LRRC46

Summary

LRRC46 (leucine rich repeat containing 46, HGNC:25047) is a protein-coding gene on chromosome 17q21.32, encoding Leucine-rich repeat-containing protein 46 (Q96FV0). Required for normal spermatogenesis and male fertility.

Predicted to be involved in sperm flagellum assembly. Predicted to act upstream of or within maintenance of cell number; single fertilization; and sperm flagellum assembly. Predicted to be active in sperm midpiece.

Source: NCBI Gene 90506 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_033413

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25047
Approved symbol	LRRC46
Name	leucine rich repeat containing 46
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	MGC16309
Ensembl gene	ENSG00000141294
Ensembl biotype	protein_coding
OMIM	620927
Entrez	90506

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 nonsense_mediated_decay, 2 protein_coding, 1 retained_intron

ENST00000269025, ENST00000579742, ENST00000579971, ENST00000584580, ENST00000584809, ENST00000955155

RefSeq mRNA: 1 — MANE Select: NM_033413 NM_033413

CCDS: CCDS11518

Canonical transcript exons

ENST00000269025 — 8 exons

Exon	Start	End
ENSE00001137672	47836750	47837719
ENSE00001137678	47832100	47832205
ENSE00001194356	47831670	47831999
ENSE00003490557	47834425	47834533
ENSE00003543669	47835353	47835399
ENSE00003597344	47836333	47836475
ENSE00003692240	47835666	47835775
ENSE00003692335	47836033	47836102

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6674 / max 546.7150, expressed in 1159 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161380	2.7699	1110
161382	0.5765	79
161381	0.1702	41
161379	0.1507	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.23	gold quality
bronchial epithelial cell	CL:0002328	99.08	gold quality
bronchus	UBERON:0002185	98.65	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.03	gold quality
left testis	UBERON:0004533	94.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.71	gold quality
right testis	UBERON:0004534	94.20	gold quality
testis	UBERON:0000473	92.03	gold quality
nasal cavity epithelium	UBERON:0005384	90.15	gold quality
oviduct epithelium	UBERON:0004804	89.43	gold quality
fallopian tube	UBERON:0003889	88.53	gold quality
trachea	UBERON:0003126	87.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.44	gold quality
epithelium of nasopharynx	UBERON:0001951	82.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.83	gold quality
nasal cavity mucosa	UBERON:0001826	81.51	gold quality
adult organism	UBERON:0007023	81.28	gold quality
caput epididymis	UBERON:0004358	79.32	gold quality
sperm	CL:0000019	79.12	gold quality
right lung	UBERON:0002167	78.96	gold quality
pancreatic ductal cell	CL:0002079	78.83	silver quality
epithelial cell of pancreas	CL:0000083	76.19	gold quality
superior vestibular nucleus	UBERON:0007227	76.14	gold quality
vena cava	UBERON:0004087	75.19	silver quality
cerebellar vermis	UBERON:0004720	73.73	gold quality
left uterine tube	UBERON:0001303	73.52	gold quality
medulla oblongata	UBERON:0001896	72.40	gold quality
pericardium	UBERON:0002407	71.13	silver quality
cerebellar hemisphere	UBERON:0002245	70.83	gold quality
cerebellar cortex	UBERON:0002129	70.81	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	62.43
E-HCAD-1	yes	26.08
E-MTAB-10287	yes	25.45
E-ANND-3	yes	10.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting LRRC46, 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-4481	100.00	66.42	1669
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-1238-5P	94.82	67.52	493
HSA-MIR-4758-5P	94.82	67.06	499
HSA-MIR-6812-3P	90.58	63.80	60

Literature-anchored findings (GeneRIF, showing 1)

• Identification of LRRC46 as a novel candidate gene for high myopia. (PMID:38874710)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc46	ENSMUSG00000020878
rattus_norvegicus	Lrrc46	ENSRNOG00000009902
drosophila_melanogaster	TbCMF46	FBGN0032163
drosophila_melanogaster	Ppr-Y	FBGN0046697
caenorhabditis_elegans		WBGENE00020266

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), DNAAF1 (ENSG00000154099), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), DRC3 (ENSG00000171962), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 46 — Q96FV0 (reviewed: Q96FV0)

All UniProt accessions (3): Q96FV0, J3KSP7, J3QQW4

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal spermatogenesis and male fertility. Plays an important role in sperm flagellum biogenesis.

Subunit / interactions. Interacts with CCDC181; interaction is essential for its proper localization to sperm flagella.

Subcellular location. Cell projection. Cilium. Flagellum.

RefSeq proteins (1): NP_219481* (*=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
IPR050576	Cilia_flagella_integrity	Family

Pfam: PF13855

UniProt features (10 total): repeat 4, modified residue 2, chain 1, domain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FV0-F1	64.85	0.06

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): 175, 182

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, CYTAGCAAY_UNKNOWN, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_FERTILIZATION, GOBP_AXONEME_ASSEMBLY

GO Biological Process (8): spermatogenesis (GO:0007283), sperm axoneme assembly (GO:0007288), single fertilization (GO:0007338), maintenance of cell number (GO:0098727), sperm flagellum assembly (GO:0120316), sperm mitochondrial sheath assembly (GO:0120317), spermatid development (GO:0007286), cell differentiation (GO:0030154)

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

GO Cellular Component (5): sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	3
sperm flagellum assembly	2
cellular anatomical structure	2
male gamete generation	1
axoneme assembly	1
fertilization	1
developmental process	1
spermatid development	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component assembly	1
germ cell development	1
spermatid differentiation	1
cellular developmental process	1
binding	1
9+2 motile cilium	1
sperm flagellum	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

1233 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC46	CFAP161	Q6P656	644
LRRC46	CFAP57	Q96MR6	519
LRRC46	DRC7	Q8IY82	473
LRRC46	BET1L	Q9NYM9	465
LRRC46	SHCBP1	Q8NEM2	457
LRRC46	E5RHQ9	E5RHQ9	445
LRRC46	ZNF284	Q2VY69	431
LRRC46	CFAP221	Q4G0U5	430
LRRC46	TSNAXIP1	Q2TAA8	427
LRRC46	WDR49	Q8IV35	422
LRRC46	ASCC2	Q9H1I8	421
LRRC46	ZBBX	A8MT70	418
LRRC46	RSPH14	Q9UHP6	416
LRRC46	SAXO2	Q658L1	413
LRRC46	ZSWIM2	Q8NEG5	411
LRRC46	RUNDC1	Q96C34	411

IntAct

15 interactions, top by confidence:

A	B	Type	Score
LRRC46	TFPT	psi-mi:“MI:0914”(association)	0.640
LRRC46	TBP	psi-mi:“MI:0914”(association)	0.640
DNAJC28	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
TSSC4	SNRNP200	psi-mi:“MI:0914”(association)	0.530
SLC35A4	LRRC46	psi-mi:“MI:0915”(physical association)	0.400
LRRC46		psi-mi:“MI:0915”(physical association)	0.400
PITX2	AHCYL1	psi-mi:“MI:0914”(association)	0.350
CFAP184	UTRN	psi-mi:“MI:0914”(association)	0.350
LRRC46	GTPBP6	psi-mi:“MI:0914”(association)	0.350
PIGH	PRAF2	psi-mi:“MI:0914”(association)	0.350
UCHL5	KIF2A	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): LRRC46 (Affinity Capture-MS), PACS2 (Affinity Capture-MS), HADHB (Affinity Capture-MS), RRP7A (Affinity Capture-MS), POLE (Affinity Capture-MS), OSBP (Affinity Capture-MS), TYK2 (Affinity Capture-MS), HJURP (Affinity Capture-MS), FZR1 (Affinity Capture-MS), POLE2 (Affinity Capture-MS), WDR37 (Affinity Capture-MS), UQCC1 (Affinity Capture-MS), SIX4 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS)

ESM2 similar proteins: A0JM56, A2RRS8, A6H759, A6NJI9, B1ANS9, D3ZXS4, D4A039, F1MCA7, P62046, P70587, Q0V9Y8, Q3U3V8, Q3UMG5, Q3V0L5, Q4KLV2, Q4R747, Q5F479, Q5JTW2, Q5PPX0, Q5SUS0, Q5VUJ6, Q5XGI3, Q5XX13, Q6AXZ2, Q6GQN5, Q6INS1, Q6IRN0, Q6IRU7, Q6P2D8, Q6P5J6, Q80TE7, Q8BGI7, Q8C008, Q8C0Q4, Q8C0W1, Q8C2S5, Q8C6G1, Q8CDN9, Q8IZ02, Q96FV0

Diamond homologs: Q4R747, Q6AXZ2, Q96FV0, Q9DAP0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1229 predictions. Top by Δscore:

Variant	Effect	Δscore
17:47832203:GAT:G	donor_gain	1.0000
17:47832204:ATGTG:A	donor_loss	1.0000
17:47832205:TG:T	donor_loss	1.0000
17:47832206:G:GG	donor_gain	1.0000
17:47832207:T:G	donor_loss	1.0000
17:47834421:CCA:C	acceptor_loss	1.0000
17:47834422:CA:C	acceptor_loss	1.0000
17:47834423:A:C	acceptor_loss	1.0000
17:47834488:G:GT	donor_gain	1.0000
17:47834530:AGGGG:A	donor_loss	1.0000
17:47834531:G:GT	donor_gain	1.0000
17:47834531:GGG:G	donor_gain	1.0000
17:47834532:GG:G	donor_gain	1.0000
17:47834532:GGG:G	donor_gain	1.0000
17:47834532:GGGTA:G	donor_loss	1.0000
17:47834533:G:T	donor_gain	1.0000
17:47834533:GG:G	donor_gain	1.0000
17:47834533:GGTAA:G	donor_loss	1.0000
17:47834534:GTA:G	donor_loss	1.0000
17:47834535:T:A	donor_loss	1.0000
17:47835771:GCTGG:G	donor_gain	1.0000
17:47835772:C:G	donor_gain	1.0000
17:47836021:T:A	acceptor_gain	1.0000
17:47836024:T:A	acceptor_gain	1.0000
17:47836031:A:AG	acceptor_gain	1.0000
17:47836031:AGAT:A	acceptor_gain	1.0000
17:47836032:G:GA	acceptor_gain	1.0000
17:47836032:GA:G	acceptor_gain	1.0000
17:47836032:GAT:G	acceptor_gain	1.0000
17:47836032:GATG:G	acceptor_gain	1.0000

AlphaMissense

2082 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:47834454:T:A	V49D	0.993
17:47835692:T:C	I100T	0.993
17:47835667:T:C	F92L	0.992
17:47835669:C:A	F92L	0.992
17:47835669:C:G	F92L	0.992
17:47835743:T:C	L117P	0.992
17:47835360:T:C	I78T	0.991
17:47835753:C:A	N120K	0.991
17:47835753:C:G	N120K	0.991
17:47836060:T:C	L137P	0.989
17:47835686:A:T	N98I	0.987
17:47835687:C:A	N98K	0.987
17:47835687:C:G	N98K	0.987
17:47835396:T:C	L90S	0.986
17:47835752:A:T	N120I	0.986
17:47834520:T:A	L71H	0.984
17:47834526:T:C	L73P	0.984
17:47835671:T:A	L93Q	0.984
17:47835671:T:C	L93P	0.984
17:47835743:T:A	L117H	0.984
17:47835752:A:C	N120T	0.984
17:47836060:T:A	L137H	0.984
17:47835737:T:C	L115P	0.983
17:47834475:T:C	I56T	0.982
17:47835692:T:G	I100S	0.982
17:47835728:T:A	L112H	0.982
17:47836066:T:C	L139P	0.982
17:47835354:A:T	N76I	0.981
17:47835751:A:C	N120H	0.981
17:47835751:A:G	N120D	0.981

dbSNP variants (sampled 300 via entrez): RS1000162850 (17:47832104 G>A), RS1000923603 (17:47836032 G>A,C), RS1003140256 (17:47832569 G>A), RS1003146794 (17:47837474 T>C), RS1003257863 (17:47831953 T>C), RS1003336918 (17:47833703 C>T), RS1003412882 (17:47832045 G>A,C), RS1003885174 (17:47834014 G>T), RS1004285207 (17:47833209 A>G), RS1004720991 (17:47832972 A>C), RS1004977530 (17:47829782 A>G,T), RS1005027605 (17:47834800 A>G), RS1005319751 (17:47831343 G>A), RS1005449950 (17:47838156 T>C), RS1005458791 (17:47833592 G>A)

Disease associations

OMIM: gene MIM:620927 | 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
GCST005951_17	Body mass index	3.000000e-09
GCST008916_117	Asthma	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	increases abundance, increases expression	2
aminomethylphosphonic acid (AMPA)	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Glyphosate	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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