LRRC3C

Summary

LRRC3C (leucine rich repeat containing 3C, HGNC:40034) is a protein-coding gene on chromosome 17q21.1, encoding Leucine-rich repeat-containing protein 3C (A6NJW4).

Predicted to be located in membrane. Predicted to be active in extracellular matrix and extracellular space.

Source: NCBI Gene 100505591 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_001195545

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40034
Approved symbol	LRRC3C
Name	leucine rich repeat containing 3C
Location	17q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204913
Ensembl biotype	protein_coding
Entrez	100505591

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377924

RefSeq mRNA: 1 — MANE Select: NM_001195545 NM_001195545

CCDS: CCDS54121

Canonical transcript exons

ENST00000377924 — 4 exons

Exon	Start	End
ENSE00001475527	39943933	39944999
ENSE00001605552	39941443	39941549
ENSE00003919515	39935802	39935894
ENSE00003921264	39927732	39927814

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 49.30.

FANTOM5 (CAGE): breadth broad, TPM avg 0.3653 / max 9.7920, expressed in 207 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160644	0.3653	207

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	49.30	gold quality
stromal cell of endometrium	CL:0002255	40.25	gold quality
bone marrow cell	CL:0002092	38.51	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
left testis	UBERON:0004533	37.14	gold quality
testis	UBERON:0000473	36.77	silver quality
vermiform appendix	UBERON:0001154	36.77	silver quality
mucosa of stomach	UBERON:0001199	36.52	silver quality
left uterine tube	UBERON:0001303	36.52	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skeletal muscle tissue	UBERON:0001134	36.40	gold quality
fallopian tube	UBERON:0003889	35.72	gold quality
bone marrow	UBERON:0002371	35.51	gold quality
right testis	UBERON:0004534	35.51	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right uterine tube	UBERON:0001302	34.94	gold quality
muscle tissue	UBERON:0002385	34.52	gold quality
endocervix	UBERON:0000458	34.03	silver quality
fundus of stomach	UBERON:0001160	34.01	gold quality
right ovary	UBERON:0002118	33.96	gold quality
skin of leg	UBERON:0001511	33.90	silver quality
islet of Langerhans	UBERON:0000006	33.79	gold quality
prefrontal cortex	UBERON:0000451	33.10	silver quality
zone of skin	UBERON:0000014	32.63	gold quality
uterine cervix	UBERON:0000002	32.60	silver quality
urinary bladder	UBERON:0001255	32.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
body of stomach	UBERON:0001161	31.69	silver quality
lymph node	UBERON:0000029	31.53	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.66

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Based on our results and published findings on GSDMA, GSDMB, LRRC3C, and related proteins, we propose that this locus in part affects IBD susceptibility via effects on apoptosis and cell proliferation (PMID:26484354)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc3c	ENSMUSG00000086545
rattus_norvegicus	Lrrc3c	ENSRNOG00000069314

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), LRRC3B (ENSG00000179796), TSKU (ENSG00000182704), TLR5 (ENSG00000187554), TLR7 (ENSG00000196664), LRIT2 (ENSG00000204033)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 3C — A6NJW4 (reviewed: A6NJW4)

All UniProt accessions (1): A6NJW4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the LRRC3 family.

RefSeq proteins (1): NP_001182474* (*=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
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF13855

UniProt features (9 total): repeat 3, domain 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NJW4-F1	79.40	0.54

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 (1): 156

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 3 (showing top): ZAK_PBMC_MRKAD5_HIV_1_GAG_POL_NEF_AGE_20_50YO_CORRELATED_WITH_CD8_T_CELL_RESPONSE_3DY_NEGATIVE, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY, chr17q21

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

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC3C	ZPBP2	Q6X784	718
LRRC3C	GSDMB	Q8TAX9	617
LRRC3C	ORMDL3	Q8N138	606
LRRC3C	GSDMA	Q96QA5	598
LRRC3C	CDRT15L2	A8MXV6	572
LRRC3C	TRAPPC12	Q8WVT3	525
LRRC3C	TMEM86A	Q8N2M4	485
LRRC3C	TBC1D28	Q2M2D7	480
LRRC3C	IKZF3	Q9UKT9	465
LRRC3C	CCDC144A	A2RUR9	450
LRRC3C	SLC35G6	P0C7Q6	449
LRRC3C	SLC35G3	Q8N808	448
LRRC3C	SPDYE4	A6NLX3	446
LRRC3C	OR3A2	P47893	445
LRRC3C	CHCT1	Q86WR6	436

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DLG1	LRRC3C	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1): S (Reconstituted Complex)

