LRRC38

Summary

LRRC38 (leucine rich repeat containing 38, HGNC:27005) is a protein-coding gene on chromosome 1p36.21, encoding Leucine-rich repeat-containing protein 38 (Q5VT99). Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha).

Enables potassium channel activator activity and transmembrane transporter binding 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 126755 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_001010847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27005
Approved symbol	LRRC38
Name	leucine rich repeat containing 38
Location	1p36.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162494
Ensembl biotype	protein_coding
OMIM	615212
Entrez	126755

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000376085

RefSeq mRNA: 1 — MANE Select: NM_001010847 NM_001010847

CCDS: CCDS53269

Canonical transcript exons

ENST00000376085 — 2 exons

Exon	Start	End
ENSE00001065769	13512963	13514003
ENSE00001917748	13474973	13476099

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 88.23.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2442 / max 781.7204, expressed in 188 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10415	0.8400	115
10409	0.6025	61
10411	0.4645	74
10414	0.1811	40
10412	0.1007	26
10410	0.0416	10
10413	0.0139	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	88.23	gold quality
muscle of leg	UBERON:0001383	86.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.31	gold quality
right adrenal gland	UBERON:0001233	82.44	gold quality
right adrenal gland cortex	UBERON:0035827	81.90	gold quality
left adrenal gland	UBERON:0001234	81.87	gold quality
left adrenal gland cortex	UBERON:0035825	81.65	gold quality
adrenal cortex	UBERON:0001235	79.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.58	gold quality
adrenal gland	UBERON:0002369	77.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.07	gold quality
cerebellar cortex	UBERON:0002129	67.04	gold quality
cerebellar hemisphere	UBERON:0002245	66.85	gold quality
lower esophagus mucosa	UBERON:0035834	66.78	gold quality
cerebellum	UBERON:0002037	65.37	gold quality
prefrontal cortex	UBERON:0000451	61.81	gold quality
adrenal tissue	UBERON:0018303	61.60	gold quality
lower lobe of lung	UBERON:0008949	59.83	silver quality
skeletal muscle tissue	UBERON:0001134	57.44	gold quality
right frontal lobe	UBERON:0002810	56.26	gold quality
frontal cortex	UBERON:0001870	56.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	56.00	gold quality
neocortex	UBERON:0001950	55.27	gold quality
anterior cingulate cortex	UBERON:0009835	55.04	gold quality
primary visual cortex	UBERON:0002436	54.83	gold quality
tendon of biceps brachii	UBERON:0008188	54.69	gold quality
muscle tissue	UBERON:0002385	54.67	gold quality
skin of abdomen	UBERON:0001416	54.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	53.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting LRRC38, 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-150-5P	99.99	66.69	1976
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-940	99.37	66.14	2064

Literature-anchored findings (GeneRIF, showing 1)

• Suggest that BK channel modulation by auxiliary gamma subunits depends on intra- and/or juxta-membrane mechanisms. (PMID:26009545)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc38a	ENSDARG00000075147
mus_musculus	Lrrc38	ENSMUSG00000028584
rattus_norvegicus	Lrrc38	ENSRNOG00000015264

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), SLITRK1 (ENSG00000178235), GP5 (ENSG00000178732), SLITRK4 (ENSG00000179542), LRRC55 (ENSG00000183908), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 38 — Q5VT99 (reviewed: Q5VT99)

Alternative names: BK channel auxiliary gamma subunit LRRC38

All UniProt accessions (1): Q5VT99

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 adrenal gland, thymus and skeletal muscle.

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

RefSeq proteins (1): NP_001010847* (*=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
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF13855

UniProt features (16 total): repeat 5, disulfide bond 4, sequence variant 2, 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-Q5VT99-F1	86.59	0.63

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): 28–34, 32–42, 190–217, 192–239

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (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 (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

548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC38	KCNMB1	P78475	734
LRRC38	KCNU1	A8MYU2	584
LRRC38	LRRC26	Q2I0M4	565
LRRC38	TCEANC2	Q96MN5	523
LRRC38	KCNMA1	Q12791	511
LRRC38	KCNMB3	Q9NPA1	505
LRRC38	KCNMB4	Q86W47	492
LRRC38	HDHD5	Q9BXW7	491
LRRC38	LRRC30	A6NM36	488
LRRC38	TMEM132C	Q8N3T6	475
LRRC38	LRRC14B	A6NHZ5	465
LRRC38	LRRC20	Q8TCA0	465
LRRC38	PRAMEF8	Q5VWM4	447
LRRC38	INPP5J	Q15735	444
LRRC38	ASB12	Q8WXK4	436

IntAct

0 interactions, top by confidence:

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, A4IFA6, A6H793, A6NJW4, B1H234, F1NUK7, G5EG78, O14498, O15335, O55226, O70210, O75093, O75325, O88186, O88279, O94813, P14770, P59034, P59035, P70193, Q27972, Q2I0M4, Q3V1M1, Q5NVQ6, Q5R6T0, Q5RAC4, Q6GU68, Q6NUI6, Q6RKD8, Q6WRH9, Q6WRI0, Q80TR4, Q80WD1, Q810B8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

474 predictions. Top by Δscore:

Variant	Effect	Δscore
1:13476100:C:CC	acceptor_gain	1.0000
1:13512958:CTCA:C	donor_loss	1.0000
1:13512959:TCA:T	donor_loss	1.0000
1:13512960:CAC:C	donor_loss	1.0000
1:13476096:AGGC:A	acceptor_gain	0.9900
1:13476098:GC:G	acceptor_gain	0.9900
1:13476099:CC:C	acceptor_gain	0.9900
1:13476100:C:CG	acceptor_loss	0.9900
1:13476112:A:T	acceptor_gain	0.9900
1:13497625:A:C	acceptor_gain	0.9900
1:13498034:T:C	donor_gain	0.9900
1:13512957:GCTCA:G	donor_loss	0.9900
1:13512961:AC:A	donor_gain	0.9900
1:13512962:CC:C	donor_gain	0.9900
1:13476095:AAGGC:A	acceptor_gain	0.9800
1:13476097:GGC:G	acceptor_gain	0.9800
1:13476111:C:CT	acceptor_gain	0.9800
1:13476115:C:CT	acceptor_gain	0.9800
1:13494721:G:A	donor_gain	0.9800
1:13512961:A:AC	donor_gain	0.9800
1:13512962:C:CC	donor_gain	0.9800
1:13512962:CCT:C	donor_gain	0.9800
1:13476100:C:T	acceptor_gain	0.9700
1:13512962:CCTT:C	donor_gain	0.9700
1:13476098:GCCT:G	acceptor_gain	0.9600
1:13476116:A:T	acceptor_gain	0.9600
1:13508707:T:TG	acceptor_gain	0.9600
1:13476097:GGCCT:G	acceptor_gain	0.9500
1:13497625:A:AC	acceptor_gain	0.9500
1:13476099:CCTG:C	acceptor_gain	0.9400

AlphaMissense

1918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:13513030:C:A	W188C	0.998
1:13513030:C:G	W188C	0.998
1:13513032:A:G	W188R	0.998
1:13513032:A:T	W188R	0.998
1:13513252:G:C	N114K	0.998
1:13513252:G:T	N114K	0.998
1:13513253:T:A	N114I	0.998
1:13513324:G:C	N90K	0.998
1:13513324:G:T	N90K	0.998
1:13475933:G:C	S266R	0.997
1:13475933:G:T	S266R	0.997
1:13475935:T:G	S266R	0.997
1:13513118:A:G	L159P	0.997
1:13513118:A:T	L159H	0.997
1:13513124:A:G	L157P	0.997
1:13513180:G:C	N138K	0.997
1:13513180:G:T	N138K	0.997
1:13513182:T:A	N138Y	0.997
1:13513196:A:G	L133P	0.997
1:13513196:A:T	L133H	0.997
1:13513254:T:A	N114Y	0.997
1:13513262:A:G	L111P	0.997
1:13476081:C:G	C217S	0.996
1:13476082:A:T	C217S	0.996
1:13513025:C:G	C190S	0.996
1:13513025:C:T	C190Y	0.996
1:13513026:A:T	C190S	0.996
1:13513036:G:C	N186K	0.996
1:13513036:G:T	N186K	0.996
1:13513038:T:C	N186D	0.996

dbSNP variants (sampled 300 via entrez): RS1000036881 (1:13495116 G>A), RS1000124161 (1:13474788 G>C), RS1000145031 (1:13500701 A>C), RS1000367784 (1:13503291 C>G,T), RS1000396002 (1:13488168 A>G), RS1000565462 (1:13505347 A>G), RS1000576809 (1:13505172 C>G,T), RS1000613086 (1:13515919 A>C), RS1000660721 (1:13480485 T>C), RS1000706988 (1:13481938 T>G), RS1000746074 (1:13475171 T>C), RS1000831895 (1:13487033 C>T), RS1000834853 (1:13489214 C>T), RS1001004788 (1:13498253 A>C), RS1001037406 (1:13493819 C>T)

Disease associations

OMIM: gene MIM:615212 | 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
GCST002938_8	Copper levels	7.000000e-07
GCST010002_352	Refractive error	2.000000e-09

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
Doxorubicin	increases expression	2
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Cadmium	increases abundance, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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