LRRC19

Summary

LRRC19 (leucine rich repeat containing 19, HGNC:23379) is a protein-coding gene on chromosome 9p21.2, encoding Leucine-rich repeat-containing protein 19 (Q9H756). Pathogen-recognition receptor which mediates the activation of TRAF2- and TRAF6 NF-kappa-B signaling pathways and induces the expression of pro-inflammatory cytokines.

Predicted to enable signaling receptor activity. Acts upstream of or within positive regulation of non-canonical NF-kappaB signal transduction. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 64922 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_022901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23379
Approved symbol	LRRC19
Name	leucine rich repeat containing 19
Location	9p21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21302
Ensembl gene	ENSG00000184434
Ensembl biotype	protein_coding
OMIM	619068
Entrez	64922

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000380055, ENST00000482770, ENST00000903358, ENST00000903359, ENST00000951626

RefSeq mRNA: 1 — MANE Select: NM_022901 NM_022901

CCDS: CCDS6518

Canonical transcript exons

ENST00000380055 — 5 exons

Exon	Start	End
ENSE00001304899	26997728	26998241
ENSE00001306241	27005592	27005672
ENSE00001324201	26996311	26996499
ENSE00001483592	26993136	26995849
ENSE00001483594	26999614	26999703

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 95.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3546 / max 159.4411, expressed in 22 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100326	0.2445	20
100325	0.0813	11
100327	0.0289	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	95.85	gold quality
colonic mucosa	UBERON:0000317	95.50	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.16	gold quality
rectum	UBERON:0001052	93.45	gold quality
mucosa of transverse colon	UBERON:0004991	91.67	gold quality
nephron tubule	UBERON:0001231	88.93	gold quality
duodenum	UBERON:0002114	88.61	gold quality
ileal mucosa	UBERON:0000331	86.08	gold quality
kidney epithelium	UBERON:0004819	83.21	gold quality
adult mammalian kidney	UBERON:0000082	82.57	gold quality
kidney	UBERON:0002113	81.23	gold quality
renal glomerulus	UBERON:0000074	80.92	gold quality
metanephric glomerulus	UBERON:0004736	80.18	gold quality
transverse colon	UBERON:0001157	79.18	gold quality
gall bladder	UBERON:0002110	78.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.32	gold quality
cortex of kidney	UBERON:0001225	77.91	gold quality
metanephros cortex	UBERON:0010533	77.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.08	gold quality
small intestine	UBERON:0002108	76.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.66	gold quality
metanephros	UBERON:0000081	75.05	gold quality
jejunum	UBERON:0002115	73.65	gold quality
intestine	UBERON:0000160	72.55	gold quality
colonic epithelium	UBERON:0000397	71.82	gold quality
renal medulla	UBERON:0000362	71.51	gold quality
vermiform appendix	UBERON:0001154	71.15	gold quality
large intestine	UBERON:0000059	70.88	gold quality
colon	UBERON:0001155	69.86	gold quality
caecum	UBERON:0001153	68.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting LRRC19, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3686	99.90	70.53	2432

Literature-anchored findings (GeneRIF, showing 2)

• LRRC19 may play an important role in inducing innate immune responses in certain tissues such as the kidney. (PMID:19679103)
• LRRC19-A Bridge between Selenium Adjuvant Therapy and Renal Clear Cell Carcinoma: A Study Based on Datamining. (PMID:32316597)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc19	ENSMUSG00000049799
rattus_norvegicus	Lrrc19	ENSRNOG00000022225

