LRRC52

Summary

LRRC52 (leucine rich repeat containing 52, HGNC:32156) is a protein-coding gene on chromosome 1q24.1, encoding Leucine-rich repeat-containing protein 52 (Q8N7C0). Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha).

Enables potassium channel activator activity; transmembrane transporter binding activity; and voltage-gated potassium channel activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Part of voltage-gated potassium channel complex.

Source: NCBI Gene 440699 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001005214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32156
Approved symbol	LRRC52
Name	leucine rich repeat containing 52
Location	1q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25811
Ensembl gene	ENSG00000162763
Ensembl biotype	protein_coding
OMIM	615218
Entrez	440699

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000294818

RefSeq mRNA: 1 — MANE Select: NM_001005214 NM_001005214

CCDS: CCDS30930

Canonical transcript exons

ENST00000294818 — 2 exons

Exon	Start	End
ENSE00001068379	165563505	165563957
ENSE00001068380	165544000	165544918

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 88.21.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0411 / max 40.1466, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6389	0.0234	3
6390	0.0150	3
6388	0.0027	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.21	gold quality
left testis	UBERON:0004533	79.10	gold quality
right testis	UBERON:0004534	77.91	gold quality
testis	UBERON:0000473	76.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	66.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	59.46	gold quality
biceps brachii	UBERON:0001507	57.29	gold quality
mucosa of paranasal sinus	UBERON:0005030	57.24	gold quality
nasal cavity epithelium	UBERON:0005384	52.11	gold quality
upper leg skin	UBERON:0004262	51.83	silver quality
muscle of leg	UBERON:0001383	51.18	gold quality
skeletal muscle tissue	UBERON:0001134	51.08	gold quality
gastrocnemius	UBERON:0001388	49.89	gold quality
adult organism	UBERON:0007023	49.13	silver quality
lateral nuclear group of thalamus	UBERON:0002736	49.00	gold quality
Brodmann (1909) area 46	UBERON:0006483	48.42	gold quality
muscle tissue	UBERON:0002385	47.92	gold quality
vastus lateralis	UBERON:0001379	47.39	gold quality
quadriceps femoris	UBERON:0001377	47.22	gold quality
heart left ventricle	UBERON:0002084	46.04	gold quality
cardiac ventricle	UBERON:0002082	45.95	gold quality
lateral globus pallidus	UBERON:0002476	44.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
subthalamic nucleus	UBERON:0001906	42.70	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
renal medulla	UBERON:0000362	42.54	gold quality
trachea	UBERON:0003126	42.46	gold quality
epithelium of nasopharynx	UBERON:0001951	42.20	gold quality
dorsal plus ventral thalamus	UBERON:0001897	42.19	gold quality
substantia nigra pars compacta	UBERON:0001965	41.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting LRRC52, 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-6825-5P	99.96	69.81	3431
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-2277-3P	91.94	62.27	299

Literature-anchored findings (GeneRIF, showing 2)

• Suggest that BK channel modulation by auxiliary gamma subunits depends on intra- and/or juxta-membrane mechanisms. (PMID:26009545)
• LRRC52 is likely a functional component of human KSperdagger. (PMID:38267364)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc52	ENSDARG00000090698
danio_rerio		ENSDARG00000099937
mus_musculus	Lrrc52	ENSMUSG00000040485
rattus_norvegicus	Lrrc52	ENSRNOG00000004356
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), CHAD (ENSG00000136457), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LRIT1 (ENSG00000148602), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), ELFN2 (ENSG00000166897), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), CPN2 (ENSG00000178772), LRIT3 (ENSG00000183423), LRRC26 (ENSG00000184709), LRIG2 (ENSG00000198799), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 52 — Q8N7C0 (reviewed: Q8N7C0)

Alternative names: BK channel auxiliary gamma subunit LRRC52

All UniProt accessions (1): Q8N7C0

UniProt curated annotations — full annotation on UniProt →

Function. Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Modulates gating properties by producing a marked shift in the BK channel’s voltage dependence of activation in the hyperpolarizing direction, and in the absence of calcium. KCNU1 channel auxiliary protein. Modulates KCNU1 gating properties.

Subunit / interactions. May interact with KCNU1; this interaction may be required for LRRC52 stability and may change the channel gating properties. Interacts with KCNMA1.

