LRRC25

Summary

LRRC25 (leucine rich repeat containing 25, HGNC:29806) is a protein-coding gene on chromosome 19p13.11, encoding Leucine-rich repeat-containing protein 25 (Q8N386). Plays a role in the inhibition of RLR-mediated type I interferon signaling pathway by targeting RIGI for autophagic degradation.

Predicted to act upstream of or within several processes, including canonical NF-kappaB signal transduction; connective tissue replacement involved in inflammatory response wound healing; and response to angiotensin. Located in cytosol; endoplasmic reticulum; and microtubule cytoskeleton.

Source: NCBI Gene 126364 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_145256

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29806
Approved symbol	LRRC25
Name	leucine rich repeat containing 25
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	MAPA, FLJ38116
Ensembl gene	ENSG00000175489
Ensembl biotype	protein_coding
OMIM	607518
Entrez	126364

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000339007, ENST00000595840

RefSeq mRNA: 1 — MANE Select: NM_145256 NM_145256

CCDS: CCDS12377

Canonical transcript exons

ENST00000339007 — 2 exons

Exon	Start	End
ENSE00001183684	18396185	18397622
ENSE00003166670	18391137	18392125

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 97.51.

FANTOM5 (CAGE): breadth broad, TPM avg 10.2049 / max 638.6518, expressed in 433 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180000	10.0290	429
180001	0.0909	57
179999	0.0544	22
179998	0.0306	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.51	gold quality
leukocyte	CL:0000738	97.48	gold quality
granulocyte	CL:0000094	96.84	gold quality
blood	UBERON:0000178	94.44	gold quality
spleen	UBERON:0002106	91.68	gold quality
superficial temporal artery	UBERON:0001614	88.77	gold quality
vermiform appendix	UBERON:0001154	86.29	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.29	gold quality
gingival epithelium	UBERON:0001949	84.42	gold quality
germinal epithelium of ovary	UBERON:0001304	83.34	silver quality
bone marrow	UBERON:0002371	81.82	gold quality
bone marrow cell	CL:0002092	81.05	gold quality
lower lobe of lung	UBERON:0008949	79.45	silver quality
caecum	UBERON:0001153	79.13	gold quality
gingiva	UBERON:0001828	78.74	gold quality
left adrenal gland	UBERON:0001234	78.67	gold quality
upper lobe of lung	UBERON:0008948	78.67	gold quality
upper lobe of left lung	UBERON:0008952	78.56	gold quality
right adrenal gland cortex	UBERON:0035827	78.45	gold quality
left adrenal gland cortex	UBERON:0035825	78.27	gold quality
right adrenal gland	UBERON:0001233	78.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.53	gold quality
right coronary artery	UBERON:0001625	76.80	gold quality
adrenal cortex	UBERON:0001235	76.20	gold quality
adrenal gland	UBERON:0002369	75.10	gold quality
right lung	UBERON:0002167	74.72	gold quality
smooth muscle tissue	UBERON:0001135	74.36	gold quality
gall bladder	UBERON:0002110	74.24	gold quality
lymph node	UBERON:0000029	74.14	gold quality
omental fat pad	UBERON:0010414	73.22	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	63.49
E-CURD-122	yes	39.95
E-MTAB-9221	yes	26.46
E-MTAB-6678	yes	25.04
E-MTAB-9467	yes	17.91
E-MTAB-8498	yes	11.55
E-MTAB-9067	yes	10.69
E-MTAB-9801	yes	6.35
E-GEOD-110499	no	120.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting LRRC25, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-939-5P	97.10	65.80	1579

Literature-anchored findings (GeneRIF, showing 4)

• LRRC25, a potential leukocyte differentiation antigen, is a key regulator of all-trans retinoic acid-induced granulocytic differentiation (PMID:28536942)
• Our study has not only identified LRRC25 as a novel inhibitor of NF-kappaB signaling pathway, but also uncovers a new mechanism of crosstalk between NF-kappaB signaling and autophagy pathways. (PMID:29044191)
• The findings identify a previously unrecognized role of LRRC25 in type I interferon signaling activation by which LRRC25 acts as a secondary receptor to assist RIG-I delivery to autophagosomes for degradation in a p62-dependent manner. (PMID:29288164)
• LRRC25 as a critical molecular switch whose down-regulation resulted in cardiac hypertrophy in a TGF-beta1- and NF-kappaB-dependent manner. (PMID:30340835)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc25	ENSMUSG00000049988
rattus_norvegicus	Lrrc25	ENSRNOG00000022565

Protein

Protein identifiers

Leucine-rich repeat-containing protein 25 — Q8N386 (reviewed: Q8N386)

Alternative names: Monocyte and plasmacytoid-activated protein

All UniProt accessions (1): Q8N386

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the inhibition of RLR-mediated type I interferon signaling pathway by targeting RIGI for autophagic degradation. Interacts specifically with ISG15-associated RIGI to promote interaction between RIGI and the autophagic cargo receptor p62/SQSTM1 to mediate RIGI degradation via selective autophagy. Also plays a role in the inhibition of NF-kappa-B signaling pathway and inflammatory response by promoting the degradation of p65/RELA.

Subunit / interactions. Interacts with RIGI. Interacts with SQSTM1. Interacts with p65/RELA; this interaction promotes the degradation of RELA through autophagy.

Subcellular location. Membrane. Cytoplasm.

Tissue specificity. Expressed in plasmacytoid dendritic cells (PDC), monocyte-derived dendritic cells (MDDC), granulocytes, monocytes, B-lymphocytes, peripheral blood leukocytes, spleen, bone marrow, and, to a lesser extent, lymph nodes, fetal liver, and appendix but not in thymus.

Induction. Down-regulated in CD40-activated monocyte-derived dendritic cells.

RefSeq proteins (1): NP_660299* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR039243	LRRC25	Family

UniProt features (19 total): glycosylation site 4, sequence conflict 3, repeat 3, sequence variant 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N386-F1	70.48	0.38

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): 284

Glycosylation sites (4): 44, 55, 130, 148

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): MARSON_BOUND_BY_FOXP3_STIMULATED, chr19p13, VILIMAS_NOTCH1_TARGETS_DN, CHEN_METABOLIC_SYNDROM_NETWORK, STK33_NOMO_UP, STK33_UP, ZFP3_TARGET_GENES, ZNF436_TARGET_GENES, ZNF92_TARGET_GENES, MIR5688, MIR495_3P, MIR3529_3P, MIR3065_5P, MIR196A_1_3P, GSE11864_UNTREATED_VS_CSF1_IN_MAC_UP

GO Biological Process (0):

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

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC25	PGPEP1	Q9NXJ5	619
LRRC25	RIGI	O95786	615
LRRC25	SSBP4	Q9BWG4	495
LRRC25	UBL3	O95164	480
LRRC25	LRRC59	Q96AG4	476
LRRC25	RCCD1	A6NED2	465
LRRC25	GAL3ST4	Q96RP7	459
LRRC25	FN1	P02751	457
LRRC25	MSRB2	Q9Y3D2	440
LRRC25	CNBP	P20694	424
LRRC25	CHST8	Q9H2A9	423
LRRC25	B3GALT6	Q96L58	415
LRRC25	SLC4A3	P48751	404
LRRC25	SYDE2	Q5VT97	383
LRRC25	ARRDC2	Q8TBH0	368

IntAct

117 interactions, top by confidence:

A	B	Type	Score
PKMYT1	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
LHFPL5	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
TRAF3IP3	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	FATE1	psi-mi:“MI:0915”(physical association)	0.560
APOL3	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	AGPAT4	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	PKMYT1	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	GPRC5D	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	CLDN19	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	CLEC1A	psi-mi:“MI:0915”(physical association)	0.560
SPNS3	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
OPRM1	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
MAL	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	TMEM120A	psi-mi:“MI:0915”(physical association)	0.560
FPR2	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	CNIH3	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
VAMP5	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
TSPAN4	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
TTMP	LRRC25	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (186): LRRC25 (Affinity Capture-Western), ISG15 (Affinity Capture-Western), DDX58 (Affinity Capture-Western), LRRC25 (Affinity Capture-Western), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid), LRRC25 (Two-hybrid)

ESM2 similar proteins: A4F4L0, O00453, O14669, O43914, O54885, P04234, P04235, P07766, P0CAN6, P18438, P19377, P20963, P24161, P29328, P29329, P59646, Q13113, Q28072, Q28073, Q2KIP5, Q3TYX2, Q5R1Q1, Q5RA41, Q63113, Q64159, Q6AYD4, Q6ITQ4, Q6X9T7, Q764N2, Q8K1T1, Q8MII8, Q8N386, Q8NET5, Q8R182, Q8WNQ8, Q923S2, Q925F2, Q95J79, Q95LI5, Q95LI8

Diamond homologs: Q8K1T1, Q8MII8, Q8N386

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	41
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

