LRRC17

Summary

LRRC17 (leucine rich repeat containing 17, HGNC:16895) is a protein-coding gene on chromosome 7q22.1, encoding Leucine-rich repeat-containing protein 17 (Q8N6Y2). Involved in bone homeostasis.

Predicted to be involved in bone marrow development and negative regulation of osteoclast differentiation. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix and extracellular space.

Source: NCBI Gene 10234 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001031692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16895
Approved symbol	LRRC17
Name	leucine rich repeat containing 17
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	P37NB, H_RG318M05.3
Ensembl gene	ENSG00000128606
Ensembl biotype	protein_coding
OMIM	618749
Entrez	10234

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000249377, ENST00000339431, ENST00000455453, ENST00000485478, ENST00000498487, ENST00000875757, ENST00000875758, ENST00000965933

RefSeq mRNA: 2 — MANE Select: NM_001031692 NM_001031692, NM_005824

CCDS: CCDS34721, CCDS5727

Canonical transcript exons

ENST00000339431 — 4 exons

Exon	Start	End
ENSE00001364991	102933774	102934685
ENSE00001516446	102913000	102913145
ENSE00003645513	102939430	102939585
ENSE00003645974	102944210	102945111

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.70.

FANTOM5 (CAGE): breadth broad, TPM avg 18.3422 / max 620.1543, expressed in 837 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80263	10.1932	721
80264	6.5970	629
80262	1.0765	266
80265	0.3708	155
80266	0.1047	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.70	gold quality
oocyte	CL:0000023	97.92	gold quality
periodontal ligament	UBERON:0008266	96.57	gold quality
right coronary artery	UBERON:0001625	94.57	gold quality
left ovary	UBERON:0002119	94.00	gold quality
right ovary	UBERON:0002118	93.04	gold quality
ventricular zone	UBERON:0003053	92.80	gold quality
ovary	UBERON:0000992	92.47	gold quality
descending thoracic aorta	UBERON:0002345	92.29	gold quality
gall bladder	UBERON:0002110	89.80	gold quality
blood vessel layer	UBERON:0004797	88.86	gold quality
coronary artery	UBERON:0001621	88.63	gold quality
vena cava	UBERON:0004087	88.59	gold quality
thoracic aorta	UBERON:0001515	88.33	gold quality
left coronary artery	UBERON:0001626	88.26	gold quality
ascending aorta	UBERON:0001496	88.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.69	gold quality
buccal mucosa cell	CL:0002336	87.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.45	gold quality
ganglionic eminence	UBERON:0004023	85.59	gold quality
tibia	UBERON:0000979	85.46	gold quality
calcaneal tendon	UBERON:0003701	85.18	gold quality
mammary duct	UBERON:0001765	83.89	gold quality
parietal pleura	UBERON:0002400	83.69	gold quality
stromal cell of endometrium	CL:0002255	83.57	gold quality
skin of hip	UBERON:0001554	83.56	gold quality
endocervix	UBERON:0000458	83.53	gold quality
mammalian vulva	UBERON:0000997	83.44	gold quality
adrenal tissue	UBERON:0018303	83.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	1078.90
E-HCAD-10	yes	60.43
E-ANND-3	yes	5.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting LRRC17, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914

Literature-anchored findings (GeneRIF, showing 4)

• Whole-genome microarray mRNA-expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly differentially expressed in these two cell types: NKX2-3 and LRRC17 in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts (PMID:27036009)
• low circulating plasma level of LRRc17 might serve as an independent and additive risk factor for osteoporotic fractures. (PMID:27355564)
• LRRC17 Is Linked to Prognosis of Ovarian Cancer Through a p53-dependent Anti-apoptotic Function. (PMID:32988884)
• LRRc17 controls BMSC senescence via mitophagy and inhibits the therapeutic effect of BMSCs on ovariectomy-induced bone loss. (PMID:33865167)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc17	ENSDARG00000037960
mus_musculus	Lrrc17	ENSMUSG00000039883
rattus_norvegicus	Lrrc17	ENSRNOG00000012817

Paralogs (22): IGFALS (ENSG00000099769), TLR8 (ENSG00000101916), 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), LRRC3C (ENSG00000204913)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 17 — Q8N6Y2 (reviewed: Q8N6Y2)

Alternative names: p37NB

All UniProt accessions (2): Q8N6Y2, C9JT74

UniProt curated annotations — full annotation on UniProt →

Function. Involved in bone homeostasis. Acts as a negative regulator of RANKL-induced osteoclast precursor differentiation from bone marrow precursors.

