	protein_coding
OMIM	618996
Entrez	116135

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000396641, ENST00000414619, ENST00000417744, ENST00000432040, ENST00000456208, ENST00000469437, ENST00000648296, ENST00000891723, ENST00000936107

RefSeq mRNA: 8 — MANE Select: NM_052953 NM_001317808, NM_001317809, NM_001317810, NM_001317811, NM_001395645, NM_001395646, NM_001395647, NM_052953

CCDS: CCDS2644

Canonical transcript exons

ENST00000396641 — 2 exons

Exon	Start	End
ENSE00001525802	26709513	26710776
ENSE00003978174	26622772	26623237

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 99.12.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2590 / max 85.5196, expressed in 235 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35768	0.6845	194
35765	0.2686	127
35767	0.1749	96
35766	0.1214	69
35769	0.0096	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.12	gold quality
ganglionic eminence	UBERON:0004023	98.12	gold quality
cortical plate	UBERON:0005343	91.96	gold quality
secondary oocyte	CL:0000655	90.18	gold quality
cerebellum	UBERON:0002037	87.93	gold quality
cerebellar cortex	UBERON:0002129	87.84	gold quality
cerebellar hemisphere	UBERON:0002245	87.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.48	gold quality
amygdala	UBERON:0001876	87.23	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.10	gold quality
substantia nigra pars compacta	UBERON:0001965	86.50	gold quality
putamen	UBERON:0001874	86.42	gold quality
nucleus accumbens	UBERON:0001882	85.82	gold quality
caudate nucleus	UBERON:0001873	85.69	gold quality
oocyte	CL:0000023	85.51	gold quality
endothelial cell	CL:0000115	84.50	gold quality
temporal lobe	UBERON:0001871	84.43	gold quality
anterior cingulate cortex	UBERON:0009835	84.33	gold quality
lateral nuclear group of thalamus	UBERON:0002736	83.13	gold quality
right frontal lobe	UBERON:0002810	82.81	gold quality
cerebellar vermis	UBERON:0004720	82.61	gold quality
substantia nigra	UBERON:0002038	82.58	gold quality
prefrontal cortex	UBERON:0000451	82.34	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.30	gold quality
neocortex	UBERON:0001950	82.11	gold quality
cerebral cortex	UBERON:0000956	82.02	gold quality
Ammon’s horn	UBERON:0001954	81.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.50	gold quality
midbrain	UBERON:0001891	81.45	gold quality
frontal cortex	UBERON:0001870	81.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	7.72
E-ANND-3	yes	5.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXN1

miRNA regulators (miRDB)

45 targeting LRRC3B, 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-126-5P	100.00	72.71	3180
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4738-3P	98.98	67.98	1846

Literature-anchored findings (GeneRIF, showing 9)

• The expression of LRP15 is controlled by methylation in its promoter in HeLa cells, and LRP15 confers resistance to ultraviolet rays damage and accelerates the DNA repair rate. (PMID:18377727)
• suggest that LRRC3B is a putative tumor suppressor gene that is silenced in gastric cancers by epigenetic mechanisms and that LRRC3B silencing in cancer may play an important role in tumor escape from immune surveillance (PMID:18757430)
• LRRC3B may be a novel methylation-sensitive tumor suppressor gene in CRC. LRRC3B methylation has significant tumor specificity and may be a biomarker of CRC. (PMID:18815942)
• The LRRC3B gene promoter was methylated in 43% of clear cell renal carcinoma samples. (PMID:22101383)
• Data suggest that LRRC3B gene could be involved in the process of carcinogenesis as a tumor suppressor gene. (PMID:22321817)
• LRRC3B gene expression and promoter hypermethylation in breast carcinomas (PMID:24839112)
• LRRC3B may serve as an important tumor suppressor in non-small-cell lung cancer (PMID:26276358)
• The expression of LRRC3B is downregulated in non-small cell lung cancer compared with normal epithelial cells. (PMID:27118644)
• LRRC3B and its promoter hypomethylation status predicts response to anti-PD-1 based immunotherapy. (PMID:36798137)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc3b	ENSDARG00000063215
mus_musculus	Lrrc3b	ENSMUSG00000045201
rattus_norvegicus	Lrrc3b	ENSRNOG00000005857

