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LRGUK

gene
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Also known as FLJ32786CFAP246

Summary

LRGUK (leucine rich repeats and guanylate kinase domain containing, HGNC:21964) is a protein-coding gene on chromosome 7q33, encoding Leucine-rich repeat and guanylate kinase domain-containing protein (Q96M69). Involved in multiple aspects of sperm assembly including acrosome attachment, shaping of the sperm head and in the early aspects of axoneme development.

Predicted to enable guanylate kinase activity. Predicted to be involved in axoneme assembly and spermatogenesis. Predicted to be located in acrosomal vesicle and manchette. Predicted to be active in cytosol.

Source: NCBI Gene 136332 — RefSeq curated summary.

At a glance

  • GWAS associations: 3
  • Clinical variants (ClinVar): 133 total
  • MANE Select transcript: NM_144648

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:21964
Approved symbolLRGUK
Nameleucine rich repeats and guanylate kinase domain containing
Location7q33
Locus typegene with protein product
StatusApproved
AliasesFLJ32786, CFAP246
Ensembl geneENSG00000155530
Ensembl biotypeprotein_coding
OMIM616478
Entrez136332

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000285928, ENST00000473068, ENST00000645682, ENST00000695542, ENST00000695543

RefSeq mRNA: 4 — MANE Select: NM_144648 NM_001365700, NM_001365701, NM_001401519, NM_144648

CCDS: CCDS5830, CCDS94203, CCDS94204

Canonical transcript exons

ENST00000285928 — 20 exons

ExonStartEnd
ENSE00000833228134163397134163540
ENSE00001021343134158035134158159
ENSE00001021349134174556134174636
ENSE00001021350134178503134178609
ENSE00001021351134176977134177063
ENSE00001021352134183734134183853
ENSE00001021353134191655134191751
ENSE00001021360134258257134258405
ENSE00001086571134143062134143162
ENSE00001086572134248951134249076
ENSE00001086579134247556134247644
ENSE00001086580134148238134148319
ENSE00001086581134221779134221918
ENSE00001175610134201481134201576
ENSE00001175613134199220134199421
ENSE00001175617134196992134197105
ENSE00001292305134263845134264595
ENSE00003499047134137023134137130
ENSE00003613525134139436134139517
ENSE00003964227134127340134127664

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 83.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3930 / max 34.2825, expressed in 160 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
812520.3930160

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
bronchial epithelial cellCL:000232883.36gold quality
bronchusUBERON:000218582.04gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047378.78gold quality
spermCL:000001976.45gold quality
olfactory segment of nasal mucosaUBERON:000538675.42gold quality
right uterine tubeUBERON:000130273.32gold quality
oviduct epitheliumUBERON:000480472.75gold quality
buccal mucosa cellCL:000233672.51gold quality
pancreatic ductal cellCL:000207971.68silver quality
tibialis anteriorUBERON:000138569.13silver quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099167.69gold quality
left testisUBERON:000453367.57gold quality
testisUBERON:000047367.32gold quality
ventricular zoneUBERON:000305366.71gold quality
mucosa of paranasal sinusUBERON:000503066.26gold quality
right testisUBERON:000453466.11gold quality
fallopian tubeUBERON:000388965.45gold quality
nasal cavity epitheliumUBERON:000538465.32silver quality
ileal mucosaUBERON:000033163.44silver quality
epithelium of nasopharynxUBERON:000195162.66gold quality
nasal cavity mucosaUBERON:000182662.60gold quality
bone marrow cellCL:000209261.60gold quality
granulocyteCL:000009460.20gold quality
ganglionic eminenceUBERON:000402359.68gold quality
deltoidUBERON:000147659.42silver quality
cortical plateUBERON:000534359.23gold quality
body of pancreasUBERON:000115057.71gold quality
caput epididymisUBERON:000435856.95gold quality
calcaneal tendonUBERON:000370156.82gold quality
metanephros cortexUBERON:001053356.31gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes7.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting LRGUK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-548AE-3P99.9372.664867
HSA-MIR-548AH-3P99.9372.544872
HSA-MIR-548AM-3P99.9372.544872
HSA-MIR-548AQ-3P99.9372.664867
HSA-MIR-124-3P99.8973.743043
HSA-MIR-506-3P99.8973.553057
HSA-MIR-6875-3P99.8270.262983
HSA-MIR-371499.7170.742671
HSA-MIR-94099.3766.142064
HSA-MIR-450699.3467.47526
HSA-MIR-6808-5P99.3166.232150
HSA-MIR-6893-5P99.3166.252119
HSA-MIR-3064-5P99.2666.131497
HSA-MIR-3085-3P99.2666.161490
HSA-MIR-6504-5P99.2665.951487
HSA-MIR-3940-5P99.1465.26493
HSA-MIR-450799.1465.27515
HSA-MIR-6809-5P99.1368.451223
HSA-MIR-92299.0267.231838
HSA-MIR-1207-3P98.9966.221532
HSA-MIR-4716-5P98.8268.571168
HSA-MIR-473697.9665.891287
HSA-MIR-125896.0867.74700