Subcellular location. Cell membrane.

Tissue specificity. Mainly expressed in testis and skeletal muscle.

Post-translational modifications. N-glycosylated.

Domain organisation. The transmembrane domain is necessary for interaction with KCNMA1.

RefSeq proteins (1): NP_001005214* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR051432	KCNMA1_auxiliary	Family

Pfam: PF13855

UniProt features (22 total): repeat 5, glycosylation site 4, disulfide bond 4, domain 2, topological domain 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N7C0-F1	87.22	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (4): 26–32, 30–39, 188–214, 190–236

Glycosylation sites (4): 112, 148, 189, 211

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9659379	Sensory processing of sound
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 61 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOCC_POTASSIUM_CHANNEL_COMPLEX, GOCC_CATION_CHANNEL_COMPLEX, GOCC_TRANSPORTER_COMPLEX

GO Biological Process (6): establishment of localization in cell (GO:0051649), potassium ion transmembrane transport (GO:0071805), positive regulation of voltage-gated potassium channel activity (GO:1903818), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (5): voltage-gated potassium channel activity (GO:0005249), transmembrane transporter binding (GO:0044325), potassium channel activator activity (GO:0099104), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sensory processing of sound	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
potassium channel activity	2
establishment of localization	1
cellular localization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
voltage-gated potassium channel activity	1
positive regulation of cation channel activity	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
voltage-gated monoatomic cation channel activity	1
protein binding	1
potassium channel regulator activity	1
channel activator activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC52	KCNU1	A8MYU2	915
LRRC52	KCNMB1	P78475	729
LRRC52	KCNMA1	Q12791	621
LRRC52	CATSPER1	Q8NEC5	555
LRRC52	KCNMB4	Q86W47	535
LRRC52	POGK	Q9P215	513
LRRC52	LRRC26	Q2I0M4	502
LRRC52	MGST3	O14880	490
LRRC52	UCK2	Q9BZX2	490
LRRC52	KCNMB3	Q9NPA1	479
LRRC52	EFCAB9	A8MZ26	455
LRRC52	CCDC116	Q8IYX3	450
LRRC52	LRRC10	Q5BKY1	448
LRRC52	ILDR1	Q86SU0	447
LRRC52	TMCO1	Q9UM00	440

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MEOX2	LRRC52	psi-mi:“MI:0915”(physical association)	0.560
M		psi-mi:“MI:0914”(association)	0.350
OR10A4	LRRC73	psi-mi:“MI:0914”(association)	0.350
LRRC52	CANX	psi-mi:“MI:0914”(association)	0.350
LRRC52	DYSF	psi-mi:“MI:0914”(association)	0.350
LRRC52	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): LRRC52 (Biochemical Activity), LRRC52 (Two-hybrid), CANX (Affinity Capture-MS), FAM69A (Affinity Capture-MS), CTAGE5 (Affinity Capture-MS), FAM3C (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), FAM69B (Affinity Capture-MS), LRRC52 (Affinity Capture-MS), NRN1 (Affinity Capture-MS), EFNB1 (Affinity Capture-MS), TPCN1 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), ZDHHC6 (Affinity Capture-MS), CD151 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A2ARI4, A4IIW9, B0BLW3, B1H234, D3ZAL8, D3ZTV3, D4A6D8, D4A7P2, D4AC13, E5DHB5, E7FE13, F1MLX5, F1MT22, F1NUK7, F7D3V9, O43155, O43300, O75473, P0DM44, P21463, P47750, P56495, Q27987, Q3UVD5, Q5R6B1, Q5R6T0, Q5RDJ4, Q66HV9, Q6RKD8, Q80ZD7, Q80ZD8, Q86UE6, Q86VH5, Q86WK6, Q8BGA3, Q8BGT1, Q8BLU0, Q8BZ81, Q8K377

Diamond homologs: A3KNN3, A6H789, A6H793, A6NJW4, A8WHP9, E7FE13, F1MLX5, G5EFX6, O02678, O02833, O35367, O46378, O46379, O46542, O60938, O62702, O75093, O75094, O88279, O88280, O94813, P07359, P07585, P21793, P24014, P28654, P28675, P35858, P35859, P51884, P51885, P51886, P51888, P51890, P58874, P59034, P59035, P70186, P70389, P83286

