LRRC69

Summary

LRRC69 (leucine rich repeat containing 69, HGNC:34303) is a protein-coding gene on chromosome 8q21.3, encoding Leucine-rich repeat-containing protein 69 (Q6ZNQ3).

Predicted to be involved in intracellular signal transduction.

Source: NCBI Gene 100130742 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 75 total
• MANE Select transcript: NM_001129890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34303
Approved symbol	LRRC69
Name	leucine rich repeat containing 69
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000214954
Ensembl biotype	protein_coding
Entrez	100130742

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000343709, ENST00000448384, ENST00000518304, ENST00000518487, ENST00000520099, ENST00000521519, ENST00000522144

RefSeq mRNA: 2 — MANE Select: NM_001129890 NM_001129890, NM_001354470

CCDS: CCDS87619

Canonical transcript exons

ENST00000448384 — 8 exons

Exon	Start	End
ENSE00001330869	91102619	91102844
ENSE00001377259	91218890	91219257
ENSE00001666205	91124493	91124619
ENSE00003520076	91189522	91189623
ENSE00003555923	91200613	91200792
ENSE00003582504	91135668	91135739
ENSE00003630598	91127088	91127160
ENSE00003647352	91133110	91133305

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 84.87.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.90	gold quality
calcaneal tendon	UBERON:0003701	78.45	gold quality
endometrium	UBERON:0001295	75.66	gold quality
corpus callosum	UBERON:0002336	74.11	gold quality
lower esophagus mucosa	UBERON:0035834	73.97	gold quality
monocyte	CL:0000576	72.56	gold quality
smooth muscle tissue	UBERON:0001135	72.49	gold quality
stromal cell of endometrium	CL:0002255	72.44	gold quality
right lobe of thyroid gland	UBERON:0001119	72.44	gold quality
lymph node	UBERON:0000029	72.37	gold quality
right uterine tube	UBERON:0001302	72.28	gold quality
leukocyte	CL:0000738	72.24	gold quality
left lobe of thyroid gland	UBERON:0001120	71.56	gold quality
body of pancreas	UBERON:0001150	71.44	gold quality
thyroid gland	UBERON:0002046	71.41	gold quality
tonsil	UBERON:0002372	71.19	gold quality
spleen	UBERON:0002106	71.10	gold quality
lower esophagus	UBERON:0013473	70.84	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.83	gold quality
tibial nerve	UBERON:0001323	70.81	gold quality
skin of abdomen	UBERON:0001416	70.70	gold quality
zone of skin	UBERON:0000014	70.69	gold quality
skin of leg	UBERON:0001511	70.62	gold quality
metanephros cortex	UBERON:0010533	70.60	gold quality
fundus of stomach	UBERON:0001160	70.47	gold quality
right adrenal gland cortex	UBERON:0035827	70.31	gold quality
rectum	UBERON:0001052	70.12	gold quality
testis	UBERON:0000473	70.07	gold quality
mucosa of transverse colon	UBERON:0004991	70.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting LRRC69, 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-6835-3P	99.93	70.49	2904
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4473	98.89	69.10	652
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-1292-5P	96.74	62.14	238
HSA-MIR-4761-3P	96.27	66.26	524
HSA-MIR-8059	95.11	66.30	646

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc69	ENSMUSG00000023151
rattus_norvegicus	Lrrc69	ENSRNOG00000006498
caenorhabditis_elegans		WBGENE00002632

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), LRRC18 (ENSG00000165383), LRRC28 (ENSG00000168904), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), LRRC8D (ENSG00000171492), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 69 — Q6ZNQ3 (reviewed: Q6ZNQ3)

All UniProt accessions (3): E5RHQ9, E5RJ66, Q6ZNQ3

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the LRRC69 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZNQ3-1	1	yes
Q6ZNQ3-2	2

RefSeq proteins (2): NP_001123362, NP_001341399 (=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

Pfam: PF13855

UniProt features (11 total): repeat 8, chain 1, sequence variant 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZNQ3-F1	91.65	0.63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 16 (showing top): chr8q21, MIR6875_3P, GSE12366_GC_VS_MEMORY_BCELL_DN, MIR1292_5P, GSE10147_IL3_VS_IL3_AND_CPG_STIM_PDC_UP, DESCARTES_FETAL_PANCREAS_LYMPHATIC_ENDOTHELIAL_CELLS, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_4H_ACT_CD4_TCELL_DN, GSE1112_OT1_VS_HY_CD8AB_THYMOCYTE_RTOC_CULTURE_UP, GSE2128_CTRL_VS_MIMETOPE_NEGATIVE_SELECTION_DP_THYMOCYTE_NOD_DN, GSE6674_PL2_3_VS_ANTI_IGM_AND_CPG_STIM_BCELL_UP, GSE16385_MONOCYTE_VS_MACROPHAGE_DN, GSE28737_FOLLICULAR_VS_MARGINAL_ZONE_BCELL_DN, GSE46606_UNSTIM_VS_CD40L_IL2_IL5_3DAY_STIMULATED_IRF4_KO_BCELL_DN, GSE41176_UNSTIM_VS_ANTI_IGM_STIM_TAK1_KO_BCELL_1H_DN, GSE41176_WT_VS_TAK1_KO_ANTI_IGM_STIM_BCELL_1H_DN