Paralogs (22): DCN (ENSG00000011465), RTN4R (ENSG00000040608), ASPN (ENSG00000106819), FLRT3 (ENSG00000125848), FLRT1 (ENSG00000126500), LRRC4 (ENSG00000128594), LRRC4B (ENSG00000131409), PODNL1 (ENSG00000132000), LRTM1 (ENSG00000144771), LRRC4C (ENSG00000148948), LRRTM1 (ENSG00000162951), LRRC15 (ENSG00000172061), PODN (ENSG00000174348), LRRTM4 (ENSG00000176204), BGN (ENSG00000182492), FLRT2 (ENSG00000185070), GP1BA (ENSG00000185245), RTN4RL1 (ENSG00000185924), RTN4RL2 (ENSG00000186907), NYX (ENSG00000188937), LRRC66 (ENSG00000188993), LRRTM3 (ENSG00000198739)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 19 — Q9H756 (reviewed: Q9H756)

All UniProt accessions (1): Q9H756

UniProt curated annotations — full annotation on UniProt →

Function. Pathogen-recognition receptor which mediates the activation of TRAF2- and TRAF6 NF-kappa-B signaling pathways and induces the expression of pro-inflammatory cytokines. In kidney, prevents infection by uropathogenic bacteria by inducing the production of cytokines, chemokines and antimicrobial substances. In gut, involved in host-microbiota interactions, plays a critical role in promoting the recruitment of immune cells and intestinal inflammation.

Subunit / interactions. Interacts with TRAF2 and TRAF6.

Subcellular location. Membrane.

Tissue specificity. Expressed in renal collecting duct epithelial cells.

Activity regulation. Activated by TLR ligands such as LPS, bacterial DNA and peptidoglycan.

RefSeq proteins (1): NP_075052* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13855, PF15176

UniProt features (21 total): glycosylation site 10, repeat 5, topological domain 2, signal peptide 1, chain 1, domain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H756-F1	74.43	0.53

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 (10): 32, 37, 62, 95, 179, 192, 195, 202, 251, 256

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, MODULE_317, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_POSITIVE_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CYTOKINE_PRODUCTION, MODULE_301, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (6): regulation of cytokine production (GO:0001817), toll-like receptor signaling pathway (GO:0002224), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), host-mediated modulation of intestinal microbiota composition (GO:0048874), regulation of inflammatory response (GO:0050727), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)

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
positive regulation of intracellular signal transduction	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
pattern recognition receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
homeostasis of number of cells	1
host-mediated perturbation of symbiont process	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC19	TRMT11	Q7Z4G4	573
LRRC19	TMEM214	Q6NUQ4	524
LRRC19	IMMP2L	Q96T52	520
LRRC19	MOB3B	Q86TA1	505
LRRC19	ARMCX3	Q9UH62	482
LRRC19	KBTBD8	Q8NFY9	476
LRRC19	RIPK4	P57078	426
LRRC19	PLAA	Q9Y263	415
LRRC19	IFT74	Q96LB3	404
LRRC19	TUSC1	Q2TAM9	384
LRRC19	ZNF575	Q86XF7	377
LRRC19	C16orf89	Q6UX73	374
LRRC19	COMT	P21964	371
LRRC19	CD22	P20273	368
LRRC19	CLEC2L	P0C7M8	367

IntAct

3 interactions, top by confidence:

A	B	Type	Score
LRRC19		psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (1): LRRC19 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A2K5V015, A1YIY0, A8MUZ8, A8MWA4, B8JI71, O08569, P01133, P0DJ43, P14370, P14585, P17630, P19070, P48357, P82279, P97435, Q07444, Q0D2K5, Q28066, Q28660, Q29RU2, Q4KUS1, Q5G872, Q5R6R1, Q5RCW9, Q5T1H1, Q5UKY4, Q5Z5Q3, Q60736, Q63515, Q63722, Q6DFV8, Q6GMZ9, Q6V0K7, Q6ZN79, Q7TSY4, Q811Q4, Q8N2E2, Q8VHS2, Q90Y54, Q95MI4

Diamond homologs: Q6NUI6, Q8BZT5, Q9H756

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

627 predictions. Top by Δscore:

Variant	Effect	Δscore
9:26995864:C:CT	acceptor_gain	1.0000
9:26995864:C:T	acceptor_gain	1.0000
9:26995865:A:T	acceptor_gain	1.0000
9:26996495:ATTTT:A	acceptor_gain	1.0000
9:26996496:TTTT:T	acceptor_gain	1.0000
9:26996497:TTT:T	acceptor_gain	1.0000
9:26996498:TT:T	acceptor_gain	1.0000
9:26996499:TCTAG:T	acceptor_loss	1.0000
9:26996500:C:CC	acceptor_gain	1.0000
9:26996501:T:C	acceptor_loss	1.0000
9:26996503:G:GC	acceptor_gain	1.0000
9:26996509:C:CT	acceptor_gain	1.0000
9:26996510:A:T	acceptor_gain	1.0000
9:26999612:A:AC	donor_gain	1.0000
9:26999613:C:CC	donor_gain	1.0000
9:26999613:CT:C	donor_gain	1.0000
9:26995846:TGTT:T	acceptor_gain	0.9900
9:26995850:C:CC	acceptor_gain	0.9900
9:26995852:T:TC	acceptor_gain	0.9900
9:26995855:A:AC	acceptor_gain	0.9900
9:26995855:A:C	acceptor_gain	0.9900
9:26995860:A:AC	acceptor_gain	0.9900
9:26996503:G:C	acceptor_gain	0.9900
9:26999612:ACT:A	donor_gain	0.9900
9:26999613:CTC:C	donor_gain	0.9900
9:26995847:GTTC:G	acceptor_loss	0.9800
9:26995848:TT:T	acceptor_gain	0.9800
9:26995849:TC:T	acceptor_loss	0.9800
9:26995851:T:A	acceptor_loss	0.9800
9:26996305:TATTA:T	donor_loss	0.9800

AlphaMissense

2449 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:26997791:A:G	W178R	0.992
9:26997791:A:T	W178R	0.992
9:26997789:C:A	W178C	0.991
9:26997789:C:G	W178C	0.991
9:26998075:T:A	N83I	0.989
9:26998090:A:G	L78P	0.988
9:26996478:C:G	C206S	0.986
9:26996479:A:T	C206S	0.986
9:26997868:A:G	L152P	0.986
9:26997946:A:G	L126S	0.986
9:26998018:A:G	L102S	0.986
9:26998162:A:G	L54P	0.986
9:26998076:T:A	N83Y	0.984
9:26998168:A:G	L52P	0.984
9:26997783:G:C	C180W	0.983
9:26997858:A:C	N155K	0.983
9:26997858:A:T	N155K	0.983
9:26997795:G:C	N176K	0.982
9:26997795:G:T	N176K	0.982
9:26997930:G:C	N131K	0.982
9:26997930:G:T	N131K	0.982
9:26998074:G:C	N83K	0.982
9:26998074:G:T	N83K	0.982
9:26997874:A:G	L150P	0.981
9:26997931:T:A	N131I	0.979
9:26997940:A:G	L128P	0.979
9:26996477:A:C	C206W	0.978
9:26998002:G:C	N107K	0.978
9:26998002:G:T	N107K	0.978
9:26996479:A:G	C206R	0.976

dbSNP variants (sampled 300 via entrez): RS1000189768 (9:26999172 A>G), RS1000472215 (9:26992804 G>A), RS1000483613 (9:27000412 T>C), RS1000532138 (9:27000518 G>T), RS1000552661 (9:27004415 T>A,G), RS1000627019 (9:27000215 A>G), RS1000853965 (9:27000091 C>G), RS1000930996 (9:27004470 A>T), RS1000962216 (9:27004736 G>A), RS1001210926 (9:26994279 C>G), RS1001448837 (9:26998776 G>A), RS1001467651 (9:27007054 G>A,T), RS1001638954 (9:26993189 G>A), RS1001836006 (9:27005468 A>G), RS1001880141 (9:26998969 G>C)

Disease associations

OMIM: gene MIM:619068 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
Zoledronic Acid	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1
Cyclosporine	increases methylation	1
Aflatoxin M1	decreases expression	1

Clinical trials (associated diseases)

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