LRRC37A3

Summary

LRRC37A3 (leucine rich repeat containing 37 member A3, HGNC:32427) is a protein-coding gene on chromosome 17q24.1, encoding Leucine-rich repeat-containing protein 37A3 (O60309). It is a selective cancer dependency (DepMap: 36.8% of cell lines).

Predicted to be located in membrane.

Source: NCBI Gene 374819 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 223 total
• Cancer dependency (DepMap): dependent in 36.8% of screened cell lines
• MANE Select transcript: NM_199340

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32427
Approved symbol	LRRC37A3
Name	leucine rich repeat containing 37 member A3
Location	17q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34306, KIAA0563
Ensembl gene	ENSG00000176809
Ensembl biotype	protein_coding
OMIM	616557
Entrez	374819

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000319651, ENST00000334962, ENST00000339474, ENST00000400877, ENST00000577487, ENST00000579305, ENST00000580439, ENST00000580464, ENST00000581368, ENST00000583510, ENST00000584306, ENST00000584788

RefSeq mRNA: 2 — MANE Select: NM_199340 NM_001303255, NM_199340

CCDS: CCDS32708, CCDS77091

Canonical transcript exons

ENST00000584306 — 15 exons

Exon	Start	End
ENSE00001222140	64858779	64858883
ENSE00001540364	64898362	64898459
ENSE00002369473	64855840	64855889
ENSE00002385149	64859442	64860973
ENSE00002689169	64918750	64918870
ENSE00002722312	64894649	64897654
ENSE00003511475	64868462	64868536
ENSE00003526242	64869095	64869166
ENSE00003529482	64889681	64889752
ENSE00003547821	64892529	64892600
ENSE00003564889	64886086	64886166
ENSE00003642322	64886815	64886886
ENSE00003669518	64862900	64863018
ENSE00003916060	64854130	64854644
ENSE00003917483	64919431	64919478

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 92.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6138 / max 98.6419, expressed in 1607 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167605	7.6138	1607

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	92.15	gold quality
bone marrow cell	CL:0002092	91.47	gold quality
right testis	UBERON:0004534	90.65	gold quality
left testis	UBERON:0004533	90.54	gold quality
adenohypophysis	UBERON:0002196	90.26	gold quality
pituitary gland	UBERON:0000007	89.71	gold quality
calcaneal tendon	UBERON:0003701	89.61	gold quality
testis	UBERON:0000473	88.84	gold quality
left lobe of thyroid gland	UBERON:0001120	88.58	gold quality
right lobe of thyroid gland	UBERON:0001119	88.38	gold quality
cerebellar hemisphere	UBERON:0002245	88.34	gold quality
thyroid gland	UBERON:0002046	88.33	gold quality
cerebellar cortex	UBERON:0002129	88.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.28	gold quality
colonic epithelium	UBERON:0000397	87.66	gold quality
cerebellum	UBERON:0002037	87.28	gold quality
buccal mucosa cell	CL:0002336	86.92	silver quality
sural nerve	UBERON:0015488	86.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.08	gold quality
hypothalamus	UBERON:0001898	86.02	gold quality
tendon	UBERON:0000043	85.70	gold quality
right frontal lobe	UBERON:0002810	85.62	gold quality
metanephros cortex	UBERON:0010533	84.94	gold quality
cortical plate	UBERON:0005343	84.51	gold quality
nucleus accumbens	UBERON:0001882	84.35	gold quality
sperm	CL:0000019	84.30	gold quality
ventricular zone	UBERON:0003053	84.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.28	gold quality
anterior cingulate cortex	UBERON:0009835	84.26	gold quality
caudate nucleus	UBERON:0001873	83.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting LRRC37A3, 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-6721-5P	99.93	68.92	2981
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-151A-3P	95.52	65.29	516

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 36.8% of screened cell lines.

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc37	ENSMUSG00000034239
mus_musculus	Lrrc37a	ENSMUSG00000078632
rattus_norvegicus	Lrrc37a	ENSRNOG00000042025
rattus_norvegicus	Prp2l1	ENSRNOG00000042833

Paralogs (3): LRRC37A (ENSG00000176681), LRRC37B (ENSG00000185158), LRRC37A2 (ENSG00000238083)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 37A3 — O60309 (reviewed: O60309)

All UniProt accessions (8): B4DSF2, O60309, F8W7X0, J3KT91, J3KT96, J3QKQ2, J3QL27, J3QTJ5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the LRRC37A family.

RefSeq proteins (2): NP_001290184, NP_955372* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR015753	LRRC37	Family
IPR029423	LRRC37AB_C	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR032754	LRRC37_N	Domain

Pfam: PF13855, PF14914, PF15779

UniProt features (45 total): repeat 12, compositionally biased region 11, region of interest 8, sequence conflict 5, topological domain 2, glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60309-F1	42.62	0.11

Functional residue map

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

Glycosylation sites (2): 296, 1079

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GREGORY_SYNTHETIC_LETHAL_WITH_IMATINIB, DUAN_PRDM5_TARGETS, CBX5_TARGET_GENES, CHAF1B_TARGET_GENES, H1_6_TARGET_GENES, HMGA1_TARGET_GENES, TFEB_TARGET_GENES, UBN1_TARGET_GENES, WDHD1_TARGET_GENES, ZNF30_TARGET_GENES, ZNF354B_TARGET_GENES, ZNF407_TARGET_GENES, ZNF410_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC37A3	KANSL1	Q7Z3B3	724
LRRC37A3	ARL17B	I3L3L1	720
LRRC37A3	ARL17A	Q8IVW1	712
LRRC37A3	SPDYE5	A6NIY4	608
LRRC37A3	CRHR1	P34998	507
LRRC37A3	ARHGAP27	Q6ZUM4	506
LRRC37A3	TCP11	Q8WWU5	495
LRRC37A3	MAPT	P10636	475
LRRC37A3	NPIPB11	E5RHQ5	447
LRRC37A3	NPIPA5	E9PKD4	447
LRRC37A3	NPIPA3	F8WFD2	446
LRRC37A3	FLACC1	Q96Q35	434
LRRC37A3	PLEKHM1	Q9Y4G2	431
LRRC37A3	SPPL2C	Q8IUH8	430
LRRC37A3	PRPF8	Q6P2Q9	407

IntAct

0 interactions, top by confidence:

BioGRID (5): LRRC37A3 (Affinity Capture-RNA), LRRC37A3 (Proximity Label-MS), LRRC37A3 (Negative Genetic), LRRC37A3 (Negative Genetic), LRRC37A3 (Negative Genetic)

ESM2 similar proteins: A0A1B0GUW6, A1EGX6, A6NM11, A6NMS7, A6QLF8, D3YU32, I3L273, J3KML8, O35930, O60309, Q08DY0, Q14242, Q2TBI7, Q32KG4, Q32L62, Q3MIW9, Q3TNW5, Q3V0E1, Q4R729, Q5VWK0, Q5VYM1, Q62170, Q659K0, Q68DN1, Q6AZ54, Q6MG22, Q6UXB8, Q6ZRG5, Q8BUE7, Q8K4E0, Q8N307, Q8N3K9, Q8TCU4, Q8WNU4, Q8WXI7, Q95JY5, Q96F05, Q96JA4, Q96M34, Q96M43

Diamond homologs: A6NM11, A6NMS7, O60309, Q49AS3, Q96QE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	184
Likely benign	26
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1895 predictions. Top by Δscore:

