LRRC18

Summary

LRRC18 (leucine rich repeat containing 18, HGNC:23199) is a protein-coding gene on chromosome 10q11.23, encoding Leucine-rich repeat-containing protein 18 (Q8N456). May be involved in the regulation of spermatogenesis and sperm maturation.

Predicted to be involved in intracellular signal transduction. Predicted to be located in cytoplasm.

Source: NCBI Gene 474354 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_001378102

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23199
Approved symbol	LRRC18
Name	leucine rich repeat containing 18
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Aliases	UNQ933, MGC34773, UNQ9338, VKGE9338
Ensembl gene	ENSG00000165383
Ensembl biotype	protein_coding
OMIM	619002
Entrez	474354

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000374160

RefSeq mRNA: 2 — MANE Select: NM_001378102 NM_001006939, NM_001378102

CCDS: CCDS31197

Canonical transcript exons

ENST00000374160 — 4 exons

Exon	Start	End
ENSE00001092624	48913392	48914232
ENSE00001896040	48909480	48910258
ENSE00003973393	48935177	48935275
ENSE00003973394	48939746	48939840

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 93.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0274 / max 26.1629, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109320	0.0231	3
109318	0.0042	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	93.68	gold quality
bronchus	UBERON:0002185	91.74	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.59	gold quality
left testis	UBERON:0004533	82.67	gold quality
right testis	UBERON:0004534	82.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.93	gold quality
testis	UBERON:0000473	79.51	gold quality
epithelium of nasopharynx	UBERON:0001951	78.62	silver quality
right uterine tube	UBERON:0001302	70.58	gold quality
lower lobe of lung	UBERON:0008949	66.19	silver quality
germinal epithelium of ovary	UBERON:0001304	65.58	gold quality
nasal cavity mucosa	UBERON:0001826	62.58	gold quality
bone marrow cell	CL:0002092	62.56	silver quality
upper leg skin	UBERON:0004262	60.80	silver quality
superficial temporal artery	UBERON:0001614	60.09	gold quality
fallopian tube	UBERON:0003889	59.76	gold quality
oviduct epithelium	UBERON:0004804	58.91	gold quality
right lung	UBERON:0002167	58.62	gold quality
gingival epithelium	UBERON:0001949	58.31	gold quality
skin of hip	UBERON:0001554	58.18	silver quality
lung	UBERON:0002048	58.02	gold quality
upper lobe of lung	UBERON:0008948	57.41	gold quality
sperm	CL:0000019	57.14	gold quality
upper lobe of left lung	UBERON:0008952	56.83	gold quality
rectum	UBERON:0001052	56.28	gold quality
colonic epithelium	UBERON:0000397	55.60	gold quality
parietal pleura	UBERON:0002400	53.85	gold quality
gingiva	UBERON:0001828	53.17	gold quality
vermiform appendix	UBERON:0001154	52.24	gold quality
mucosa of transverse colon	UBERON:0004991	50.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting LRRC18, 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-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-377-3P	99.37	70.18	1905

Literature-anchored findings (GeneRIF, showing 1)

• Identification of key genes in coronary artery disease: an integrative approach based on weighted gene co-expression network analysis and their correlation with immune infiltration. (PMID:33686958)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc18b	ENSDARG00000076236
danio_rerio	lrrc18a	ENSDARG00000078790
mus_musculus	Lrrc18	ENSMUSG00000041673
rattus_norvegicus	Lrrc18	ENSRNOG00000020080

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), LRRC2 (ENSG00000163827), 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 18 — Q8N456 (reviewed: Q8N456)

All UniProt accessions (1): Q8N456

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the regulation of spermatogenesis and sperm maturation.

Subcellular location. Cytoplasm.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N456-1	1	yes
Q8N456-2	2

RefSeq proteins (2): NP_001006940, NP_001365031* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050216	LRR_domain-containing	Family
IPR055414	LRR_R13L4/SHOC2-like	Domain

Pfam: PF23598

UniProt features (12 total): repeat 7, sequence variant 2, chain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N456-F1	82.10	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIR340_5P, MIR877_3P, MIR6740_3P, MIR1264, MIR4796_5P, MIR5572, MIR8081, MIR1256, MIR3144_3P, MIR4721, GSE14308_TH1_VS_NATURAL_TREG_UP, GSE7596_AKT_TRANSD_VS_CTRL_CD4_TCONV_WITH_TGFB_UP, GSE10211_UV_INACT_SENDAI_VS_LIVE_SENDAI_VIRUS_TRACHEAL_EPITHELIAL_CELLS_UP, GSE10147_IL3_AND_HIVP17_VS_IL3_AND_CPG_STIM_PDC_UP

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

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

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
signal transduction	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC18	WDFY4	Q6ZS81	700
LRRC18	ATP6AP1L	Q52LC2	644
LRRC18	DRG2	P55039	605
LRRC18	RNF141	Q8WVD5	549
LRRC18	POLR2E	P19388	521
LRRC18	LRRC74B	Q6ZQY2	517
LRRC18	LMNTD1	Q8N9Z9	510
LRRC18	MAP7	Q14244	472
LRRC18	FAM170B	A6NMN3	451
LRRC18	AGAP6	Q5VW22	447
LRRC18	NDUFA7	O95182	427
LRRC18	XKR6	Q5GH73	425
LRRC18	DYNLT2	Q8IZS6	422
LRRC18	SPATA4	Q8NEY3	420
LRRC18	CCDC42	Q96M95	407

