LRRC66

Summary

LRRC66 (leucine rich repeat containing 66, HGNC:34299) is a protein-coding gene on chromosome 4q12, encoding Leucine-rich repeat-containing protein 66 (Q68CR7).

This gene encodes a protein belonging to the leucine-rich repeat family of proteins, which are involved in diverse biological processes, including cell adhesion, cellular trafficking, and hormone-receptor interactions.

Source: NCBI Gene 339977 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 143 total
• MANE Select transcript: NM_001024611

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34299
Approved symbol	LRRC66
Name	leucine rich repeat containing 66
Location	4q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188993
Ensembl biotype	protein_coding
Entrez	339977

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000343457, ENST00000682860, ENST00000893845, ENST00000893846, ENST00000893847

RefSeq mRNA: 1 — MANE Select: NM_001024611 NM_001024611

CCDS: CCDS43229

Canonical transcript exons

ENST00000682860 — 5 exons

Exon	Start	End
ENSE00001380621	51997748	51997937
ENSE00001384752	52003223	52003392
ENSE00003916095	52017118	52017618
ENSE00003918712	52020304	52020363
ENSE00003919543	51993652	51996165

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 90.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0983 / max 62.4687, expressed in 23 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52098	0.0509	10
52099	0.0474	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	90.30	gold quality
duodenum	UBERON:0002114	86.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.31	gold quality
jejunum	UBERON:0002115	78.17	gold quality
colonic mucosa	UBERON:0000317	76.59	gold quality
rectum	UBERON:0001052	76.02	gold quality
gastrocnemius	UBERON:0001388	75.67	gold quality
mucosa of transverse colon	UBERON:0004991	75.47	gold quality
muscle of leg	UBERON:0001383	75.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	74.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.45	gold quality
small intestine	UBERON:0002108	72.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	71.41	gold quality
deltoid	UBERON:0001476	70.38	gold quality
skeletal muscle tissue	UBERON:0001134	67.28	gold quality
transverse colon	UBERON:0001157	66.86	gold quality
intestine	UBERON:0000160	66.80	gold quality
muscle tissue	UBERON:0002385	66.30	gold quality
vastus lateralis	UBERON:0001379	65.38	gold quality
quadriceps femoris	UBERON:0001377	65.26	gold quality
large intestine	UBERON:0000059	64.92	gold quality
gall bladder	UBERON:0002110	64.73	gold quality
colon	UBERON:0001155	64.56	gold quality
adenohypophysis	UBERON:0002196	64.04	gold quality
islet of Langerhans	UBERON:0000006	63.17	gold quality
pituitary gland	UBERON:0000007	61.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.95	gold quality
smooth muscle tissue	UBERON:0001135	60.70	gold quality
biceps brachii	UBERON:0001507	60.34	silver quality
apex of heart	UBERON:0002098	60.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting LRRC66, 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-6867-5P	100.00	82.21	3464
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-130A-5P	99.33	70.26	2623

Literature-anchored findings (GeneRIF, showing 1)

• Polymorphisms in the HSF2, LRRC6, MEIG1 and PTIP genes correlate with sperm motility in idiopathic infertility. (PMID:35768906)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc66	ENSMUSG00000067206
rattus_norvegicus	Lrrc66	ENSRNOG00000026585

Paralogs (22): DCN (ENSG00000011465), RTN4R (ENSG00000040608), ASPN (ENSG00000106819), FLRT3 (ENSG00000125848), FLRT1 (ENSG00000126500), LRRC4 (ENSG00000128594), LRRC4B (ENSG00000131409), PODNL1 (ENSG00000132000), LRTM1 (ENSG00000144771), LRRC4C (ENSG00000148948), LRRTM1 (ENSG00000162951), LRRC15 (ENSG00000172061), PODN (ENSG00000174348), LRRTM4 (ENSG00000176204), BGN (ENSG00000182492), LRRC19 (ENSG00000184434), FLRT2 (ENSG00000185070), GP1BA (ENSG00000185245), RTN4RL1 (ENSG00000185924), RTN4RL2 (ENSG00000186907), NYX (ENSG00000188937), LRRTM3 (ENSG00000198739)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 66 — Q68CR7 (reviewed: Q68CR7)

All UniProt accessions (1): Q68CR7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001019782* (*=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: PF00560, PF13855

UniProt features (28 total): compositionally biased region 7, repeat 6, region of interest 5, glycosylation site 4, transmembrane region 2, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68CR7-F1	47.32	0.11

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 (2): 723, 752

Glycosylation sites (4): 45, 115, 746, 756

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): ZHENG_BOUND_BY_FOXP3, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, chr4q12, ZWANG_EGF_INTERVAL_UP, ATF5_TARGET_GENES, CREB3L4_TARGET_GENES, DLX2_TARGET_GENES, NKX2_2_TARGET_GENES, ZFHX3_TARGET_GENES, MIR186_5P, MIR4753_3P, MIR130A_5P, MIR130B_5P, MIR6770_5P, MIR4695_3P

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC66	GLOD4	Q9HC38	530
LRRC66	SUSD3	Q96L08	526
LRRC66	CIMIP6	Q8N5S3	506
LRRC66	PDCL2	Q8N4E4	480
LRRC66	DCUN1D4	Q92564	475
LRRC66	NAGLU	P54802	459
LRRC66	CCDC90B	Q9GZT6	458
LRRC66	BEND4	Q6ZU67	457
LRRC66	FAM32A	Q9Y421	452
LRRC66	USP46	P62068	447
LRRC66	ACBD7	Q8N6N7	446
LRRC66	SHISA3	A0PJX4	441
LRRC66	TMEM156	Q8N614	435
LRRC66	NFXL1	Q6ZNB6	418
LRRC66	LRRC27	Q9C0I9	410

IntAct

3 interactions, top by confidence:

A	B	Type	Score
LRRC66	ACOX1	psi-mi:“MI:0915”(physical association)	0.400
APP	LRRC66	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): LRRC66 (Affinity Capture-MS), LRRC66 (Two-hybrid), LRRC66 (Proximity Label-MS)

ESM2 similar proteins: A0A0A6YY25, A0A5K7RLP0, A6NMK8, A8MVX0, B2RQL2, B2RXH4, C9JSJ3, D2J0Y4, O54824, P97303, Q01954, Q05AH6, Q0VET5, Q14005, Q1W617, Q2YDE2, Q3MHT3, Q3U0P1, Q3ULM6, Q3UXL4, Q4R7L6, Q5RC05, Q5T0L3, Q68CR7, Q6GQV1, Q6NS69, Q6NZK5, Q6P1D7, Q6PG16, Q6ZVT6, Q7Z4V0, Q80W88, Q80XI1, Q811R2, Q86T90, Q86YN6, Q8BHP2, Q8BLK9, Q8BP99, Q8BW86

Diamond homologs: A1KZ92, A2AJ76, A2CG49, A4IGL7, A4IIW9, A8WGA3, A8WHP9, B0BNK7, B1H234, D2HFT7, D3YXG0, D3YYU8, D3ZZ80, D4A1J9, D4ABX8, O01761, O15146, O35930, O42414, O55005, O60229, O60602, O75147, O89026, O97394, P0C5H6, P0C6S8, P0C7J6, P11627, P11799, P15209, P20241, P22648, P32004, P43146, P70211, P97924, P98160, Q05695, Q05793

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

587 predictions. Top by Δscore:

Variant	Effect	Δscore
4:51996162:CTCC:C	acceptor_gain	0.9900
4:51996163:TCCC:T	acceptor_loss	0.9900
4:51996164:CC:C	acceptor_gain	0.9900
4:51996165:CC:C	acceptor_gain	0.9900
4:51996165:CCTG:C	acceptor_loss	0.9900
4:51996166:C:CG	acceptor_loss	0.9900
4:51997937:CCT:C	acceptor_loss	0.9900
4:51997938:C:CA	acceptor_loss	0.9900
4:51996161:ACTCC:A	acceptor_gain	0.9800
4:51996162:CTCCC:C	acceptor_gain	0.9800
4:51996163:TCC:T	acceptor_gain	0.9800
4:51996163:TCCCT:T	acceptor_gain	0.9800
4:51996164:CCC:C	acceptor_gain	0.9800
4:51996166:C:CC	acceptor_gain	0.9800
4:51996167:T:A	acceptor_loss	0.9800
4:51997749:TATAG:T	donor_gain	0.9800
4:51997750:ATAGA:A	donor_gain	0.9800
4:51996172:G:C	acceptor_gain	0.9700
4:51996172:G:GC	acceptor_gain	0.9700
4:51996178:T:TC	acceptor_gain	0.9700
4:51997742:ACTT:A	donor_loss	0.9600
4:51997743:CT:C	donor_loss	0.9600
4:51997744:TTACC:T	donor_loss	0.9600
4:51997745:T:TA	donor_loss	0.9600
4:51997746:A:AG	donor_loss	0.9600
4:51997747:C:CA	donor_loss	0.9600
4:51997545:C:CT	acceptor_gain	0.9400
4:51996169:CAAG:C	acceptor_gain	0.9300
4:51997938:C:CC	acceptor_gain	0.9300
4:52017116:AC:A	donor_gain	0.9300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000279653 (4:51993588 G>A), RS1000361763 (4:52012269 T>C), RS1000426744 (4:51993989 T>C,G), RS1000478910 (4:52012612 G>A), RS1000545370 (4:51998561 G>C,T), RS1000705262 (4:52005388 A>G), RS1000765615 (4:51998616 A>C,G), RS1000770131 (4:52005001 TA>T), RS1000837805 (4:52006493 C>A,G), RS1000905614 (4:52011627 A>C), RS1000915388 (4:52011861 A>G), RS1000997248 (4:52005004 A>G), RS1001144502 (4:52019376 TTATCTATC>T,TTATC,TTATCTATCTATC,TTATCTATCTATCTATC), RS1001226313 (4:51994176 T>A), RS1001484508 (4:52019125 T>C)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, decreases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
trichostatin A	decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression, affects cotreatment	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases methylation	1
Asbestos, Serpentine	decreases methylation	1
Cadmium Chloride	decreases expression	1
Palmitic Acid	decreases expression	1
Particulate Matter	decreases expression, increases expression	1

Clinical trials (associated diseases)

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