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

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	1
signal transduction	1
binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TNFAIP3	FZD7	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): LRRC69 (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: Q3KQF4, Q6ZNQ3, Q9D9Q0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2018 predictions. Top by Δscore:

Variant	Effect	Δscore
8:91124491:A:AG	acceptor_gain	1.0000
8:91124492:G:GG	acceptor_gain	1.0000
8:91135737:GGA:G	donor_gain	1.0000
8:91135738:GA:G	donor_gain	1.0000
8:91135738:GAG:G	donor_gain	1.0000
8:91135740:G:GG	donor_gain	1.0000
8:91189645:T:G	donor_gain	1.0000
8:91189645:T:TG	donor_gain	1.0000
8:91200606:A:AG	acceptor_gain	1.0000
8:91200608:TTTA:T	acceptor_loss	1.0000
8:91200609:TTA:T	acceptor_loss	1.0000
8:91200610:TAGGA:T	acceptor_loss	1.0000
8:91200611:A:T	acceptor_loss	1.0000
8:91200611:AG:A	acceptor_gain	1.0000
8:91200612:GG:G	acceptor_gain	1.0000
8:91200612:GGAA:G	acceptor_gain	1.0000
8:91200788:CAAAG:C	donor_loss	1.0000
8:91200789:AAAG:A	donor_loss	1.0000
8:91200793:G:GA	donor_loss	1.0000
8:91200794:T:G	donor_loss	1.0000
8:91124492:GTT:G	acceptor_gain	0.9900
8:91124637:G:GT	donor_gain	0.9900
8:91133108:A:AG	acceptor_gain	0.9900
8:91133109:G:GG	acceptor_gain	0.9900
8:91133304:AGG:A	donor_loss	0.9900
8:91133306:GTAA:G	donor_loss	0.9900
8:91133307:TAAG:T	donor_loss	0.9900
8:91135660:T:A	acceptor_gain	0.9900
8:91135735:CAGGA:C	donor_gain	0.9900
8:91135736:AGGA:A	donor_gain	0.9900

AlphaMissense

2280 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:91124572:T:C	L88P	0.960
8:91135715:T:A	N209K	0.955
8:91135715:T:G	N209K	0.955
8:91124503:T:C	L65P	0.954
8:91124588:T:A	N93K	0.953
8:91124588:T:G	N93K	0.953
8:91127118:T:C	L114P	0.953
8:91127112:T:C	L112P	0.951
8:91124519:C:A	N70K	0.948
8:91124519:C:G	N70K	0.948
8:91127128:T:A	N117K	0.947
8:91127128:T:G	N117K	0.947
8:91124593:T:C	I95T	0.946
8:91133199:T:C	L158P	0.945
8:91124494:T:C	L62S	0.941
8:91102802:C:A	N47K	0.924
8:91102802:C:G	N47K	0.924
8:91133205:T:C	L160P	0.924
8:91133284:C:A	N186K	0.924
8:91133284:C:G	N186K	0.924
8:91133146:C:A	N140K	0.923
8:91133146:C:G	N140K	0.923
8:91133215:T:A	N163K	0.923
8:91133215:T:G	N163K	0.923
8:91127103:T:C	L109S	0.921
8:91124509:T:C	L67P	0.917
8:91200775:T:C	F306L	0.917
8:91200777:T:A	F306L	0.917
8:91200777:T:G	F306L	0.917
8:91133132:A:C	S136R	0.916

dbSNP variants (sampled 300 via entrez): RS1000020769 (8:91191097 C>G), RS1000074558 (8:91191346 T>A,C), RS1000096778 (8:91214661 T>C), RS1000131594 (8:91134079 G>T), RS1000132376 (8:91140029 G>A,T), RS1000164031 (8:91134426 G>A,C), RS1000242904 (8:91184095 T>C), RS1000245794 (8:91176470 A>C,G), RS1000256735 (8:91101509 A>G), RS1000258490 (8:91152305 A>C,G), RS1000291968 (8:91107935 C>T), RS1000316590 (8:91138830 A>G), RS1000322077 (8:91202077 G>A,T), RS1000342683 (8:91126969 C>A,T), RS1000383991 (8:91120752 A>G)

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

3 associations (top):

Study	Trait	p-value
GCST003542_6	Night sleep phenotypes	7.000000e-07
GCST006629_64	Pulse pressure	6.000000e-22
GCST90000025_368	Appendicular lean mass	2.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases methylation	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Valproic Acid	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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