LRRC32

Summary

LRRC32 (leucine rich repeat containing 32, HGNC:4161) is a protein-coding gene on chromosome 11q13.5, encoding Transforming growth factor beta activator LRRC32 (Q14392). Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.

This gene encodes a type I membrane protein which contains 20 leucine-rich repeats. Alterations in the chromosomal region 11q13-11q14 are involved in several pathologies.

Source: NCBI Gene 2615 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cleft palate, proliferative retinopathy, and developmental delay (Strong, GenCC)
• GWAS associations: 57
• Clinical variants (ClinVar): 155 total — 2 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_001128922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4161
Approved symbol	LRRC32
Name	leucine rich repeat containing 32
Location	11q13.5
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137507
Ensembl biotype	protein_coding
OMIM	137207
Entrez	2615

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000260061, ENST00000404995, ENST00000407242, ENST00000421973, ENST00000464145, ENST00000858024, ENST00000858025, ENST00000957909, ENST00000957910, ENST00000957911, ENST00000957912

RefSeq mRNA: 7 — MANE Select: NM_001128922 NM_001128922, NM_001370187, NM_001370188, NM_001370189, NM_001370190, NM_001370191, NM_005512

CCDS: CCDS8245

Canonical transcript exons

ENST00000260061 — 3 exons

Exon	Start	End
ENSE00001376179	76665871	76665958
ENSE00001401561	76670614	76670747
ENSE00001887729	76657524	76661508

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 98.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2600 / max 220.6199, expressed in 936 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121406	8.8232	883
121401	1.6805	491
121402	0.7041	321
121405	0.6837	362
121404	0.2655	146
121403	0.1029	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	98.44	gold quality
left coronary artery	UBERON:0001626	97.08	gold quality
right lung	UBERON:0002167	96.82	gold quality
upper lobe of left lung	UBERON:0008952	96.80	gold quality
metanephros cortex	UBERON:0010533	96.77	gold quality
omental fat pad	UBERON:0010414	96.31	gold quality
upper lobe of lung	UBERON:0008948	96.25	gold quality
peritoneum	UBERON:0002358	96.19	gold quality
coronary artery	UBERON:0001621	95.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.65	gold quality
descending thoracic aorta	UBERON:0002345	95.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.48	gold quality
endocervix	UBERON:0000458	95.43	gold quality
ascending aorta	UBERON:0001496	95.42	gold quality
thoracic aorta	UBERON:0001515	95.39	gold quality
right lobe of thyroid gland	UBERON:0001119	95.18	gold quality
aorta	UBERON:0000947	94.99	gold quality
tibial artery	UBERON:0007610	94.98	gold quality
popliteal artery	UBERON:0002250	94.94	gold quality
peripheral nervous system	UBERON:0000010	94.82	gold quality
tibial nerve	UBERON:0001323	94.82	gold quality
apex of heart	UBERON:0002098	94.56	gold quality
ectocervix	UBERON:0012249	93.99	gold quality
left uterine tube	UBERON:0001303	93.95	gold quality
left lobe of thyroid gland	UBERON:0001120	93.89	gold quality
right atrium auricular region	UBERON:0006631	93.41	gold quality
gall bladder	UBERON:0002110	93.37	gold quality
left adrenal gland cortex	UBERON:0035825	93.29	gold quality
mucosa of stomach	UBERON:0001199	93.28	gold quality
left adrenal gland	UBERON:0001234	93.24	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	54.41
E-HCAD-10	yes	33.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting LRRC32, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 40)