Literature-anchored findings (GeneRIF, showing 2)

  • Study demonstrates that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. (PMID:25781171)
  • The structure revealed that hGMPK consists of three distinct regions designated as the LID, GMP-binding (GMP-BD), and CORE domains and is in an open configuration that is nucleotide binding-competent. Nonsynonymous single-nucleotide variants of the hGMPK CORE domain distant from the nucleotide-binding site of this domain modulate enzymatic activity without significantly affecting hGMPK’s structure. (PMID:31201273)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriolrgukENSDARG00000069698
mus_musculusLrgukENSMUSG00000056215
rattus_norvegicusLrgukENSRNOG00000008775
drosophila_melanogasterTbCMF46FBGN0032163
drosophila_melanogasterPpr-YFBGN0046697

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), DNAAF1 (ENSG00000154099), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), DRC3 (ENSG00000171962), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Leucine-rich repeat and guanylate kinase domain-containing protein — Q96M69 (reviewed: Q96M69)

All UniProt accessions (4): Q96M69, A0A2R8YEJ5, A0A8Q3SI13, A0A8Q3SIT3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in multiple aspects of sperm assembly including acrosome attachment, shaping of the sperm head and in the early aspects of axoneme development. Not essential for primary cilium biogenesis.

Subunit / interactions. Interacts (via guanylate kinase-like domain) with RIMBP3 (via coiled-coil region). Interacts (via guanylate kinase-like domain) with HOOK2. Interacts (via LRRCT domain) with KLC3. Interacts with HOOK1 and HOOK3.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Cytoplasm. Cytoskeleton. Cilium basal body.

RefSeq proteins (4): NP_001352629, NP_001352630, NP_001388448, NP_653249* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001611Leu-rich_rptRepeat
IPR008144Guanylate_kin-like_domDomain
IPR008145GK/Ca_channel_bsuDomain
IPR025875Leu-rich_rpt_4Repeat
IPR027417P-loop_NTPaseHomologous_superfamily
IPR032675LRR_dom_sfHomologous_superfamily

Pfam: PF00625, PF12799, PF14580

UniProt features (20 total): repeat 9, domain 2, region of interest 2, compositionally biased region 2, sequence variant 2, chain 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96M69-F170.420.50

Functional residue map

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

Ligand- & substrate-binding residues (1): 421–428

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOCC_SECRETORY_GRANULE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BRN2_01, GOBP_CILIUM_ORGANIZATION, GATA6_01, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GATA1_03, NKX25_01, GOBP_GDP_METABOLIC_PROCESS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION

GO Biological Process (5): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), axoneme assembly (GO:0035082), GMP metabolic process (GO:0046037), GDP metabolic process (GO:0046710)

GO Molecular Function (6): GMP kinase activity (GO:0004385), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): acrosomal vesicle (GO:0001669), manchette (GO:0002177), cytosol (GO:0005829), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
purine ribonucleotide metabolic process2
cytoplasm2
developmental process involved in reproduction1
male gamete generation1
cellular developmental process1
microtubule bundle formation1
cellular component assembly1
cilium assembly1
purine ribonucleoside monophosphate metabolic process1
purine ribonucleoside diphosphate metabolic process1
GMP metabolic process1
GDP metabolic process1
nucleoside monophosphate kinase activity1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
nucleoside phosphate binding1
heterocyclic compound binding1
binding1
transferase activity, transferring phosphorus-containing groups1
catalytic activity1
secretory granule1
microtubule cytoskeleton1
intracellular anatomical structure1
intracellular membraneless organelle1
intracellular vesicle1

Protein interactions and networks

STRING

6169 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
LRGUKSPEF2Q9C093589
LRGUKSVOPLQ8N434572
LRGUKSSMEM1Q8WWF3564
LRGUKNAT9Q9BTE0561
LRGUKWDR62O43379528
LRGUKHOOK1Q9UJC3526
LRGUKC18orf63Q68DL7507
LRGUKCFAP99D6REC4495
LRGUKCOQ9O75208493
LRGUKRAD51AP1Q96B01490
LRGUKTSSK4Q6SA08490
LRGUKNEU2Q9Y3R4488
LRGUKMORN3Q6PF18488
LRGUKCCDC40Q4G0X9482
LRGUKSPACA1Q9HBV2480

IntAct

6 interactions, top by confidence:

ABTypeScore
HOOK2LRGUKpsi-mi:“MI:0915”(physical association)0.560
LRGUKpsi-mi:“MI:0915”(physical association)0.400
PB2psi-mi:“MI:0914”(association)0.350
LRGUKHOOK2psi-mi:“MI:0915”(physical association)0.000

BioGRID (2): LRGUK (Two-hybrid), LRGUK (Affinity Capture-MS)

ESM2 similar proteins: A0A494C086, A0A494C0Z2, A0A494C191, A0JPH4, A6NHP3, A6NIY4, A6NJR5, A6NLX3, A6NNV3, A6QLI5, B0BNE4, O08918, O60543, O70302, O75916, P0CI01, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P24864, P39949, P49805, Q12967, Q495Y7, Q495Y8, Q4VXA5, Q4ZIN3, Q5IBH6, Q5IBH7, Q5MJ70, Q5SYB0, Q5XIQ2, Q5ZJR9, Q61457, Q6AYG1

Diamond homologs: B6CZ40, B6CZ45, B6CZ54, B6CZ61, O35125, O43822, P34390, P39687, P51122, P97822, Q28CU0, Q28XE2, Q32KP2, Q3SZC6, Q4WV66, Q53EV4, Q5BGW9, Q5EAD8, Q5F4A3, Q5XIE0, Q6A1I3, Q6PAF6, Q7ZUP0, Q7ZY40, Q8C6G1, Q8HY67, Q8K375, Q92688, Q96E66, Q96M69, Q9BTT0, Q9DAK8, Q9NJE9, Q9V895, Q64520, Q7U570, Q9D5S7, Q16774, Q9KNM4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance110
Likely benign10
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4222 predictions. Top by Δscore:

VariantEffectΔscore
7:134127662:G:GTdonor_gain1.0000
7:134137010:G:Aacceptor_gain1.0000
7:134137131:G:GGdonor_gain1.0000
7:134139431:CTCAG:Cacceptor_loss1.0000
7:134139433:CAGG:Cacceptor_loss1.0000
7:134139434:A:AGacceptor_gain1.0000
7:134139434:AG:Aacceptor_gain1.0000
7:134139435:G:Aacceptor_loss1.0000
7:134139435:G:GGacceptor_gain1.0000
7:134139435:GG:Gacceptor_gain1.0000
7:134139435:GGGTT:Gacceptor_gain1.0000
7:134139513:TGAAG:Tdonor_loss1.0000
7:134139514:GAAGG:Gdonor_loss1.0000
7:134139517:GGT:Gdonor_loss1.0000
7:134139518:GTAT:Gdonor_loss1.0000
7:134139519:T:Gdonor_loss1.0000
7:134163392:TTTA:Tacceptor_loss1.0000
7:134163393:TTA:Tacceptor_loss1.0000
7:134163394:TA:Tacceptor_loss1.0000
7:134163395:A:AGacceptor_gain1.0000
7:134163396:G:GAacceptor_gain1.0000
7:134163396:GA:Gacceptor_gain1.0000
7:134163396:GAGC:Gacceptor_gain1.0000
7:134163396:GAGCA:Gacceptor_gain1.0000
7:134163514:G:GTdonor_gain1.0000
7:134163532:GATAA:Gdonor_gain1.0000
7:134163536:ATAAG:Adonor_loss1.0000
7:134163537:TAAGG:Tdonor_loss1.0000
7:134163538:AAGGT:Adonor_loss1.0000
7:134163539:AGG:Adonor_loss1.0000

AlphaMissense

5437 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
7:134143101:T:CL176P0.995
7:134183781:G:AG421D0.995
7:134197035:G:AG492E0.995
7:134199220:G:CG516R0.995
7:134163461:T:CL287P0.994
7:134163527:T:CL309P0.994
7:134183780:G:CG421R0.994
7:134191713:T:CF465L0.994
7:134191715:T:AF465L0.994
7:134191715:T:GF465L0.994
7:134196999:T:CF480S0.994
7:134199266:T:CL531P0.994
7:134148308:T:CL220P0.993
7:134158089:T:CL242P0.993
7:134177032:T:CL359S0.993
7:134196992:G:TG478W0.993
7:134143158:T:CL195P0.992
7:134174611:T:CL332P0.992
7:134174617:T:CL334P0.992
7:134197082:A:CS508R0.992
7:134197084:C:AS508R0.992
7:134197084:C:GS508R0.992
7:134143092:T:AL173H0.991
7:134143092:T:CL173P0.991
7:134174605:G:CR330P0.991
7:134177023:T:CL356S0.991
7:134196993:G:TG478V0.991
7:134143158:T:AL195H0.990
7:134178509:G:CA372P0.990
7:134191672:G:CR451T0.990

dbSNP variants (sampled 300 via entrez): RS1000000136 (7:134259955 G>A), RS1000031189 (7:134142672 A>G), RS1000059334 (7:134130547 G>A,C), RS1000088897 (7:134215210 C>T), RS1000103373 (7:134184371 A>C), RS1000129307 (7:134159021 G>A,T), RS1000155850 (7:134274648 T>C), RS1000160584 (7:134209311 A>G), RS1000182974 (7:134258086 A>G), RS1000204836 (7:134266097 A>G), RS1000217419 (7:134276264 A>T), RS1000238108 (7:134255425 T>A,C), RS1000244311 (7:134159260 C>T), RS1000248216 (7:134267935 T>A), RS1000274106 (7:134202392 G>A)

Disease associations

OMIM: gene MIM:616478 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

StudyTraitp-value
GCST005024_74Pursuit maintenance gain4.000000e-06
GCST007326_27Number of sexual partners6.000000e-11
GCST007327_80Smoking status (ever vs never smokers)5.000000e-08

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0008433pursuit maintenance gain measurement
EFO:0004318smoking behavior

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.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyrenedecreases methylation, increases expression2
bisphenol Aaffects methylation1
butyraldehydedecreases expression1
benzo(e)pyrenedecreases methylation1
abrineincreases expression1
licochalcone Bdecreases expression1
jinfukangaffects cotreatment, decreases expression1
Cisplatinaffects cotreatment, decreases expression1
Malathiondecreases expression1
Methapyrilenedecreases methylation1
Silicon Dioxidedecreases expression1
Tobacco Smoke Pollutiondecreases expression1
Okadaic Acidincreases expression1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot