LRRC3

Summary

LRRC3 (leucine rich repeat containing 3, HGNC:14965) is a protein-coding gene on chromosome 21q22.3, encoding Leucine-rich repeat-containing protein 3 (Q9BY71).

Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 81543 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_030891

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14965
Approved symbol	LRRC3
Name	leucine rich repeat containing 3
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434C128
Ensembl gene	ENSG00000160233
Ensembl biotype	protein_coding
OMIM	617620
Entrez	81543

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000291592, ENST00000885220, ENST00000885221

RefSeq mRNA: 1 — MANE Select: NM_030891 NM_030891

CCDS: CCDS13711

Canonical transcript exons

ENST00000291592 — 2 exons

Exon	Start	End
ENSE00001050784	44456498	44462196
ENSE00001838176	44455510	44455655

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 81.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3240 / max 46.5520, expressed in 1208 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189484	3.3240	1208

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	81.62	gold quality
cortical plate	UBERON:0005343	80.91	gold quality
liver	UBERON:0002107	77.21	gold quality
ganglionic eminence	UBERON:0004023	76.68	gold quality
secondary oocyte	CL:0000655	75.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.76	gold quality
ventricular zone	UBERON:0003053	74.17	gold quality
oocyte	CL:0000023	71.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.86	silver quality
vena cava	UBERON:0004087	71.69	gold quality
sperm	CL:0000019	71.63	gold quality
descending thoracic aorta	UBERON:0002345	71.18	gold quality
thoracic aorta	UBERON:0001515	70.85	gold quality
ascending aorta	UBERON:0001496	70.84	gold quality
thymus	UBERON:0002370	69.99	gold quality
cerebellar vermis	UBERON:0004720	69.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	69.33	gold quality
parotid gland	UBERON:0001831	68.87	gold quality
mucosa of stomach	UBERON:0001199	68.84	gold quality
apex of heart	UBERON:0002098	68.79	gold quality
pharyngeal mucosa	UBERON:0000355	68.66	gold quality
inferior vagus X ganglion	UBERON:0005363	68.55	gold quality
fundus of stomach	UBERON:0001160	68.50	gold quality
cardia of stomach	UBERON:0001162	68.38	gold quality
left ovary	UBERON:0002119	68.27	gold quality
saphenous vein	UBERON:0007318	68.21	gold quality
nipple	UBERON:0002030	68.18	gold quality
substantia nigra pars compacta	UBERON:0001965	68.15	gold quality
pericardium	UBERON:0002407	67.91	gold quality
tongue	UBERON:0001723	67.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting LRRC3, 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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362

Literature-anchored findings (GeneRIF, showing 1)

• The C21orf30 distal promoter contains an activating cis-regulatory element that is responsive to serum depletion according to promoter reporter assays in HEK 293 cells. (PMID:20494980)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc3	ENSDARG00000078415
mus_musculus	Lrrc3	ENSMUSG00000051652
rattus_norvegicus	Lrrc3	ENSRNOG00000001217

Paralogs (22): IGFALS (ENSG00000099769), TLR8 (ENSG00000101916), LRRC17 (ENSG00000128606), RXFP2 (ENSG00000133105), CD180 (ENSG00000134061), TLR4 (ENSG00000136869), TLR2 (ENSG00000137462), LRRC32 (ENSG00000137507), LRRC53 (ENSG00000162621), TLR3 (ENSG00000164342), VASN (ENSG00000168140), RXFP1 (ENSG00000171509), NRROS (ENSG00000174004), TLR10 (ENSG00000174123), TLR1 (ENSG00000174125), TLR6 (ENSG00000174130), LRRC3B (ENSG00000179796), TSKU (ENSG00000182704), TLR5 (ENSG00000187554), TLR7 (ENSG00000196664), LRIT2 (ENSG00000204033), LRRC3C (ENSG00000204913)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 3 — Q9BY71 (reviewed: Q9BY71)

All UniProt accessions (1): Q9BY71

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Widely expressed; detected in testis, lung, small intestine, breast, brain, heart, bone marrow, placenta, colon, fetal brain, liver, fetal liver, thymus, salivary gland, spinal cord, spleen, trachea and adrenal gland.