• GARP is a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression (PMID:18628982)
• GARP is a key receptor controlling FOXP3 in T(reg) cells following T-cell activation in a positive feedback loop assisted by LGALS3 and LGMN (PMID:19453521)
• Platelets and activated Tregs co-express latent TGF-beta and GARP on their membranes. (PMID:19651619)
• Expression of GARP on activated regulatory T cells correlates with their suppressive capacity. (PMID:19666573)
• Data show that latent TGF-beta, i.e. both LAP and mature TGF-beta, binds to GARP, which is present on the surface of stimulated Treg clones but not on Th clones. (PMID:19750484)
• the processing and expression of LRRC32 (PMID:21615933)
• on chromosome 11q13.5 near the leucine-rich repeat containing 32 gene (LRRC32, also known as GARP) associated with asthma risk (PMID:21907864)
• There are 2 independent signals, one in C11orf30 and the other in LRRC32, that are strongly associated with serum IgE levels. C11orf30-LRRC32 region may represent a common locus for atopic diseases via pathways involved in regulation of serum IgE levels (PMID:22070912)
• Findings support the idea that GARP is a new latent TGFbeta-binding protein that regulates the bioavailability of TGFbeta and provides a cell surface platform for alphaV integrin-dependent TGFbeta activation. (PMID:22278742)
• we investigated in detail miR-142-3 pregulation of GARP expression in regulatory CD25(+) CD4 T cells (PMID:23650616)
• GARP is regulated by miRNAs and controls latent TGF-beta1 production by human regulatory T cells. (PMID:24098777)
• GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. (PMID:26357016)
• since GARP functions as a transporter of transforming growth factor beta (TGFbeta), a cytokine with broad pleiotropic traits, GARP transcriptional attenuation by alternative promoters might provide a mechanism regulating peripheral TGFb (PMID:26584734)
• High GARP expression is associated with pancreatic cancer and liver metastases from colorectal cancer. (PMID:26885615)
• GARP is a surface molecule of regulatory T cells with roles in the regulatory function and TGF-beta releasing [review] (PMID:27095576)
• Data show that the Treg activation marker GARP (glycoprotein A repetitions predominant) is expressed on primary melanoma. (PMID:27248166)
• GARP plays an important role in the pathogenesis of atopic dermatitis. (PMID:27884290)
• these results define the oncogenic effects of the GARP-TGFbeta axis in the tumor microenvironment (PMID:27913437)
• LRRC32 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• CD4(+) CD25(+) GARP(+) Treg cells are defective in dilated cardiomyopathy patients and GARP seems to be a better molecular definition of the regulatory phenotype. (PMID:28207945)
• study showed that stimulated, human B lymphocytes produce active TGF-beta1 from surface GARP/latent TGF-beta1 complexes with isotype switching to IgA production. (PMID:28607112)
• This review summarizes the most important features of GARP biology described to date including gene regulation, protein expression and mechanism in activating latent TGF-beta, and the function of GARP in regulatory T cell biology and peripheral tolerance, as well as GARP’s increasingly recognized roles in platelet-mediated cancer immune evasion. [review] (PMID:29458436)
• Study demonstrated that B cells are required for the induction of oral tolerance of T cell-dependent antigens via GARP and revealed for the first time that cell surface GARP-TGF-beta is an important checkpoint for regulating B cell peripheral tolerance, highlighting a mechanism of autoimmune disease pathogenesis. (PMID:29618665)
• This finding reveals how GARP exploits an unusual medley of interactions, including fold complementation by the amino terminus of TGF-beta1, to chaperone and orient the cytokine for binding and activation by alphaVbeta8. (PMID:30361387)
• Increased GARP expression in papillary thyroid cancer was positively correlated with increased expression of Foxp3, which is very important for development of Tregs. But, there is no significant association of elevated expression of GARP with lymph node metastasis in papillary thyroid cancer. (PMID:30443770)
• Data indicate homozygous stop-gain variant in leucine rich repeat containing 32 protein (LRRC32) (c.1630C>T; p.(Arg544Ter)) as a candidate disease-associated gene in two families with developmental delay, cleft palate, and proliferative retinopathy. (PMID:30976112)
• Novel biomarkers for primary biliary cholangitis to improve diagnosis and understand underlying regulatory mechanisms. (PMID:31033124)
• Our findings reveal that GARP, as an immunoregulatory molecule, is located on, as well as in, tumor cells of GB and low-grade glioma, inhibiting effector T cell function, and thus contributing to the immunosuppressive tumor microenvironment of primary brain tumors. (PMID:31357555)
• Genetic variants of the C11orf30-LRRC32 region are associated with childhood asthma in the Chinese population. (PMID:31812328)
• Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-beta. (PMID:31915300)
• The Parkinson’s Disease Protein LRRK2 Interacts with the GARP Complex to Promote Retrograde Transport to the trans-Golgi Network. (PMID:32375042)
• GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-beta. (PMID:33203838)
• Expression of Leucine-rich Repeat-containing Protein 32 Following Lymphocyte Stimulation in Patients with Non-IgE-mediated Gastrointestinal Food Allergies. (PMID:33380925)
• Dysregulated immunity in PID patients with low GARP expression on Tregs due to mutations in LRRC32. (PMID:34059789)
• Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells. (PMID:34235533)
• GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer. (PMID:34421887)
• New insight into GARP striking role in cancer progression: application for cancer therapy. (PMID:36460874)
• Analysis of LAP[+] and GARP[+] Treg subsets in peripheral blood of patients with neuromyelitis optica spectrum disorders. (PMID:36683084)
• GARP on hepatic stellate cells is essential for the development of liver fibrosis. (PMID:37348791)
• Suppression of lysosome metabolism-meditated GARP/TGF-beta1 complexes specifically depletes regulatory T cells to inhibit breast cancer metastasis. (PMID:38698265)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc32	ENSMUSG00000090958
rattus_norvegicus	Lrrc32	ENSRNOG00000015310