ESM2 similar proteins: A2AIG8, A5D7H1, A6H7A0, A6NFX1, A6NJW4, A8MUP2, A8MXK1, B0BMW8, O35393, O54804, O73884, P01135, P35790, P52875, P57791, Q00961, Q01098, Q01134, Q06922, Q08DW9, Q0P5M9, Q0VDI3, Q14728, Q14957, Q15768, Q2M1K6, Q3UGX3, Q4R7M4, Q4V899, Q5E9H2, Q5M7U7, Q5R6I6, Q5RCI5, Q5ZI20, Q7TPB4, Q8BZH0, Q8IVW8, Q8N431, Q8NBA8, Q8R2R5

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, A2AJ76, A4IFA6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

327 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39941548:GT:G	donor_gain	1.0000
17:39941546:TCGTG:T	donor_loss	0.9900
17:39941549:TG:T	donor_loss	0.9900
17:39941550:G:GG	donor_gain	0.9900
17:39941550:GT:G	donor_loss	0.9900
17:39941551:T:TG	donor_loss	0.9900
17:39941552:AA:A	donor_loss	0.9900
17:39941545:TTCGT:T	donor_gain	0.9800
17:39941546:TCGT:T	donor_gain	0.9800
17:39941547:CGT:C	donor_gain	0.9700
17:39941548:GTG:G	donor_gain	0.9700
17:39941549:TGT:T	donor_gain	0.9700
17:39941553:AGTA:A	donor_loss	0.9600
17:39941550:GTA:G	donor_gain	0.9300
17:39941554:G:C	donor_loss	0.9300
17:39942158:G:GT	donor_gain	0.9000
17:39943931:A:AG	acceptor_gain	0.9000
17:39943932:G:GG	acceptor_gain	0.9000
17:39942163:C:A	donor_gain	0.8700
17:39943927:CCCCA:C	acceptor_loss	0.8700
17:39943929:CCA:C	acceptor_loss	0.8700
17:39941554:G:GG	donor_gain	0.8400
17:39941553:A:AG	donor_gain	0.8300
17:39943932:GATC:G	acceptor_gain	0.8300
17:39942804:G:GT	donor_gain	0.8200
17:39942161:G:GG	donor_gain	0.7600
17:39942160:A:AG	donor_gain	0.7500
17:39942769:G:GT	donor_gain	0.7300
17:39942719:A:T	donor_gain	0.7100
17:39944640:G:T	acceptor_gain	0.7000

AlphaMissense

1734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39944392:G:C	W162C	0.990
17:39944392:G:T	W162C	0.990
17:39944202:T:G	F99C	0.988
17:39944274:T:G	F123C	0.988
17:39944319:A:T	N138I	0.983
17:39944229:T:C	L108S	0.982
17:39944235:T:C	L110P	0.982
17:39944274:T:C	F123S	0.982
17:39944390:T:A	W162R	0.982
17:39944390:T:C	W162R	0.982
17:39944202:T:C	F99S	0.981
17:39944397:G:A	C164Y	0.981
17:39944310:T:A	L135H	0.979
17:39944099:T:A	C65S	0.976
17:39944100:G:C	C65S	0.976
17:39944245:T:A	N113K	0.976
17:39944245:T:G	N113K	0.976
17:39944318:A:T	N138Y	0.976
17:39944320:C:A	N138K	0.976
17:39944320:C:G	N138K	0.976
17:39944386:C:A	N160K	0.976
17:39944386:C:G	N160K	0.976
17:39944384:A:T	N160Y	0.975
17:39944465:T:A	C187S	0.975
17:39944466:G:C	C187S	0.975
17:39944243:A:T	N113Y	0.974
17:39944244:A:T	N113I	0.974
17:39944396:T:A	C164S	0.974
17:39944397:G:C	C164S	0.974
17:39944201:T:C	F99L	0.973

dbSNP variants (sampled 300 via entrez): RS1000273437 (17:39943675 A>T), RS1000331439 (17:39936083 T>C), RS1000503191 (17:39938005 G>A), RS1000550125 (17:39932449 A>G), RS1000570647 (17:39936759 G>A), RS1000787457 (17:39936301 T>G), RS1001017987 (17:39932433 G>A), RS1001178786 (17:39926998 G>C), RS1001335386 (17:39933546 A>G), RS1001523729 (17:39938295 G>A), RS1001526377 (17:39944005 G>T), RS1001630188 (17:39926700 C>T), RS1001861715 (17:39944787 T>C), RS1001888607 (17:39939473 A>G,T), RS1002311108 (17:39945487 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004131_33	Inflammatory bowel disease	2.000000e-26
GCST004132_116	Crohn’s disease	1.000000e-16
GCST004133_16	Ulcerative colitis	2.000000e-16
GCST004202_2	Systemic sclerosis	1.000000e-10
GCST007564_21	Asthma or allergic disease (pleiotropy)	4.000000e-17
GCST008103_61	Bipolar disorder	6.000000e-07
GCST008916_21	Asthma	2.000000e-62
GCST009798_11	Asthma	1.000000e-65
GCST010002_123	Refractive error	1.000000e-24

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
2-palmitoylglycerol	increases expression	1

Clinical trials (associated diseases)

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