Similarity. Belongs to the LRRC3 family.

RefSeq proteins (1): NP_112153* (*=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
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF00560, PF01462, PF13855

UniProt features (8 total): repeat 4, signal peptide 1, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY71-F1	83.43	0.51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, chr21q22, SAFFORD_T_LYMPHOCYTE_ANERGY, MODULE_325, MEISSNER_NPC_HCP_WITH_H3K4ME2, FIGUEROA_AML_METHYLATION_CLUSTER_1_DN, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_C, CERIBELLI_GENES_INACTIVE_AND_BOUND_BY_NFY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GSE5503_MLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_UP, SOX3_TARGET_GENES, ZNF22_TARGET_GENES, MIR96_5P, MIR1827, MIR1271_5P

GO Biological Process (0):

GO Molecular Function (1): 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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC3	CASP1	P29466	855
LRRC3	PYCARD	Q9ULZ3	728
LRRC3	NLRP3	Q96P20	689
LRRC3	DPY19L4	Q7Z388	493
LRRC3	TMEM9B	Q9NQ34	473
LRRC3	CCNQ	Q8N1B3	462
LRRC3	NOC4L	Q9BVI4	460
LRRC3	VWA7	Q9Y334	458
LRRC3	GK5	Q6ZS86	449
LRRC3	SLC45A1	Q9Y2W3	446
LRRC3	HABP4	Q5JVS0	437
LRRC3	KCNK17	Q96T54	437
LRRC3	C1QL2	Q7Z5L3	433
LRRC3	COQ5	Q5HYK3	427
LRRC3	TRMT13	Q9NUP7	416

IntAct

29 interactions, top by confidence:

A	B	Type	Score
SCNN1D	ABHD16A	psi-mi:“MI:0914”(association)	0.530
CHST6	CANX	psi-mi:“MI:0914”(association)	0.530
ADAM21	PLXNA2	psi-mi:“MI:0914”(association)	0.530
LRRC3	NCK1	psi-mi:“MI:0915”(physical association)	0.400
LRRC3	SEPTIN9	psi-mi:“MI:0915”(physical association)	0.400
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
ADAM21	PLXNB2	psi-mi:“MI:0914”(association)	0.350
NCEH1	C1QL1	psi-mi:“MI:0914”(association)	0.350
ADAM2	ADAMTS2	psi-mi:“MI:0914”(association)	0.350
GALNT13	GALNT1	psi-mi:“MI:0914”(association)	0.350
ADAM17	SDK2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
TMEM106A	RTL8C	psi-mi:“MI:0914”(association)	0.350
TAS1R2	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
TLR9	ABCD4	psi-mi:“MI:0914”(association)	0.350
KLRC3	RNF13	psi-mi:“MI:0914”(association)	0.350
TAS1R3	SUN1	psi-mi:“MI:0914”(association)	0.350
CHST6	HSPA5	psi-mi:“MI:0914”(association)	0.350
LRRC52	CANX	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), SEPT9 (Proximity Label-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A2ARI4, A2VDH3, A6H793, D4A6D8, E9Q7T7, F1MLX5, F1MT22, O75325, P59034, P59035, Q13641, Q149C3, Q3URE9, Q3UVD5, Q3UY51, Q4KLL3, Q4R8Y9, Q50LG9, Q5M8M9, Q5PQV5, Q5R6B1, Q5RDJ4, Q5VT99, Q6GQU6, Q6UY18, Q6ZSA7, Q7M6Z0, Q7TQ62, Q80WD1, Q86UE6, Q86UN2, Q86UN3, Q86WK6, Q8BHA1, Q8K0S5, Q8K377, Q8N7C0, Q91ZV8, Q96FE5

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

431 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44455651:CGCAG:C	donor_loss	0.9900
21:44455654:AGGT:A	donor_loss	0.9900
21:44455656:GTAAA:G	donor_loss	0.9900
21:44455657:T:G	donor_loss	0.9900
21:44457364:G:GT	donor_gain	0.9800
21:44455656:G:GG	donor_gain	0.9500
21:44457355:G:GT	donor_gain	0.9500
21:44457335:G:GT	donor_gain	0.9400
21:44455652:GCAG:G	donor_gain	0.9300
21:44457652:A:T	donor_gain	0.9300
21:44457651:G:GT	donor_gain	0.9100
21:44457176:G:GT	donor_gain	0.8800
21:44455968:G:T	donor_gain	0.8700
21:44456795:A:AG	acceptor_gain	0.8600
21:44456796:G:GG	acceptor_gain	0.8600
21:44457395:G:GT	donor_gain	0.8500
21:44457765:GAC:G	donor_gain	0.8000
21:44457772:G:GT	donor_gain	0.8000
21:44455653:C:T	donor_gain	0.7900
21:44460014:G:GT	donor_gain	0.7900
21:44457465:G:GG	donor_gain	0.7700
21:44457991:C:G	donor_gain	0.7400
21:44460217:T:A	acceptor_gain	0.7400
21:44456796:GCTT:G	acceptor_gain	0.7300
21:44457471:G:GA	donor_gain	0.7300
21:44457346:G:GT	donor_gain	0.7200
21:44457464:A:AG	donor_gain	0.7200
21:44460221:G:A	acceptor_gain	0.7000
21:44456496:A:AG	acceptor_gain	0.6900
21:44456497:G:GG	acceptor_gain	0.6900

AlphaMissense

1656 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44457012:A:T	N123I	0.999
21:44457011:A:T	N123Y	0.998
21:44457013:C:A	N123K	0.998
21:44457013:C:G	N123K	0.998
21:44456865:A:T	N74I	0.997
21:44456871:T:C	I76T	0.997
21:44456895:T:G	F84C	0.997
21:44456937:A:T	N98I	0.997
21:44457284:T:A	W214R	0.997
21:44457284:T:C	W214R	0.997
21:44457003:T:C	L120P	0.996
21:44457079:C:A	N145K	0.996
21:44457079:C:G	N145K	0.996
21:44456856:T:A	L71H	0.995
21:44456913:T:A	L90H	0.995
21:44456922:T:C	L93P	0.995
21:44456928:T:C	L95P	0.995
21:44456936:A:T	N98Y	0.995
21:44456938:C:A	N98K	0.995
21:44456938:C:G	N98K	0.995
21:44456967:T:G	F108C	0.995
21:44457158:T:A	C172S	0.995
21:44457159:G:C	C172S	0.995
21:44456850:T:C	L69P	0.994
21:44456856:T:C	L71P	0.994
21:44456895:T:C	F84S	0.994
21:44457018:T:C	I125T	0.994
21:44457077:A:T	N145Y	0.994
21:44456866:C:A	N74K	0.993
21:44456866:C:G	N74K	0.993

dbSNP variants (sampled 300 via entrez): RS1000070925 (21:44462429 A>G), RS1000374229 (21:44457738 C>G), RS1000620894 (21:44459812 G>C), RS1000856503 (21:44461696 G>A), RS1001080226 (21:44461419 G>A), RS1001205487 (21:44462013 G>A), RS1001258395 (21:44456733 G>A), RS1001419279 (21:44458354 G>A), RS1002287224 (21:44458621 A>G), RS1002828057 (21:44457312 T>C), RS1002895850 (21:44455697 A>C), RS1002982122 (21:44461440 C>T), RS1002982756 (21:44453799 G>A), RS1004692534 (21:44455498 C>T), RS1004889397 (21:44457444 G>A,T)

Disease associations

OMIM: gene MIM:617620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004793_1	Amyotrophic lateral sclerosis in C9orf72 mutation negative individuals	2.000000e-07
GCST007354_28	Intracranial aneurysm	4.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silver	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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