LRRC32

leucine rich repeat containing 32

Basic information

Region (hg38): 11:76657524-76670747

Previous symbols: [ "D11S833E", "GARP" ]

Links

ENSG00000137507 ∙ NCBI:2615 ∙ OMIM:137207 ∙ HGNC:4161 ∙ Uniprot:Q14392 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cleft palate, proliferative retinopathy, and developmental delay (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cleft palate, proliferative retinopathy, and developmental delay	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic	30976112

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRRC32 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRRC32 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	1	8
missense			52	5	1	58
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	52	12	3

Variants in LRRC32

This is a list of pathogenic ClinVar variants found in the LRRC32 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-76657978-G-A			Benign (May 01, 2023)
11-76659617-T-G		not specified	Uncertain significance (Feb 10, 2022)
11-76659635-C-T		not specified	Uncertain significance (Jun 16, 2023)
11-76659650-C-G		not specified	Uncertain significance (Apr 18, 2024)
11-76659747-C-T		not specified	Uncertain significance (Apr 29, 2024)
11-76659813-C-T		not specified	Uncertain significance (Mar 01, 2023)
11-76659819-C-T		not specified	Uncertain significance (Jan 21, 2022)
11-76659827-C-T		not specified	Uncertain significance (May 03, 2023)
11-76659828-G-C		not specified	Uncertain significance (Apr 20, 2024)
11-76659845-G-A		not specified	Uncertain significance (Mar 16, 2024)
11-76659865-G-A			Likely benign (Apr 01, 2023)
11-76659874-G-A			Likely benign (May 01, 2023)
11-76659902-C-T		not specified	Uncertain significance (Aug 28, 2023)
11-76659963-G-A		Global developmental delay;Vitreoretinopathy;Cleft palate • Cleft palate, proliferative retinopathy, and developmental delay	Pathogenic/Likely pathogenic (Oct 28, 2020)
11-76660002-C-A		not specified	Uncertain significance (Jun 24, 2022)
11-76660026-C-T		not specified	Uncertain significance (Apr 07, 2022)
11-76660034-T-C		not specified	Uncertain significance (Aug 12, 2021)
11-76660038-G-A		not specified	Uncertain significance (Aug 09, 2021)
11-76660040-C-T		LRRC32-related disorder	Likely benign (May 04, 2023)
11-76660042-C-A		not specified	Uncertain significance (Jun 05, 2023)
11-76660079-A-T		not specified	Uncertain significance (May 11, 2022)
11-76660081-C-A		not specified	Uncertain significance (Apr 25, 2023)
11-76660083-T-C		not specified	Uncertain significance (Mar 20, 2023)
11-76660089-C-T		not specified	Uncertain significance (Dec 16, 2023)
11-76660092-T-C		not specified	Uncertain significance (May 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRRC32	protein_coding	protein_coding	ENST00000407242	2	13224

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00108	0.956	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0889	393	398	0.987	0.0000256	4202
Missense in Polyphen		68	91.561	0.74267		1261
Synonymous	-1.17	210	190	1.11	0.0000117	1526
Loss of Function	1.78	7	14.3	0.491	7.74e-7	148

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000371	0.000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000557	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000644	0.0000615
Middle Eastern	0.0000557	0.0000544
South Asian	0.0000657	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:19750484, PubMed:19651619, PubMed:22278742). 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 (PubMed:22278742). Able to outcompete LTBP1 for binding to LAP regulatory chain of TGF-beta (PubMed:22278742). Controls activation of TGF-beta-1 (TGFB1) on the surface of activated regulatory T-cells (Tregs) (PubMed:19750484, PubMed:19651619). Required for epithelial fusion during palate development by regulating activation of TGF-beta-3 (TGFB3) (By similarity). {ECO:0000250|UniProtKB:G3XA59, ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:22278742}.

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.414
• rvis_EVS: -1.21
• rvis_percentile_EVS: 5.68

Haploinsufficiency Scores

• pHI: 0.210
• hipred: N
• hipred_score: 0.234
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.412

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lrrc32
• Phenotype: hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: lrrc32
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: distributed

Gene ontology

• Biological process: transforming growth factor beta receptor signaling pathway;positive regulation of gene expression;negative regulation of activated T cell proliferation;negative regulation of cytokine secretion;secondary palate development;regulation of transforming growth factor beta activation;regulation of transforming growth factor beta3 activation
• Cellular component: extracellular space;nucleoplasm;integral component of plasma membrane;cell surface;extracellular matrix
• Molecular function: protein binding;transforming growth factor beta binding