Paralogs (22): IGFALS (ENSG00000099769), TLR8 (ENSG00000101916), LRRC17 (ENSG00000128606), RXFP2 (ENSG00000133105), CD180 (ENSG00000134061), TLR4 (ENSG00000136869), TLR2 (ENSG00000137462), LRRC32 (ENSG00000137507), LRRC3 (ENSG00000160233), LRRC53 (ENSG00000162621), TLR3 (ENSG00000164342), VASN (ENSG00000168140), RXFP1 (ENSG00000171509), NRROS (ENSG00000174004), TLR10 (ENSG00000174123), TLR1 (ENSG00000174125), TLR6 (ENSG00000174130), TSKU (ENSG00000182704), TLR5 (ENSG00000187554), TLR7 (ENSG00000196664), LRIT2 (ENSG00000204033), LRRC3C (ENSG00000204913)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 3B — Q96PB8 (reviewed: Q96PB8)

Alternative names: Leucine-rich repeat protein 15

All UniProt accessions (3): C9J6A1, C9JMC7, Q96PB8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the LRRC3 family.

RefSeq proteins (8): NP_001304737, NP_001304738, NP_001304739, NP_001304740, NP_001382574, NP_001382575, NP_001382576, NP_443185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF00560, PF01462, PF13855

UniProt features (11 total): repeat 3, domain 2, glycosylation site 2, signal peptide 1, chain 1, strand 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5EMA	X-RAY DIFFRACTION	1.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PB8-F1	86.05	0.55

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 (2): 47, 94

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): RNGTGGGC_UNKNOWN, TAATAAT_MIR126, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, AACTTT_UNKNOWN, CTTTGTA_MIR524, AP1FJ_Q2, HATADA_METHYLATED_IN_LUNG_CANCER_UP, MEISSNER_NPC_HCP_WITH_H3K4ME2, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, chr3p24, MIR520D_5P, MIR524_5P, MIR126_5P, GSE10239_NAIVE_VS_KLRG1INT_EFF_CD8_TCELL_DN

GO Biological Process (0):

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC3B	TOPAZ1	Q8N9V7	479
LRRC3B	CGGBP1	Q9UFW8	476
LRRC3B	A0A3B3IT14	A0A3B3IT14	475
LRRC3B	FOXP1	Q9H334	475
LRRC3B	CTDSPL	O15194	448
LRRC3B	NKIRAS1	Q9NYS0	447
LRRC3B	PLEKHD1	A6NEE1	446
LRRC3B	GASK1B	Q6UWH4	445
LRRC3B	IRAG1	Q9Y6F6	436
LRRC3B	STOX1	Q6ZVD7	431
LRRC3B	HMX2	A2RU54	418
LRRC3B	LRRC58	Q96CX6	417
LRRC3B	FGD5	Q6ZNL6	395
LRRC3B	NOL4	O94818	384
LRRC3B	LRRC20	Q8TCA0	382

IntAct

20 interactions, top by confidence:

A	B	Type	Score
TMEM220	LRRC3B	psi-mi:“MI:0915”(physical association)	0.560
MS4A13	LRRC3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM60	LRRC3B	psi-mi:“MI:0915”(physical association)	0.560
CD37	LRRC3B	psi-mi:“MI:0915”(physical association)	0.560
YIPF6	LRRC3B	psi-mi:“MI:0915”(physical association)	0.560
LRRC3B	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
EMP1	LRRC3B	psi-mi:“MI:0915”(physical association)	0.560
LRRC3B	PKLR	psi-mi:“MI:0914”(association)	0.350
YIPF6	LRRC3B	psi-mi:“MI:0915”(physical association)	0.000
EMP1	LRRC3B	psi-mi:“MI:0915”(physical association)	0.000
LRRC3B	EMP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): LRRC3B (Two-hybrid), LRRC3B (Two-hybrid), LRRC3B (Two-hybrid), YIPF6 (Two-hybrid), TMEM220 (Two-hybrid), MS4A13 (Two-hybrid), C1orf27 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), UBE2S (Affinity Capture-MS), DNPEP (Affinity Capture-MS), IMPACT (Affinity Capture-MS), PKLR (Affinity Capture-MS), LRRC3B (Positive Genetic), LRRC3B (Two-hybrid)