289 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18392121:GAGCC:G	acceptor_gain	1.0000
19:18392123:GCC:G	acceptor_gain	1.0000
19:18392124:CC:C	acceptor_gain	1.0000
19:18392124:CCC:C	acceptor_gain	1.0000
19:18392125:CC:C	acceptor_gain	1.0000
19:18392126:C:CC	acceptor_gain	1.0000
19:18392126:C:T	acceptor_gain	1.0000
19:18392126:CTG:C	acceptor_loss	1.0000
19:18392122:AGCC:A	acceptor_gain	0.9900
19:18392123:GCCCT:G	acceptor_gain	0.9800
19:18392122:AGCCC:A	acceptor_gain	0.9700
19:18392124:CCCT:C	acceptor_gain	0.9700
19:18396183:AC:A	donor_gain	0.9700
19:18396184:CC:C	donor_gain	0.9700
19:18396179:ACTT:A	donor_loss	0.9500
19:18396180:CTT:C	donor_loss	0.9500
19:18396181:TTACC:T	donor_loss	0.9500
19:18396182:T:TG	donor_loss	0.9500
19:18396183:ACCCT:A	donor_loss	0.9500
19:18396184:C:G	donor_loss	0.9500
19:18397447:TCCTA:T	donor_loss	0.9500
19:18397448:CCTA:C	donor_loss	0.9500
19:18397449:CTACC:C	donor_loss	0.9500
19:18397450:TAC:T	donor_loss	0.9500
19:18397451:ACC:A	donor_loss	0.9500
19:18397452:C:G	donor_loss	0.9500
19:18392125:CCT:C	acceptor_gain	0.9400
19:18397453:C:G	donor_loss	0.9400
19:18396177:TTAC:T	donor_loss	0.9300
19:18396178:TACT:T	donor_loss	0.9300

AlphaMissense

1962 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18396595:C:A	W123C	0.994
19:18396595:C:G	W123C	0.994
19:18396862:C:A	W34C	0.992
19:18396862:C:G	W34C	0.992
19:18396597:A:G	W123R	0.983
19:18396597:A:T	W123R	0.983
19:18396767:A:T	L66H	0.982
19:18396704:A:T	L87H	0.976
19:18396830:A:G	F45S	0.976
19:18396864:A:G	W34R	0.976
19:18396864:A:T	W34R	0.976
19:18396508:G:C	F152L	0.975
19:18396508:G:T	F152L	0.975
19:18396510:A:G	F152L	0.975
19:18396679:G:C	N95K	0.975
19:18396679:G:T	N95K	0.975
19:18396761:A:G	L68P	0.975
19:18396548:C:G	C139S	0.974
19:18396549:A:T	C139S	0.974
19:18396761:A:T	L68Q	0.973
19:18396695:A:G	L90P	0.970
19:18396547:G:C	C139W	0.967
19:18396681:T:C	N95D	0.965
19:18396722:A:C	F81C	0.965
19:18396724:G:C	F80L	0.965
19:18396724:G:T	F80L	0.965
19:18396726:A:G	F80L	0.965
19:18396695:A:T	L90Q	0.963
19:18396850:G:C	F38L	0.962
19:18396850:G:T	F38L	0.962

dbSNP variants (sampled 300 via entrez): RS1000349753 (19:18398854 T>C), RS1000402802 (19:18393410 G>A,C), RS1000433995 (19:18393158 G>A), RS1000440330 (19:18393944 G>A), RS1000938683 (19:18395251 G>A,C), RS1000953590 (19:18397411 G>C), RS1001257293 (19:18394309 T>TTTC), RS1001281140 (19:18397708 C>T), RS1001614299 (19:18392850 C>A,T), RS1001710442 (19:18398808 G>A), RS1001785811 (19:18398553 G>T), RS1002221096 (19:18399087 CTGTT>C), RS1002369797 (19:18398577 T>C), RS1002422090 (19:18398783 T>C), RS1002565040 (19:18391854 G>A)

Disease associations

OMIM: gene MIM:607518 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004609_98	Monocyte percentage of white cells	1.000000e-27
GCST005752_105	Systemic lupus erythematosus	1.000000e-08
GCST005929_1	Severity of nausea and vomiting of pregnancy	2.000000e-41
GCST005930_1	Hyperemesis gravidarum	2.000000e-19
GCST007400_25	Systemic lupus erythematosus	7.000000e-07
GCST010989_289	Body size at age 10	5.000000e-13
GCST011096_19	Systemic lupus erythematosus	1.000000e-10
GCST011097_3	Systemic lupus erythematosus	2.000000e-06
GCST90002394_551	Monocyte percentage of white cells	3.000000e-76
GCST90002407_370	White blood cell count	1.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0009265	nausea and vomiting of pregnancy severity measurement
EFO:0009819	comparative body size at age 10, self-reported

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
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	7
Tetrachlorodibenzodioxin	increases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
pinosylvin	increases expression	1
(+)-JQ1 compound	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Iron	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	decreases methylation	1
Methotrexate	decreases expression	1
Nickel	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Vitamin D	affects expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
beta-Naphthoflavone	increases expression	1

Clinical trials (associated diseases)

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