Variant	Effect	Δscore
17:64855835:TTTAC:T	donor_loss	1.0000
17:64855837:TACCT:T	donor_loss	1.0000
17:64855838:ACCTT:A	donor_loss	1.0000
17:64855885:CAGAT:C	acceptor_gain	1.0000
17:64855887:GAT:G	acceptor_gain	1.0000
17:64855887:GATC:G	acceptor_loss	1.0000
17:64855888:ATC:A	acceptor_loss	1.0000
17:64855889:TCT:T	acceptor_loss	1.0000
17:64855890:C:CC	acceptor_gain	1.0000
17:64855890:CT:C	acceptor_loss	1.0000
17:64855895:T:C	acceptor_gain	1.0000
17:64855895:T:TC	acceptor_gain	1.0000
17:64858884:C:CC	acceptor_gain	1.0000
17:64862864:A:AC	donor_gain	1.0000
17:64862865:A:C	donor_gain	1.0000
17:64862898:A:AC	donor_gain	1.0000
17:64862899:C:CC	donor_gain	1.0000
17:64862899:CGA:C	donor_gain	1.0000
17:64868460:A:AC	donor_gain	1.0000
17:64868461:C:CC	donor_gain	1.0000
17:64868461:CAG:C	donor_gain	1.0000
17:64886085:CAA:C	donor_gain	1.0000
17:64886813:A:AC	donor_gain	1.0000
17:64886814:C:CC	donor_gain	1.0000
17:64889675:A:AC	donor_gain	1.0000
17:64889676:C:CC	donor_gain	1.0000
17:64889679:A:AC	donor_gain	1.0000
17:64889680:C:CC	donor_gain	1.0000
17:64855838:A:AC	donor_gain	0.9900
17:64855839:C:CC	donor_gain	0.9900

AlphaMissense

10637 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:64886151:A:C	N947K	0.984
17:64886151:A:T	N947K	0.984
17:64886871:A:C	N923K	0.982
17:64886871:A:T	N923K	0.982
17:64886872:T:A	N923I	0.981
17:64886866:A:G	I925T	0.980
17:64889737:A:C	N899K	0.979
17:64889737:A:T	N899K	0.979
17:64892529:A:G	L894P	0.978
17:64892557:A:G	W885R	0.977
17:64892557:A:T	W885R	0.977
17:64869095:A:G	L993P	0.976
17:64889723:A:G	L904S	0.976
17:64892555:C:A	W885C	0.975
17:64892555:C:G	W885C	0.975
17:64892595:A:G	F872S	0.975
17:64886841:A:C	F933L	0.974
17:64886841:A:T	F933L	0.974
17:64886843:A:G	F933L	0.974
17:64886866:A:T	I925K	0.973
17:64892585:G:C	N875K	0.973
17:64892585:G:T	N875K	0.973
17:64889732:A:G	L901S	0.972
17:64889738:T:A	N899I	0.971
17:64886161:A:G	L944P	0.968
17:64889747:A:G	L896P	0.968
17:64886152:T:A	N947I	0.967
17:64868462:A:G	L1018P	0.966
17:64886842:A:C	F933C	0.966
17:64886866:A:C	I925R	0.964

dbSNP variants (sampled 300 via entrez): RS1000011529 (17:64870219 T>G), RS1000093129 (17:45566458 A>C,G), RS1000097939 (17:64856985 A>G), RS1000144805 (17:45524875 A>T), RS1000150568 (17:45571495 C>T), RS1000183580 (17:45571796 A>C), RS1000234686 (17:64876803 G>A), RS1000413266 (17:64883328 G>A), RS1000472242 (17:45561990 AT>A,ATT), RS1000516578 (17:45524232 A>C), RS1000526874 (17:64918948 G>C,T), RS1000538809 (17:64908685 G>A,T), RS1000563862 (17:45511272 C>A,T), RS1000590950 (17:64909204 T>C), RS1000697095 (17:64858590 G>A,C,T)

Disease associations

OMIM: gene MIM:616557 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003984_2	Parkinson’s disease	4.000000e-32
GCST003996_26	Monobrow	3.000000e-32
GCST003998_7	Joint mobility (Beighton score)	6.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0007905	joint hypermobility measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Estradiol	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	increases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cadmium	increases abundance, decreases expression	1
Coal	decreases expression, increases abundance	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Mycophenolic Acid	decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer