LRRC23

Summary

LRRC23 (leucine rich repeat containing 23, HGNC:19138) is a protein-coding gene on chromosome 12p13.31, encoding Leucine-rich repeat-containing protein 23 (Q53EV4). Essential for sperm motility and male fertility.

Involved in flagellated sperm motility and radial spoke assembly. Located in cytoplasm and sperm flagellum. Implicated in spermatogenic failure 92.

Source: NCBI Gene 10233 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 92 (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 61 total — 2 pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_001135217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19138
Approved symbol	LRRC23
Name	leucine rich repeat containing 23
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	B7, LRPB7
Ensembl gene	ENSG00000010626
Ensembl biotype	protein_coding
OMIM	620708
Entrez	10233

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000007969, ENST00000323702, ENST00000415834, ENST00000428946, ENST00000429740, ENST00000431207, ENST00000433346, ENST00000436789, ENST00000443597, ENST00000449039, ENST00000451681, ENST00000457146, ENST00000472633, ENST00000486401, ENST00000622489, ENST00000859742, ENST00000859743, ENST00000965134

RefSeq mRNA: 3 — MANE Select: NM_001135217 NM_001135217, NM_006992, NM_201650

CCDS: CCDS8568, CCDS8569

Canonical transcript exons

ENST00000443597 — 8 exons

Exon	Start	End
ENSE00000866978	6905845	6905954
ENSE00001491456	6913891	6914229
ENSE00001616380	6904822	6905075
ENSE00003495095	6912730	6913027
ENSE00003530780	6906409	6906662
ENSE00003544592	6907315	6907445
ENSE00003554069	6905585	6905759
ENSE00003571350	6909890	6910026

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6905 / max 95.6300, expressed in 1684 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123790	4.1644	1621
123788	2.4950	884
123793	0.6330	170
123792	0.5918	207
123791	0.2159	106
123787	0.0853	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.00	gold quality
bronchial epithelial cell	CL:0002328	98.12	gold quality
epithelium of bronchus	UBERON:0002031	97.83	gold quality
bronchus	UBERON:0002185	97.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.21	gold quality
left testis	UBERON:0004533	91.64	gold quality
nasal cavity epithelium	UBERON:0005384	91.52	gold quality
right testis	UBERON:0004534	91.28	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.07	gold quality
testis	UBERON:0000473	89.92	gold quality
caudate nucleus	UBERON:0001873	88.61	gold quality
nucleus accumbens	UBERON:0001882	88.58	gold quality
sural nerve	UBERON:0015488	88.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.46	gold quality
cerebellar hemisphere	UBERON:0002245	88.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.32	gold quality
cerebellar cortex	UBERON:0002129	88.29	gold quality
amygdala	UBERON:0001876	88.13	gold quality
hypothalamus	UBERON:0001898	87.85	gold quality
right frontal lobe	UBERON:0002810	87.44	gold quality
putamen	UBERON:0001874	87.42	gold quality
cingulate cortex	UBERON:0003027	87.07	gold quality
adenohypophysis	UBERON:0002196	86.89	gold quality
anterior cingulate cortex	UBERON:0009835	86.86	gold quality
spinal cord	UBERON:0002240	86.65	gold quality
cerebellum	UBERON:0002037	86.48	gold quality
pituitary gland	UBERON:0000007	86.45	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.20	gold quality
islet of Langerhans	UBERON:0000006	85.87	gold quality
right lung	UBERON:0002167	85.51	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	64.72
E-MTAB-10287	yes	26.44
E-HCAD-1	yes	26.12
E-GEOD-130148	yes	11.40
E-ANND-3	yes	10.79

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes. (PMID:37804054)
• LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility. (PMID:38091523)
• Novel mutations in LRRC23 cause asthenozoospermia in a nonconsanguineous family. (PMID:39054792)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc23	ENSDARG00000006174
mus_musculus	Lrrc23	ENSMUSG00000030125
rattus_norvegicus	Lrrc23	ENSRNOG00000026309
drosophila_melanogaster	TbCMF46	FBGN0032163
drosophila_melanogaster	Ppr-Y	FBGN0046697

Paralogs (13): LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), DNAAF1 (ENSG00000154099), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), DRC3 (ENSG00000171962), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 23 — Q53EV4 (reviewed: Q53EV4)

Alternative names: Leucine-rich protein B7

All UniProt accessions (6): Q53EV4, C9JEW3, C9JKE8, C9JQN5, E9PDZ4, F2Z299

UniProt curated annotations — full annotation on UniProt →

Function. Essential for sperm motility and male fertility. Plays an important role in the proper assembly of the third radial spoke (RS3) head and the bridge structure between RS2 and RS3 in the sperm flagella.

Subunit / interactions. Component of the axonemal radial spoke complex. Interacts with RSPH3. Interacts with RSPH9.

Subcellular location. Cell projection. Cilium. Flagellum. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Expressed in spermatozoa.

Disease relevance. Spermatogenic failure 92 (SPGF92) [MIM:620848] An autosomal recessive, male infertility disorder characterized by asthenozoospermia and defects of the radial spokes and doublet microtubules of sperm flagellum observed by ultrastructural analysis. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53EV4-1	1	yes
Q53EV4-2	2

RefSeq proteins (3): NP_001128689, NP_008923, NP_964013 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050836	SDS22/Internalin_LRR	Family

Pfam: PF14580

UniProt features (23 total): repeat 8, sequence variant 4, region of interest 3, compositionally biased region 2, sequence conflict 2, chain 1, coiled-coil region 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53EV4-F1	88.03	0.80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, KORKOLA_CHORIOCARCINOMA_DN, KORKOLA_EMBRYONAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_CELL_PROJECTION_ORGANIZATION, HAN_SATB1_TARGETS_DN, GOBP_AXONEME_ASSEMBLY, MODULE_20, GOCC_MOTILE_CILIUM, GOCC_CILIUM, MODULE_13

GO Biological Process (2): flagellated sperm motility (GO:0030317), radial spoke assembly (GO:0062177)

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

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), sperm flagellum (GO:0036126), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
axoneme assembly	1
protein-containing complex assembly	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
9+2 motile cilium	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

1035 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC23	CFAP263	Q9H0I3	607
LRRC23	LRRC34	Q8IZ02	589
LRRC23	CFAP52	Q8N1V2	582
LRRC23	TSNAXIP1	Q2TAA8	570
LRRC23	RSPH14	Q9UHP6	540
LRRC23	CFAP161	Q6P656	539
LRRC23	CCDC146	Q8IYE0	519
LRRC23	LYPD2	Q6UXB3	471
LRRC23	PRR32	B1ATL7	465
LRRC23	LRRC20	Q8TCA0	462
LRRC23	WDR27	A2RRH5	461
LRRC23	RSPH10B	P0C881	460
LRRC23	SPATA18	Q8TC71	458
LRRC23	CCDC40	Q4G0X9	454
LRRC23	ZSWIM2	Q8NEG5	453

IntAct

8 interactions, top by confidence:

A	B	Type	Score
LRRC23	CEP55	psi-mi:“MI:0915”(physical association)	0.560
AK9	MYO9A	psi-mi:“MI:0914”(association)	0.350
IFITM3	PRAF2	psi-mi:“MI:0914”(association)	0.350
LRRC23	GATB	psi-mi:“MI:0914”(association)	0.350
OSTN	PEA15	psi-mi:“MI:0914”(association)	0.350
LRRC23	CEP55	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): LRRC23 (Affinity Capture-MS), CEP55 (Two-hybrid), LRRC23 (Affinity Capture-MS), LRRC40 (Affinity Capture-MS), GUF1 (Affinity Capture-MS), GATB (Affinity Capture-MS), MICU2 (Affinity Capture-MS), LRRC23 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), SUGT1 (Affinity Capture-MS), MTO1 (Affinity Capture-MS), JMJD4 (Affinity Capture-MS), LRRC23 (Affinity Capture-MS)

ESM2 similar proteins: A6QLV3, A7SFP1, A8XWW4, B0W6M9, B3LWU3, B3P3E8, B4IBI9, B4JTV9, B4LXW1, B4N9T4, B4PU77, B4QVR7, B5DX45, B6CZ61, B9F655, O35125, O88520, Q1L8Y7, Q22875, Q32KP2, Q4R3P6, Q4V8I7, Q53EV4, Q5F4C4, Q5FVI3, Q5GIG6, Q5M8G4, Q5RAV5, Q5RFE9, Q5ZLN0, Q6AYI5, Q6DHL5, Q6GPJ5, Q6INV3, Q6P1C6, Q6UXM1, Q6ZVD8, Q7SXW3, Q7Z4L9, Q80VQ1

Diamond homologs: B6CZ40, B6CZ45, B6CZ54, B6CZ61, O35125, O43822, P09661, P34390, P57784, Q16RY9, Q28CU0, Q32KP2, Q4R8Y8, Q4V8C9, Q53EV4, Q5EAD8, Q7PK92, Q8IYG6, Q8K375, Q96E66, Q9DAK8, A0A1L8G016, B3DH20, Q09JZ4, Q28FY0, Q6AYH9, Q8CDN9, P43333, Q6NRC9, Q6ZRR7, Q9BLB6, Q8C6G1, D4AC13, Q1X8D7, Q3UVD5, Q3V0M2, Q9HBX8, Q9U1H9, O62220, Q5ZMN0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	47
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3237373	NM_001135217.2(LRRC23):c.376C>T (p.Arg126Ter)	Pathogenic
3237374	NM_001135217.2(LRRC23):c.621+1G>A	Pathogenic

SpliceAI

1047 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6904974:GCA:G	donor_gain	1.0000
12:6905676:G:GT	donor_gain	1.0000
12:6905691:G:GT	donor_gain	1.0000
12:6905697:G:GT	donor_gain	1.0000
12:6905706:G:GT	donor_gain	1.0000
12:6905715:G:GT	donor_gain	1.0000
12:6905716:A:T	donor_gain	1.0000
12:6905742:G:GT	donor_gain	1.0000
12:6905742:G:T	donor_gain	1.0000
12:6905756:GGAA:G	donor_gain	1.0000
12:6905757:G:GT	donor_gain	1.0000
12:6905757:G:T	donor_gain	1.0000
12:6905757:GAA:G	donor_gain	1.0000
12:6905760:G:GG	donor_gain	1.0000
12:6905777:G:GT	donor_gain	1.0000
12:6906400:A:AG	acceptor_gain	1.0000
12:6906401:T:G	acceptor_gain	1.0000
12:6906405:CTAG:C	acceptor_loss	1.0000
12:6906407:A:AG	acceptor_gain	1.0000
12:6906407:A:G	acceptor_loss	1.0000
12:6906407:AG:A	acceptor_gain	1.0000
12:6906407:AGG:A	acceptor_gain	1.0000
12:6906408:G:A	acceptor_gain	1.0000
12:6906408:G:GG	acceptor_gain	1.0000
12:6906408:GGG:G	acceptor_gain	1.0000
12:6906408:GGGA:G	acceptor_gain	1.0000
12:6906408:GGGAC:G	acceptor_gain	1.0000
12:6906660:AAGG:A	donor_loss	1.0000
12:6906661:AGG:A	donor_loss	1.0000
12:6906662:GGT:G	donor_loss	1.0000

AlphaMissense

2250 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6909954:T:C	L229P	0.999
12:6910023:T:C	L252P	0.999
12:6906651:T:C	L160P	0.998
12:6906657:T:C	L162P	0.998
12:6910017:T:C	L250P	0.998
12:6910021:C:A	N251K	0.998
12:6910021:C:G	N251K	0.998
12:6910026:G:T	R253M	0.998
12:6906453:G:C	R94P	0.997
12:6906525:T:C	L118P	0.997
12:6906579:T:C	L136P	0.997
12:6906642:T:A	L157H	0.997
12:6907438:T:C	L205P	0.997
12:6907444:T:C	L207P	0.997
12:6909939:T:A	L224H	0.997
12:6909954:T:A	L229H	0.997
12:6909964:C:A	N232K	0.997
12:6909964:C:G	N232K	0.997
12:6910008:T:C	L247S	0.997
12:6910017:T:A	L250H	0.997
12:6912736:C:A	N255K	0.997
12:6912736:C:G	N255K	0.997
12:6912873:G:C	R301P	0.997
12:6906450:T:C	L93P	0.996
12:6906516:T:C	L115P	0.996
12:6906642:T:C	L157P	0.996
12:6907319:C:A	N165K	0.996
12:6907319:C:G	N165K	0.996
12:6907381:T:C	L186P	0.996
12:6909939:T:C	L224P	0.996

dbSNP variants (sampled 300 via entrez): RS1000161856 (12:6907725 T>G), RS1000287296 (12:6904937 T>C), RS1000412685 (12:6911344 A>G), RS1000589575 (12:6903196 G>T), RS1000618975 (12:6903365 A>G), RS1001654216 (12:6912109 C>G,T), RS1001804247 (12:6905144 G>C), RS1001984581 (12:6910623 C>T), RS1002015866 (12:6910966 C>G), RS1002539766 (12:6903844 C>A,G), RS1003211615 (12:6911768 G>A,T), RS1004027192 (12:6907150 A>C), RS1004633835 (12:6914331 T>C), RS1004954456 (12:6912503 A>C,G), RS1006335088 (12:6908311 A>G)

Disease associations

OMIM: gene MIM:620708 | disease phenotypes: MIM:620848

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 92	Moderate	Autosomal recessive

Mondo (1): spermatogenic failure 92 (MONDO:0970999)

Orphanet (0):

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0034011	Reduced progressive sperm motility
HP:0034811	Bent sperm flagella

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010002_206	Refractive error	3.000000e-62
GCST012495_4	Lung function (FEV1/FVC)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

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
bisphenol A	decreases methylation	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	increases expression	1
Decitabine	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Lead	affects expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Theophylline	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases methylation	1

Clinical trials (associated diseases)

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