PLS3

plastin 3, the group of EF-hand domain containing

Basic information

Region (hg38): X:115561173-115650861

Links

ENSG00000102024 ∙ NCBI:5358 ∙ OMIM:300131 ∙ HGNC:9091 ∙ Uniprot:P13797 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked osteoporosis with fractures (Supportive), mode of inheritance: XL
• X-linked osteoporosis with fractures (Strong), mode of inheritance: XL
• X-linked osteoporosis with fractures (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diaphragmatic hernia 5, X-linked	XL	Cardiovascular	Among other features, the condition can include cardiovascular anomalies, and awareness may allow early diagnosis and management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary	24088043; 37751738
Variants may also act as susceptibility factors related to osteoporosis, fractures, and related phenotypes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLS3 gene.

• not provided (142 variants)
• Bone mineral density quantitative trait locus 18 (10 variants)
• Inborn genetic diseases (10 variants)
• not specified (8 variants)
• Osteogenesis imperfecta (7 variants)
• Postmenopausal osteoporosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLS3 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				11	15	26
missense		1	42	3	3	49
nonsense	4					4
start loss						0
frameshift	8	3				11
inframe indel						0
splice donor/acceptor (+/-2bp)	3	3				6
splice region		1	1	6	2	10
non coding				25	29	54
Total	15	7	42	39	47

Variants in PLS3

This is a list of pathogenic ClinVar variants found in the PLS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-115610104-G-A			Likely benign (Jul 11, 2018)
X-115610165-C-T			Benign (Jul 07, 2018)
X-115610223-C-T		not specified	Benign (Nov 01, 2017)
X-115610265-T-C			Likely benign (Jan 10, 2024)
X-115610289-G-A			Likely benign (Oct 19, 2022)
X-115610306-A-G		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
X-115610331-T-A			Likely benign (Apr 12, 2022)
X-115610487-CT-C			Likely benign (Aug 13, 2020)
X-115610600-G-T			Benign (Jul 07, 2018)
X-115610944-C-A			Likely benign (Jun 19, 2018)
X-115622010-A-G			Benign (Jul 07, 2018)
X-115622116-T-A			Benign (Aug 14, 2018)
X-115622167-A-G			Benign (Jul 07, 2018)
X-115622196-C-A			Benign (Jul 07, 2018)
X-115622246-A-AT			Likely pathogenic (Oct 09, 2019)
X-115622249-T-C		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
X-115622258-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (May 05, 2023)
X-115622259-C-T			Benign (Jul 12, 2022)
X-115622261-G-A		Osteogenesis imperfecta	Uncertain significance (Sep 03, 2022)
X-115622304-T-G			Benign (May 28, 2022)
X-115622317-C-T			Uncertain significance (Mar 17, 2023)
X-115622360-A-G		Osteogenesis imperfecta	Uncertain significance (Jan 01, 2020)
X-115622363-G-A			Uncertain significance (Nov 06, 2023)
X-115622366-A-C			Uncertain significance (Jul 20, 2023)
X-115622386-ATAAG-A		Bone mineral density quantitative trait locus 18	Pathogenic (Mar 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLS3	protein_coding	protein_coding	ENST00000420625	15	89681

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.988	0.0116	120604	0	3	120607	0.0000124

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.71	109	223	0.489	0.0000158	4203
Missense in Polyphen		32	99.661	0.32109		1880
Synonymous	-0.553	88	81.6	1.08	0.00000623	1134
Loss of Function	3.98	2	22.3	0.0898	0.00000164	418

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000156	0.000124
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000131	0.00000898
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Actin-bundling protein found in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia. May play a role in the regulation of bone development.
• Disease: DISEASE: Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. {ECO:0000269|PubMed:24088043}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.649

Intolerance Scores

• loftool: 0.0349
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.977
• hipred: Y
• hipred_score: 0.768
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.730

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pls3
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: pls3
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: actin filament bundle assembly;actin filament network formation;bone development
• Cellular component: cytoplasm;cytosol;actin filament;plasma membrane;actin filament bundle
• Molecular function: calcium ion binding;actin filament binding