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

369 predictions. Top by Δscore:

Variant	Effect	Δscore
1:165544854:G:GT	donor_gain	0.9900
1:165563499:TCTTA:T	acceptor_loss	0.9800
1:165563500:CTTAG:C	acceptor_loss	0.9800
1:165563501:TTA:T	acceptor_loss	0.9800
1:165563502:TAGAT:T	acceptor_loss	0.9800
1:165563503:A:AG	acceptor_gain	0.9800
1:165563503:A:C	acceptor_loss	0.9800
1:165563503:AGAT:A	acceptor_gain	0.9800
1:165563504:G:GG	acceptor_gain	0.9800
1:165563504:GAT:G	acceptor_gain	0.9800
1:165563504:GATG:G	acceptor_gain	0.9800
1:165544914:CTCAG:C	donor_loss	0.9600
1:165544915:TCAG:T	donor_loss	0.9600
1:165544916:CAG:C	donor_loss	0.9600
1:165544917:AG:A	donor_loss	0.9600
1:165544918:GGTGA:G	donor_loss	0.9600
1:165544920:T:G	donor_loss	0.9600
1:165562833:G:GT	donor_gain	0.9300
1:165545929:G:A	acceptor_gain	0.9200
1:165563504:GA:G	acceptor_gain	0.9000
1:165563526:TGGAG:T	acceptor_gain	0.9000
1:165544854:G:T	donor_gain	0.8900
1:165545113:C:G	donor_gain	0.8900
1:165563166:T:TA	acceptor_gain	0.8900
1:165544921:GAGG:G	donor_loss	0.8500
1:165544112:GGCAT:G	donor_gain	0.7800
1:165562215:G:GT	donor_gain	0.7700
1:165563527:GGAG:G	acceptor_gain	0.7500
1:165563490:T:TA	acceptor_loss	0.7200
1:165563504:GATGA:G	acceptor_gain	0.7100

AlphaMissense

2043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:165544469:T:C	L58P	0.998
1:165544613:T:C	L106P	0.998
1:165544685:T:C	L130P	0.998
1:165544852:T:A	W186R	0.998
1:165544852:T:C	W186R	0.998
1:165544854:G:C	W186C	0.998
1:165544854:G:T	W186C	0.998
1:165544532:T:A	L79H	0.997
1:165544619:T:C	L108P	0.997
1:165544858:T:A	C188S	0.997
1:165544859:G:C	C188S	0.997
1:165563522:T:A	C214S	0.997
1:165563523:G:A	C214Y	0.997
1:165563523:G:C	C214S	0.997
1:165563524:T:G	C214W	0.997
1:165544411:T:A	C39S	0.996
1:165544411:T:C	C39R	0.996
1:165544412:G:C	C39S	0.996
1:165544413:C:G	C39W	0.996
1:165544541:T:C	L82S	0.996
1:165544546:T:C	C84R	0.996
1:165544604:T:A	L103H	0.996
1:165544628:A:T	N111I	0.996
1:165544858:T:C	C188R	0.996
1:165563522:T:C	C214R	0.996
1:165544532:T:C	L79P	0.995
1:165544613:T:A	L106H	0.995
1:165544760:T:C	L155P	0.995
1:165544859:G:A	C188Y	0.995
1:165544860:C:G	C188W	0.995

dbSNP variants (sampled 300 via entrez): RS1000042435 (1:165558913 C>T), RS1000052492 (1:165548041 G>A), RS1000160561 (1:165542203 T>C), RS1000241480 (1:165548532 G>A), RS1000388286 (1:165542229 A>G), RS1000568833 (1:165554183 A>C,G), RS1000633936 (1:165554698 G>A,T), RS1000663435 (1:165554409 C>A), RS1000958045 (1:165560045 T>C), RS1001162909 (1:165559640 T>C), RS1001179724 (1:165548352 G>A), RS1001303589 (1:165559433 A>G), RS1001558966 (1:165561400 G>C,T), RS1001572477 (1:165555416 G>A), RS1001646380 (1:165550173 T>C)

Disease associations

OMIM: gene MIM:615218 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Plant Extracts	decreases expression, affects cotreatment	1
Antirheumatic Agents	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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