Paralogs (22): IGFALS (ENSG00000099769), TLR8 (ENSG00000101916), LRRC17 (ENSG00000128606), RXFP2 (ENSG00000133105), CD180 (ENSG00000134061), TLR4 (ENSG00000136869), TLR2 (ENSG00000137462), LRRC3 (ENSG00000160233), LRRC53 (ENSG00000162621), TLR3 (ENSG00000164342), VASN (ENSG00000168140), RXFP1 (ENSG00000171509), NRROS (ENSG00000174004), TLR10 (ENSG00000174123), TLR1 (ENSG00000174125), TLR6 (ENSG00000174130), LRRC3B (ENSG00000179796), TSKU (ENSG00000182704), TLR5 (ENSG00000187554), TLR7 (ENSG00000196664), LRIT2 (ENSG00000204033), LRRC3C (ENSG00000204913)

Protein

Protein identifiers

Transforming growth factor beta activator LRRC32 — Q14392 (reviewed: Q14392)

Alternative names: Garpin, Glycoprotein A repetitions predominant, Leucine-rich repeat-containing protein 32

All UniProt accessions (2): Q14392, C9JYU3

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta. Able to outcompete LTBP1 for binding to LAP regulatory chain of TGF-beta. Controls activation of TGF-beta-1 (TGFB1) on the surface of activated regulatory T-cells (Tregs). Required for epithelial fusion during palate development by regulating activation of TGF-beta-3 (TGFB3).

Subunit / interactions. Interacts with TGFB1; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1, leading to regulate activation of TGF-beta-1. Interacts with TGFB2. Interacts with TGFB3; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB3, leading to regulate activation of TGF-beta-3. Interacts with LAPTM4B; decreases TGFB1 production in regulatory T-cells.

Subcellular location. Cell membrane. Cell surface.

Tissue specificity. Preferentially expressed in regulatory T-cells (Tregs).

Disease relevance. Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) [MIM:619074] An autosomal recessive disorder characterized by mild to severe intellectual disability with delayed or absent speech, hypotonia, cleft palate, proliferative retinopathy, and combined sensorineural and conductive hearing loss. Brain imaging shows ventriculomegaly, widened subarachnoid spaces, partial agenesis of the corpus callosum, hypoplastic cerebellar vermis, and Dandy Walker malformation. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the LRRC32/LRRC33 family.