Subcellular location. Secreted. Extracellular space.

Tissue specificity. Expressed in osteoblast cell lines. Well expressed in ovary, heart, pancreas, skeletal muscle, lung, and fetal kidney and lung and only at the basal levels in the other tissues examined including adult kidney. More expressed in S-type neuroblastoma cells than in N-type neuroblastoma cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N6Y2-1	1	yes
Q8N6Y2-2	2

RefSeq proteins (2): NP_001026862, NP_005815 (=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
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF13855

UniProt features (17 total): repeat 6, domain 3, sequence variant 3, splice variant 2, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6Y2-F1	78.90	0.59

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, HORIUCHI_WTAP_TARGETS_DN, ACTACCT_MIR196A_MIR196B, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_OSTEOBLAST_DIFFERENTIATION, GNF2_PTX3, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_BONE_DEVELOPMENT

GO Biological Process (3): ossification (GO:0001503), negative regulation of osteoclast differentiation (GO:0045671), bone marrow development (GO:0048539)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	1
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
tissue development	1
hematopoietic or lymphoid organ development	1
bone development	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC17	FBXL13	Q8NEE6	572
LRRC17	CCDC69	A6NI79	455
LRRC17	SIX4	Q9UIU6	453
LRRC17	E2F8	A0AVK6	437
LRRC17	RENBP	P51606	430
LRRC17	PLEKHH2	Q8IVE3	423
LRRC17	SESTD1	Q86VW0	407
LRRC17	NFIB	O00712	406
LRRC17	GAS2L3	Q86XJ1	404
LRRC17	MEIS1	O00470	398
LRRC17	PBX2	P40425	398
LRRC17	PBX1	P40424	394
LRRC17	EBF2	Q9HAK2	394
LRRC17	CDO1	P78513	387
LRRC17	SATB2	Q9UPW6	387

IntAct

4 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350
LRRC17	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): LRRC17 (Protein-RNA), C1QBP (Affinity Capture-MS), CNPY3 (Affinity Capture-MS), CNPY4 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), TEFM (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), PRKCI (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), BCL7B (Affinity Capture-MS), MPO (Affinity Capture-MS)

ESM2 similar proteins: C0STK7, C3YZ59, O00206, O15455, O42235, O60938, O62702, O93233, P58727, Q0PV50, Q2V898, Q45R42, Q58A48, Q5BK65, Q5M7S9, Q5TJ59, Q62192, Q65YW8, Q65Z91, Q68Y56, Q6AXL3, Q6DF55, Q6R5N8, Q6R5P0, Q7Z2Q7, Q80X72, Q8BMT4, Q8BZT5, Q8C031, Q8N6Y2, Q8R5M3, Q8SPE8, Q8SPE9, Q965M2, Q99467, Q99MB1, Q99PH1, Q9CQ76, Q9CXD9, Q9DE66

Diamond homologs: O15335, O55226, O70210, O94933, O94991, Q27972, Q5RAC4, Q6RKD8, Q7M6Z0, Q7Z2Q7, Q80WD1, Q810B7, Q810B8, Q810B9, Q810C0, Q810C1, Q86UN3, Q8BGX3, Q8C110, Q8IW52, Q8N6Y2, Q8N967, Q96PX8, Q9H156, Q9H5Y7, Q9HBL6, Q9NZU1, B1H134, B1H234, Q5R6T0, Q70AK3, Q8BGT1, Q9CQ76, Q9CXD9, Q9NZU0, D3ZTV3, D4ABX8, E5DHB5, F1NUK7, F7D3V9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1366 predictions. Top by Δscore:

Variant	Effect	Δscore
7:102913213:TGC:T	acceptor_gain	1.0000
7:102913216:C:CC	acceptor_gain	1.0000
7:102926372:ATCC:A	acceptor_loss	1.0000
7:102926373:TC:T	acceptor_gain	1.0000
7:102926373:TCCTG:T	acceptor_loss	1.0000
7:102926374:CC:C	acceptor_gain	1.0000
7:102926375:C:CC	acceptor_gain	1.0000
7:102926376:T:C	acceptor_loss	1.0000
7:102927069:CA:C	acceptor_gain	1.0000
7:102939428:A:AG	acceptor_gain	1.0000
7:102939429:G:GG	acceptor_gain	1.0000
7:102939429:GA:G	acceptor_gain	1.0000
7:102939429:GAGTT:G	acceptor_gain	1.0000
7:102939581:TCCTG:T	donor_gain	1.0000
7:102939582:CCTG:C	donor_gain	1.0000
7:102939583:CTG:C	donor_gain	1.0000
7:102939584:TG:T	donor_gain	1.0000
7:102939585:GG:G	donor_gain	1.0000
7:102939585:GGTA:G	donor_loss	1.0000
7:102939586:G:GA	donor_loss	1.0000
7:102939586:G:GG	donor_gain	1.0000
7:102939587:TAAGT:T	donor_loss	1.0000
7:102913211:AGTGC:A	acceptor_gain	0.9900
7:102913212:GTGC:G	acceptor_gain	0.9900
7:102913214:GC:G	acceptor_gain	0.9900
7:102913215:CC:C	acceptor_gain	0.9900
7:102913217:T:C	acceptor_loss	0.9900
7:102926269:ATTAC:A	donor_loss	0.9900
7:102926270:TTA:T	donor_loss	0.9900
7:102926271:TA:T	donor_loss	0.9900

AlphaMissense

2922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:102934248:T:C	L112P	1.000
7:102934314:T:C	L134P	1.000
7:102944413:T:A	C378S	1.000
7:102944414:G:C	C378S	1.000
7:102934242:T:C	L110P	0.999
7:102934257:A:T	N115I	0.999
7:102934258:T:A	N115K	0.999
7:102934258:T:G	N115K	0.999
7:102934320:T:C	L136P	0.999
7:102934329:A:T	N139I	0.999
7:102934330:C:A	N139K	0.999
7:102934330:C:G	N139K	0.999
7:102934386:T:C	L158P	0.999
7:102934406:T:A	W165R	0.999
7:102934406:T:C	W165R	0.999
7:102934487:T:A	C192S	0.999
7:102934488:G:C	C192S	0.999
7:102939553:T:C	L299P	0.999
7:102944335:T:A	W352R	0.999
7:102944335:T:C	W352R	0.999
7:102944341:T:A	C354S	0.999
7:102944341:T:C	C354R	0.999
7:102944342:G:A	C354Y	0.999
7:102944342:G:C	C354S	0.999
7:102944413:T:C	C378R	0.999
7:102934112:T:C	C67R	0.998
7:102934185:A:T	N91I	0.998
7:102934186:C:A	N91K	0.998
7:102934186:C:G	N91K	0.998
7:102934248:T:A	L112Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000007686 (7:102922871 A>G), RS1000178607 (7:102929267 C>A,T), RS1000196679 (7:102936358 T>C), RS1000360631 (7:102915900 A>G), RS1000376502 (7:102944038 T>C), RS1000412969 (7:102915737 A>C), RS1000478541 (7:102944476 G>A), RS1000518726 (7:102927272 A>C), RS1000609223 (7:102943931 TG>T), RS1000632351 (7:102928955 G>A), RS1000974464 (7:102927608 C>T), RS1001180616 (7:102923860 A>T), RS1001189341 (7:102936517 C>T), RS1001212399 (7:102942398 C>T), RS1001350935 (7:102917497 T>C)

Disease associations

OMIM: gene MIM:618749 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006479_111	Diverticular disease	4.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	7
trichostatin A	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
methylmercuric chloride	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Nickel	decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
o,p’-DDT	decreases expression	1
boron nitride	decreases expression	1
ferrous chloride	decreases expression	1
1-nitropyrene	decreases expression	1
beta-methylcholine	affects expression	1
phenethyl isothiocyanate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	decreases expression	1
Temozolomide	decreases expression	1
Ketoconazole	decreases expression	1
Lead	increases expression	1
Methotrexate	increases expression	1
Quercetin	affects expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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