LRRC55

Summary

LRRC55 (leucine rich repeat containing 55, HGNC:32324) is a protein-coding gene on chromosome 11q12.1, encoding Leucine-rich repeat-containing protein 55 (Q6ZSA7). 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 219527 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001005210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32324
Approved symbol	LRRC55
Name	leucine rich repeat containing 55
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45686
Ensembl gene	ENSG00000183908
Ensembl biotype	protein_coding
OMIM	615213
Entrez	219527

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000497933, ENST00000652194

RefSeq mRNA: 1 — MANE Select: NM_001005210 NM_001005210

CCDS: CCDS31539

Canonical transcript exons

ENST00000497933 — 2 exons

Exon	Start	End
ENSE00001932289	57187245	57191717
ENSE00003894871	57181953	57182683

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 92.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1404 / max 16.4399, expressed in 57 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114253	0.1404	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	92.86	gold quality
cortical plate	UBERON:0005343	91.92	gold quality
ventricular zone	UBERON:0003053	74.37	gold quality
prefrontal cortex	UBERON:0000451	71.96	gold quality
endothelial cell	CL:0000115	71.38	silver quality
hypothalamus	UBERON:0001898	68.56	gold quality
left ventricle myocardium	UBERON:0006566	66.55	gold quality
frontal cortex	UBERON:0001870	66.46	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.22	gold quality
neocortex	UBERON:0001950	66.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.89	gold quality
substantia nigra	UBERON:0002038	65.25	gold quality
midbrain	UBERON:0001891	64.52	gold quality
right frontal lobe	UBERON:0002810	64.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	63.68	gold quality
kidney epithelium	UBERON:0004819	63.64	gold quality
upper arm skin	UBERON:0004263	63.26	gold quality
cerebral cortex	UBERON:0000956	63.12	gold quality
primary visual cortex	UBERON:0002436	62.58	gold quality
anterior cingulate cortex	UBERON:0009835	62.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	61.61	gold quality
lymph node	UBERON:0000029	61.36	gold quality
spinal cord	UBERON:0002240	61.18	gold quality
occipital lobe	UBERON:0002021	60.94	gold quality
smooth muscle tissue	UBERON:0001135	60.55	gold quality
vermiform appendix	UBERON:0001154	59.31	gold quality
colonic epithelium	UBERON:0000397	58.93	gold quality
forebrain	UBERON:0001890	58.06	gold quality
amygdala	UBERON:0001876	57.75	gold quality
substantia nigra pars reticulata	UBERON:0001966	57.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

146 targeting LRRC55, 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-4795-3P	100.00	74.62	4024
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 3)

• Suggest that BK channel modulation by auxiliary gamma subunits depends on intra- and/or juxta-membrane mechanisms. (PMID:26009545)
• Interferon-inducible cytoplasmic lncLrrc55-AS promotes antiviral innate responses by strengthening IRF3 phosphorylation. (PMID:31213650)
• Upregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes. (PMID:33346797)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc55	ENSMUSG00000075224
rattus_norvegicus	Lrrc55	ENSRNOG00000028266

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), SLITRK1 (ENSG00000178235), GP5 (ENSG00000178732), SLITRK4 (ENSG00000179542), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 55 — Q6ZSA7 (reviewed: Q6ZSA7)

Alternative names: BK channel auxiliary gamma subunit LRRC55

All UniProt accessions (2): Q6ZSA7, A0A494C0H1

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.

Subunit / interactions. Interacts with KCNMA1.

Subcellular location. Cell membrane.

Tissue specificity. Mainly expressed in brain.

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

RefSeq proteins (1): NP_001005210* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
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
IPR051432	KCNMA1_auxiliary	Family

Pfam: PF13855

UniProt features (14 total): repeat 5, disulfide bond 4, domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZSA7-F1	86.80	0.67

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): 38–44, 42–51, 200–227, 202–249

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, 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

GO Biological Process (4): potassium ion transmembrane transport (GO:0071805), positive regulation of voltage-gated potassium channel activity (GO:1903818), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (4): voltage-gated potassium channel activity (GO:0005249), transmembrane transporter binding (GO:0044325), potassium channel activator activity (GO:0099104), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
potassium channel activity	2
potassium ion transport	1
monoatomic cation transmembrane transport	1
voltage-gated potassium channel activity	1
positive regulation of cation channel activity	1
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
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

746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC55	KCNMB1	P78475	720
LRRC55	KCNU1	A8MYU2	535
LRRC55	KCNMA1	Q12791	501
LRRC55	KCNMB3	Q9NPA1	475
LRRC55	KCNMB4	Q86W47	461
LRRC55	LRRC26	Q2I0M4	409
LRRC55	SLC6A18	Q96N87	397
LRRC55	CTXN2	P0C2S0	393
LRRC55	STUM	Q69YW2	390
LRRC55	LRRC10	Q5BKY1	379
LRRC55	OR5W2	Q8NH69	369
LRRC55	LRRC58	Q96CX6	365
LRRC55	OR5D13	Q8NGL4	353
LRRC55	PPME1	Q9Y570	349
LRRC55	OR5AR1	Q8NGP9	349

IntAct

2 interactions, top by confidence:

A	B	Type	Score
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): SLC16A10 (Affinity Capture-MS), LETMD1 (Affinity Capture-MS), SLC47A1 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), MTCH1 (Affinity Capture-MS), TMEM183A (Affinity Capture-MS), TMEM219 (Affinity Capture-MS), SLC9A1 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), FZD6 (Affinity Capture-MS), TMEM194A (Affinity Capture-MS), ZDHHC9 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), B4GALNT3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A2ARI4, A2VDH3, A6H793, D4A6D8, E9Q7T7, F1MLX5, F1MT22, O75325, P59034, P59035, Q13641, Q149C3, Q3URE9, Q3UVD5, Q3UY51, Q4KLL3, Q4R8Y9, Q50LG9, Q5M8M9, Q5PQV5, Q5R6B1, Q5RDJ4, Q5VT99, Q6GQU6, Q6UY18, Q6ZSA7, Q7M6Z0, Q7TQ62, Q80WD1, Q86UE6, Q86UN2, Q86UN3, Q86WK6, Q8BHA1, Q8K0S5, Q8K377, Q8N7C0, Q91ZV8, Q96FE5

Diamond homologs: A2VDH3, O88280, Q13641, Q3UY51, Q4KLL3, Q5VT99, Q6ZSA7, A2ARI4, A3KNN3, A4IFA6, A6H789, A6H793, A6NJW4, A8WHP9, D4AC13, E5DHB5, E7FE13, F1MLX5, F1MT22, F7D3V9, G5EFX6, O00206, O02833, O14498, O35367, O35930, O46378, O46379, O46542, O62702, O75093, O75473, O88279, O94769, O94898, P07359, P07585, P0DKB5, P0DM44, P21793

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

293 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57182680:GCAG:G	donor_gain	1.0000
11:57182681:CAGG:C	donor_loss	1.0000
11:57182682:AGGT:A	donor_loss	1.0000
11:57182684:G:GA	donor_loss	1.0000
11:57187469:G:GT	donor_gain	1.0000
11:57183695:GCCC:G	donor_gain	0.9700
11:57182681:C:T	donor_gain	0.9600
11:57182670:GCGCT:G	donor_gain	0.9500
11:57182684:G:GG	donor_gain	0.9500
11:57187243:A:AG	acceptor_gain	0.9400
11:57187244:G:GG	acceptor_gain	0.9400
11:57187458:C:T	donor_gain	0.9400
11:57187235:T:A	acceptor_loss	0.9200
11:57187238:GTTAC:G	acceptor_loss	0.9200
11:57187239:TTACA:T	acceptor_loss	0.9200
11:57187240:TACA:T	acceptor_loss	0.9200
11:57187241:ACAG:A	acceptor_loss	0.9200
11:57187242:C:CG	acceptor_loss	0.9200
11:57187243:AGAT:A	acceptor_loss	0.9200
11:57187593:TTC:T	donor_gain	0.9200
11:57183705:GT:G	donor_gain	0.7900
11:57187236:GTGTT:G	acceptor_loss	0.7500
11:57187470:A:T	donor_gain	0.7500
11:57182425:G:GT	donor_gain	0.7400
11:57183664:C:G	donor_gain	0.7400
11:57184326:G:GC	acceptor_gain	0.7100
11:57183415:A:AG	acceptor_gain	0.6900
11:57183416:G:GG	acceptor_gain	0.6900
11:57183416:GAA:G	acceptor_gain	0.6900
11:57191156:CTAG:C	acceptor_gain	0.6900

AlphaMissense

1949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57187262:T:A	C227S	0.999
11:57187263:G:C	C227S	0.999
11:57187395:C:A	A271D	0.999
11:57182246:A:T	N75I	0.998
11:57182614:T:A	W198R	0.998
11:57182614:T:C	W198R	0.998
11:57182616:G:C	W198C	0.998
11:57182616:G:T	W198C	0.998
11:57182621:G:A	C200Y	0.998
11:57187376:G:C	G265R	0.998
11:57187377:G:A	G265D	0.998
11:57187404:C:A	A274D	0.998
11:57187411:C:A	N276K	0.998
11:57187411:C:G	N276K	0.998
11:57182173:T:A	C51S	0.997
11:57182174:G:C	C51S	0.997
11:57182175:T:G	C51W	0.997
11:57182231:T:C	L70P	0.997
11:57182390:A:T	N123I	0.997
11:57182391:C:A	N123K	0.997
11:57182391:C:G	N123K	0.997
11:57182463:C:A	N147K	0.997
11:57182463:C:G	N147K	0.997
11:57182620:T:A	C200S	0.997
11:57182620:T:C	C200R	0.997
11:57182621:G:C	C200S	0.997
11:57187262:T:C	C227R	0.997
11:57187386:T:A	V268D	0.997
11:57182174:G:A	C51Y	0.996
11:57182245:A:T	N75Y	0.996

dbSNP variants (sampled 300 via entrez): RS1000425909 (11:57182792 T>C), RS1000638071 (11:57191460 C>T), RS1001060060 (11:57187086 A>G), RS1001092577 (11:57185887 A>T), RS1001125180 (11:57185594 C>T), RS1001468011 (11:57191764 A>G), RS1001728786 (11:57189702 T>C), RS1002139966 (11:57184741 G>C,T), RS1002326917 (11:57189982 C>A), RS1002430325 (11:57191369 T>G), RS1002760688 (11:57186968 T>C), RS1002775004 (11:57190747 G>A), RS1003136006 (11:57188309 G>A,T), RS1003151597 (11:57180696 G>A,T), RS1003430329 (11:57189933 T>C)

Disease associations

OMIM: gene MIM:615213 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006107_12	Upper eyelid morphology	3.000000e-06
GCST010242_392	HDL cholesterol levels	5.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	4
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
bisphenol A	increases methylation	1
trichostatin A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Allergens	decreases expression	1
Niclosamide	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YA73	IDG-HEK293T-LRRC55-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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