IntAct

16 interactions, top by confidence:

A	B	Type	Score
ZBTB24	LRRC18	psi-mi:“MI:0915”(physical association)	0.560
FRS3	LRRC18	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	LRRC18	psi-mi:“MI:0915”(physical association)	0.560
	CYB5B	psi-mi:“MI:0914”(association)	0.500
LRRC18	P4HB	psi-mi:“MI:0915”(physical association)	0.400
	LRRC18	psi-mi:“MI:0915”(physical association)	0.400
nleB1	LRRC18	psi-mi:“MI:0915”(physical association)	0.370
KCTD17	LRRC18	psi-mi:“MI:0915”(physical association)	0.370
LRRC18	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
FRS3	LRRC18	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): LRRC18 (Two-hybrid), LRRC18 (Two-hybrid), LRRC18 (Two-hybrid), LRRC18 (Two-hybrid), LRRC18 (Proximity Label-MS), LRRC18 (Negative Genetic), LRRC18 (Affinity Capture-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: Q66HD6, Q8N456, Q9CQ07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

332 predictions. Top by Δscore:

Variant	Effect	Δscore
10:48910259:C:CC	acceptor_gain	0.9800
10:48913359:T:A	donor_gain	0.9800
10:48913393:T:TA	donor_gain	0.9800
10:48910257:TT:T	acceptor_gain	0.9700
10:48913360:C:A	donor_gain	0.9700
10:48913402:C:A	donor_gain	0.9700
10:48910255:TATT:T	acceptor_gain	0.9500
10:48910258:TC:T	acceptor_loss	0.9500
10:48910259:CTG:C	acceptor_loss	0.9500
10:48910260:T:G	acceptor_loss	0.9500
10:48911977:C:CT	donor_gain	0.9500
10:48913401:T:TA	donor_gain	0.9500
10:48912580:C:T	donor_gain	0.9400
10:48913367:G:GA	donor_gain	0.9400
10:48913604:CTCA:C	donor_loss	0.9300
10:48913605:TCA:T	donor_loss	0.9300
10:48913606:CACCT:C	donor_loss	0.9300
10:48913607:ACC:A	donor_loss	0.9300
10:48913608:C:T	donor_loss	0.9300
10:48913608:CCTGG:C	donor_gain	0.9300
10:48910254:GTATT:G	acceptor_gain	0.9200
10:48910272:C:CT	acceptor_loss	0.9200
10:48911977:CCACT:C	donor_gain	0.9200
10:48913603:ACT:A	donor_loss	0.9200
10:48913344:C:A	donor_gain	0.9000
10:48910261:G:C	acceptor_loss	0.8900
10:48910273:A:T	acceptor_loss	0.8800
10:48913348:C:CA	donor_gain	0.8800
10:48913457:T:A	donor_gain	0.8800
10:48935490:G:T	donor_gain	0.8800

AlphaMissense

1736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:48913907:G:C	N83K	0.996
10:48913907:G:T	N83K	0.996
10:48913917:A:G	L80P	0.996
10:48913838:G:C	N106K	0.995
10:48913838:G:T	N106K	0.995
10:48913986:A:G	L57P	0.995
10:48913694:G:C	N154K	0.994
10:48913694:G:T	N154K	0.994
10:48913854:A:G	L101P	0.994
10:48913976:A:C	N60K	0.994
10:48913976:A:T	N60K	0.994
10:48913980:C:G	R59P	0.994
10:48914103:G:T	A18D	0.994
10:48913763:G:C	N131K	0.993
10:48913763:G:T	N131K	0.993
10:48913923:A:G	L78P	0.993
10:48913983:C:A	S58I	0.993
10:48913992:A:G	L55P	0.993
10:48914055:A:G	L34S	0.993
10:48913910:G:C	S82R	0.992
10:48913910:G:T	S82R	0.992
10:48913912:T:G	S82R	0.992
10:48914064:C:G	R31P	0.992
10:48913839:T:A	N106I	0.991
10:48913908:T:A	N83I	0.991
10:48913986:A:T	L57H	0.991
10:48913848:A:T	V103D	0.990
10:48913909:T:A	N83Y	0.990
10:48914061:A:G	L32P	0.990
10:48913704:A:G	L151P	0.989

dbSNP variants (sampled 300 via entrez): RS1000023381 (10:48931463 C>T), RS1000082851 (10:48924620 A>G), RS1000222920 (10:48931716 T>G), RS1000325950 (10:48909369 T>A), RS1000525956 (10:48940703 G>A), RS1000553286 (10:48915394 C>A,T), RS1000661861 (10:48910775 G>A), RS1000663222 (10:48910678 T>A), RS1000777332 (10:48910456 C>A), RS1000864461 (10:48941175 G>A,C), RS1000915256 (10:48940903 G>A), RS1000955515 (10:48929920 C>T), RS1001004232 (10:48935584 T>C), RS1001175769 (10:48925248 T>G), RS1001271326 (10:48924288 C>G)

Disease associations

OMIM: gene MIM:619002 | 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
GCST000087_5	Subclinical atherosclerosis traits (other)	2.000000e-06
GCST000507_14	Systemic lupus erythematosus	7.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004859	abdominal aortic artery calcification
EFO:0005278	cardiovascular disease biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydrogen Peroxide	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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