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: A3KNN3, A4IIW9, A6H789, A6H793, A6NJW4, A8WHP9, E9Q7T7, O46379, O75093, O75094, O88280, O94769, P21793, P24014, P51884, P51885, P51886, P59034, P59035, P83503, Q05443, Q3MHH9, Q5FW85, Q5M7S9, Q65YW8, Q6EMK4, Q6NUI6, Q6R5N8, Q8R5M3, Q8VCH9, Q96PB8, Q9BY71, Q9GKQ6, Q9GZU5, Q9TTE2, Q9WVB4, Q9WVC1, Q9Z0L0, E7FE13, F1MLX5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

890 predictions. Top by Δscore:

Variant	Effect	Δscore
3:26643685:GC:G	donor_gain	0.9900
3:26643686:C:G	donor_gain	0.9900
3:26709507:CTTTA:C	acceptor_loss	0.9900
3:26709509:TTAG:T	acceptor_loss	0.9900
3:26709511:A:AC	acceptor_loss	0.9900
3:26709511:A:AG	acceptor_gain	0.9900
3:26709512:G:A	acceptor_loss	0.9900
3:26709512:G:GG	acceptor_gain	0.9900
3:26623234:CAAG:C	donor_loss	0.9800
3:26623235:AAG:A	donor_loss	0.9800
3:26623238:GT:G	donor_loss	0.9800
3:26623239:T:G	donor_loss	0.9800
3:26697041:ACTT:A	acceptor_gain	0.9800
3:26709512:GGT:G	acceptor_gain	0.9800
3:26625171:G:A	acceptor_gain	0.9600
3:26643686:C:CG	donor_gain	0.9400
3:26709511:AG:A	acceptor_gain	0.9400
3:26709512:GG:G	acceptor_gain	0.9400
3:26623238:G:GG	donor_gain	0.9300
3:26701247:G:GG	donor_gain	0.9300
3:26709511:AGGT:A	acceptor_gain	0.9200
3:26709512:GGTG:G	acceptor_gain	0.9200
3:26709512:GGTGC:G	acceptor_gain	0.9200
3:26643684:GGC:G	donor_gain	0.9100
3:26625170:C:CA	acceptor_gain	0.8900
3:26632098:G:GT	donor_gain	0.8900
3:26636483:A:G	donor_gain	0.8800
3:26697042:CTTA:C	acceptor_gain	0.8800
3:26624024:GGATT:G	donor_gain	0.8600
3:26625245:G:A	acceptor_gain	0.8600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046454 (3:26640538 C>T), RS1000064399 (3:26689043 G>A), RS1000081855 (3:26698975 A>G), RS1000083274 (3:26709445 A>G), RS1000117309 (3:26646573 C>T), RS1000156058 (3:26652581 C>T), RS1000215605 (3:26662027 T>C), RS1000292947 (3:26652767 A>C,G,T), RS1000378663 (3:26639834 T>C), RS1000432640 (3:26639592 C>G,T), RS1000471156 (3:26646301 A>G), RS1000508067 (3:26624117 C>T), RS1000537804 (3:26657528 A>T), RS1000585133 (3:26652887 T>G), RS1000604644 (3:26665045 C>G)

Disease associations

OMIM: gene MIM:618996 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008155_15	Waist-hip ratio	8.000000e-06
GCST009310_7	Sensorimotor dexterity	3.000000e-06
GCST012419_4	Longevity (100 years and older)	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0008354	cognitive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	7
trichostatin A	decreases expression, affects cotreatment, affects expression, affects methylation	5
Decitabine	affects expression, affects methylation, affects cotreatment, decreases methylation, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenite	increases expression	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, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	increases expression	1
Lead	affects expression	1
Pesticides	affects methylation	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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