RefSeq proteins (7): NP_001122394, NP_001357116, NP_001357117, NP_001357118, NP_001357119, NP_001357120, NP_005503 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF01462, PF13855

UniProt features (96 total): strand 36, repeat 20, turn 11, helix 9, glycosylation site 5, sequence variant 3, mutagenesis site 3, topological domain 2, domain 2, disulfide bond 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8C7H	ELECTRON MICROSCOPY	2.7
8VSB	ELECTRON MICROSCOPY	2.93
8REW	ELECTRON MICROSCOPY	2.98
8VSC	ELECTRON MICROSCOPY	3
6GFF	X-RAY DIFFRACTION	3.1
8VSD	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14392-F1	86.48	0.62

Antibody-complex structures (SAbDab): 3 — 6GFF, 8C7H, 8REW

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 (2): 211, 350

Glycosylation sites (5): 203, 271, 308, 345, 545

Mutagenesis-validated functional residues (3):

Position	Phenotype
211	abolishes interaction with latency-associated peptide (lap) of tgfb1; when associated with a-350.
350	abolishes interaction with latency-associated peptide (lap) of tgfb1; when associated with a-211.
436	abolishes cell surface localization without affecting interaction with latency-associated peptide (lap) of tgfb1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 239 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, MODULE_64, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, chr11q13, GOBP_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_LEUKOCYTE_PROLIFERATION, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA

GO Biological Process (7): negative regulation of cytokine production (GO:0001818), transforming growth factor beta receptor signaling pathway (GO:0007179), positive regulation of gene expression (GO:0010628), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), establishment of protein localization to extracellular region (GO:0035592), negative regulation of activated T cell proliferation (GO:0046007), secondary palate development (GO:0062009)

GO Molecular Function (5): signaling receptor activity (GO:0038023), transforming growth factor beta binding (GO:0050431), receptor ligand inhibitor activity (GO:0141069), protein binding (GO:0005515), growth factor binding (GO:0019838)

GO Cellular Component (4): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
establishment of protein localization	1
negative regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
roof of mouth development	1
molecular transducer activity	1
growth factor binding	1
cytokine binding	1
receptor ligand activity	1
molecular function inhibitor activity	1
binding	1
protein binding	1
nuclear lumen	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC32	TGFB1	P01137	913
LRRC32	TGFB3	P10600	802
LRRC32	TGFB2	P08112	783
LRRC32	EMSY	Q7Z589	725
LRRC32	FOXP3	Q9BZS1	595
LRRC32	WDR36	Q8NI36	591
LRRC32	NRP1	O14786	572
LRRC32	IKZF4	Q9H2S9	503
LRRC32	CAPN14	A8MX76	497
LRRC32	CD4	P01730	480
LRRC32	TNFRSF18	Q9Y5U5	450
LRRC32	CTLA4	P16410	447
LRRC32	IKZF2	Q9UKS7	446
LRRC32	ENTPD1	P49961	445
LRRC32	THBS1	P07996	442

IntAct

10 interactions, top by confidence:

A	B	Type	Score
TGFB1	LRRC32	psi-mi:“MI:0915”(physical association)	0.850
TGFB1	LRRC32	psi-mi:“MI:0407”(direct interaction)	0.850
LRRC32	SMPD2	psi-mi:“MI:0914”(association)	0.640
CBFB	RP2	psi-mi:“MI:0914”(association)	0.350
LRRC32	ORC4	psi-mi:“MI:0914”(association)	0.350
SPG21	LRRC32	psi-mi:“MI:0914”(association)	0.350

BioGRID (35): LRRC32 (Synthetic Lethality), ZDHHC6 (Affinity Capture-MS), TGFB1 (Affinity Capture-MS), STAT3 (Affinity Capture-MS), DCP2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SLC16A10 (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), STK11IP (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), HLA-C (Affinity Capture-MS), STK11IP (Affinity Capture-MS), SLC16A10 (Affinity Capture-MS), TGFB1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A4IFA6, A6NDA9, E7FE13, G3XA59, O08644, O08742, O08770, O14498, O15197, P0C0K6, P0C0K7, P35590, P40197, P59383, Q06805, Q06806, Q14392, Q149C3, Q3ZBI5, Q5JZY3, Q5NVQ6, Q5R6B1, Q5RF01, Q5RKR3, Q6EMK4, Q6GU68, Q6P7C4, Q6PFC5, Q6QMY6, Q6UXK2, Q6UY18, Q80ZD5, Q86UE6, Q86WK7, Q86YC3, Q8BGX3, Q8BYG9, Q8C2S7, Q8CBR6

Diamond homologs: G3XA59, Q14392, Q3ZBI5, Q4R8Y9, Q5BK65, Q5RF01, Q6JN46, Q6PEZ8, Q86YC3, Q8BMT4, Q8CBR6, Q965M2, Q9CQ76, Q6P3Y9, Q7TQ62, Q7Z5L7, A8WHP9, P58727, Q6AXL3, Q9MYW3, Q6QMY6, A8WGA3, D4AC13, E5DHB5, F7D3V9, O35930, O46378, O46379, O77742, P19879, P51890, P58682, Q28256, Q52KR2, Q58A48, Q5M7S9, Q5TJ59, Q62000, Q65YW8, Q65Z91

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	116
Likely benign	24
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1330304	NM_001128922.2(LRRC32):c.980T>C (p.Ile327Thr)	Likely pathogenic
1676660	NM_001128922.2(LRRC32):c.84+14C>A	Likely pathogenic

SpliceAI

665 predictions. Top by Δscore:

Variant	Effect	Δscore
11:76665870:CCAT:C	donor_gain	0.9900
11:76670608:TCCTA:T	donor_loss	0.9900
11:76670609:CCTAC:C	donor_loss	0.9900
11:76670610:CTACC:C	donor_loss	0.9900
11:76670611:TA:T	donor_loss	0.9900
11:76670612:A:C	donor_loss	0.9900
11:76670613:C:CA	donor_loss	0.9900
11:76665959:C:CC	acceptor_gain	0.9800
11:76670613:CCTGG:C	donor_gain	0.9800
11:76665954:TGGCT:T	acceptor_gain	0.9700
11:76665957:CT:C	acceptor_gain	0.9700
11:76665957:CTCTG:C	acceptor_gain	0.9700
11:76665958:TCTGT:T	acceptor_gain	0.9700
11:76665961:G:C	acceptor_gain	0.9700
11:76665969:C:CT	acceptor_gain	0.9400
11:76670319:G:A	donor_gain	0.9200
11:76670324:G:C	donor_gain	0.9000
11:76670612:A:AC	donor_gain	0.9000
11:76670613:C:CC	donor_gain	0.9000
11:76664949:T:TA	donor_gain	0.8900
11:76665869:ACCAT:A	donor_gain	0.8900
11:76665870:CCATC:C	donor_gain	0.8900
11:76665956:GCT:G	acceptor_gain	0.8900
11:76661507:ACCTG:A	acceptor_loss	0.8800
11:76661510:T:A	acceptor_loss	0.8800
11:76665955:GGCT:G	acceptor_gain	0.8800
11:76665961:G:GC	acceptor_gain	0.8800
11:76665873:T:TA	donor_gain	0.8700
11:76665956:GCTCT:G	acceptor_loss	0.8600
11:76665957:CTCT:C	acceptor_loss	0.8600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000154886 (11:76668106 A>G), RS1000188933 (11:76664615 G>A), RS1000610097 (11:76667848 T>C), RS1000699215 (11:76670354 C>A), RS1000751103 (11:76670548 C>A,T), RS1000955040 (11:76658104 A>G), RS1001001303 (11:76664011 G>A), RS1001053622 (11:76663718 A>G), RS1001247571 (11:76666269 A>C), RS1001566204 (11:76669427 G>A,C), RS1001594088 (11:76666101 G>T), RS1001703857 (11:76671180 G>T), RS1001986955 (11:76665305 G>A), RS1002360374 (11:76661785 T>C,G), RS1002605221 (11:76670481 C>A)

Disease associations

OMIM: gene MIM:137207 | disease phenotypes: MIM:619074

GenCC curated gene-disease

Disease	Classification	Inheritance
cleft palate, proliferative retinopathy, and developmental delay	Strong	Autosomal recessive

Mondo (3): cleft palate, proliferative retinopathy, and developmental delay (MONDO:0033641), cleft palate (MONDO:0016064), vitreoretinal degeneration (MONDO:0020248)

Orphanet (2): Cleft palate (Orphanet:2014), OBSOLETE: Vitreoretinal degeneration (Orphanet:98670)

HPO phenotypes

21 total (22 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000322	Short philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000486	Strabismus
HP:0000545	Myopia
HP:0000750	Delayed speech and language development
HP:0001047	Atopic dermatitis
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001320	Cerebellar vermis hypoplasia
HP:0001338	Partial agenesis of the corpus callosum
HP:0001511	Intrauterine growth retardation
HP:0002119	Ventriculomegaly
HP:0002389	Cavum septum pellucidum
HP:0008936	Axial hypotonia
HP:0010535	Sleep apnea
HP:0011800	Midface retrusion
HP:0030666	Retinal neovascularization
HP:0031936	Delayed ability to walk
HP:0007964	Degenerative vitreoretinopathy

GWAS associations

57 associations (top):

Study	Trait	p-value
GCST001226_4	Asthma	2.000000e-08
GCST001303_1	IgE grass sensitization	1.000000e-08
GCST001310_4	Allergic rhinitis	4.000000e-08
GCST002083_26	Self-reported allergy	2.000000e-19
GCST002084_9	Allergic sensitization	1.000000e-18
GCST002100_4	Atopic dermatitis	4.000000e-13
GCST002527_8	Eosinophilic esophagitis	4.000000e-07
GCST003180_6	Atopic march	2.000000e-15
GCST003184_34	Atopic dermatitis	5.000000e-13
GCST003854_11	Gut microbiota (functional units)	1.000000e-07
GCST003854_14	Gut microbiota (functional units)	5.000000e-07
GCST003854_48	Gut microbiota (functional units)	3.000000e-06
GCST003854_50	Gut microbiota (functional units)	3.000000e-06
GCST003944_21	Hepcidin/ferritin ratio	3.000000e-06
GCST003987_7	Asthma	1.000000e-16
GCST003990_6	Allergy	1.000000e-14
GCST004861_1	Itch intensity from mosquito bite	2.000000e-09
GCST004866_9	Alopecia areata	4.000000e-08
GCST004979_1	Food allergy	9.000000e-11
GCST005038_132	Allergic disease (asthma, hay fever or eczema)	2.000000e-63
GCST005038_74	Allergic disease (asthma, hay fever or eczema)	2.000000e-40
GCST005038_75	Allergic disease (asthma, hay fever or eczema)	4.000000e-14
GCST005212_17	Asthma	2.000000e-14
GCST005975_19	Eosinophil count	1.000000e-08
GCST006198_1	Giant cell arteritis	4.000000e-06
GCST006409_37	Allergic rhinitis	7.000000e-24
GCST006862_15	Asthma	3.000000e-15
GCST007139_3	Shingles	2.000000e-09
GCST007797_1	Asthma onset (childhood vs adult)	6.000000e-19
GCST007797_12	Asthma onset (childhood vs adult)	5.000000e-17

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005298	allergic sensitization measurement
EFO:0007755	atopic march
EFO:0007874	gut microbiome measurement
EFO:0007901	hepcidin:ferritin ratio
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0007016	food allergy measurement
EFO:0004842	eosinophil count
EFO:0004847	age at onset
EFO:1002011	adult onset asthma
EFO:0009130	clostridium difficile infection

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Leucine-rich repeat proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
livmoniplimab	Binding	9.12	pKd

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
sodium arsenite	increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Nickel	increases expression	2
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
pentanal	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
incobotulinumtoxinA	increases expression	1
Aldehydes	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cytarabine	decreases expression	1
Dexamethasone	decreases expression	1
Doxorubicin	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases reaction	1
Methapyrilene	decreases methylation	1
Phenobarbital	affects expression	1
Progesterone	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2BI	HAP1 LRRC32 (-) 1	Cancer cell line	Male
CVCL_E2BJ	HAP1 LRRC32 (-) 2	Cancer cell line	Male
CVCL_E2BK	HAP1 LRRC32 (-) 3	Cancer cell line	Male
CVCL_E4J8	Genomeditech CHO-K1 H_LRRC32(GARP)	Spontaneously immortalized cell line	Female
CVCL_E4J9	Genomeditech HEK-293 H_LRRC32(GARP)	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT00760006	PHASE2	COMPLETED	Preventing Complications in Cleft Palate Repair With Antibiotics
NCT01760330	PHASE2	WITHDRAWN	IV Acetaminophen in Children Undergoing Palatoplasty
NCT02350803	PHASE2	COMPLETED	Does Use of Rigid Fixation After Removing Distraction Osteogenesis Device Reduce the Relapse?
NCT03412474	PHASE2	COMPLETED	Suprazygomatic Block in Cleft Palate Surgery in Children
NCT01616953	PHASE1/PHASE2	COMPLETED	Cell Therapy for Craniofacial Bone Defects
NCT02247193	PHASE1/PHASE2	COMPLETED	Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair
NCT00097149	Not specified	COMPLETED	Systematic Pediatric Care for Oral Clefts - South America
NCT00285714	Not specified	UNKNOWN	3D Imaging of Hard and Soft Tissue in Orthognathic Surgery
NCT00340977	Not specified	COMPLETED	Svangerskap, Arv, Og Miljo (Pregnancy, Heredity and Environment)
NCT00423072	Not specified	COMPLETED	Middle Ear Pressure Disregulation in Cleft Palate Patients
NCT00584272	Not specified	COMPLETED	Retrospective Study on the Outcome of Cleft Palate Repair: Comparing US Surgical and Ethicon Suture Materials
NCT00773994	Not specified	COMPLETED	Pilot Study Evaluating Characteristic Closure Patterns of the Normal Velopharyngeal Portal
NCT00779961	Not specified	UNKNOWN	An Investigation for the Optimal Timing of a Cleft Palate Repair
NCT00829101	Not specified	COMPLETED	Articulation and Phonology in Children With Unilateral Cleft Lip and Palate
NCT00993551	Not specified	COMPLETED	Timing of Primary Surgery for Cleft Palate
NCT00993993	Not specified	COMPLETED	Relational Development in Children With Cleft Lips and Palates: Influence of the Waiting Period Prior to the First Surgical Intervention and the Parents’ Psychological Perception of the Abnormality
NCT01046591	Not specified	COMPLETED	Sleep and Behavior in Children With Cleft Palate
NCT01252264	Not specified	COMPLETED	FaceBase Biorepository
NCT01380171	Not specified	COMPLETED	Primary Palatoplasty in Pediatric Patients - A Retrospective Review of Surgical Outcomes
NCT01500109	Not specified	COMPLETED	Efficacy of Oral Versus Intravenous Acetaminophen for Primary Pediatric Cleft Palate Repair
NCT01535131	Not specified	COMPLETED	Furlow Palatoplasty With Tensor Tenopexy
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01867632	Not specified	COMPLETED	Acellular Dermal Matrix in Primary Palatoplasty
NCT02329509	Not specified	COMPLETED	Evaluation of Facial Growth in Two Primary Protocols Used in the Surgical Treatment of Unilateral Cleft Lip and Palate Patients
NCT02415361	Not specified	COMPLETED	Follow Ups of Parents With Infants With Cleft Lip and Palate
NCT02583100	Not specified	COMPLETED	Improving Outcomes in Cleft Palate Surgery
NCT02595307	Not specified	UNKNOWN	Improving Informed Consent for Cleft Palate Repair
NCT02658318	Not specified	COMPLETED	Postoperative Complications After Cleft Palate Closure in Patients With Pierre Robin Sequence: Operative Considerations
NCT02688634	Not specified	WITHDRAWN	The Role of Antibiotic Prophylaxis in Cleft Palate and Velopharyngeal Insufficiency Repair
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)