PLS3

plastin 3, the group of EF-hand domain containing

Basic information

Region (hg38): X:115561174-115650861

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
X-linked osteoporosis with fractures (Definitive), mode of inheritance: XL
hernia, anterior diaphragmatic (Moderate), 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 (198 variants)
Inborn_genetic_diseases (34 variants)
Bone_mineral_density_quantitative_trait_locus_18 (16 variants)
Hernia,_anterior_diaphragmatic (8 variants)
Osteogenesis_imperfecta (6 variants)
PLS3-related_disorder (6 variants)
not_specified (5 variants)
Congenital_diaphragmatic_hernia (2 variants)
Postmenopausal_osteoporosis (1 variants)
X-linked_osteoporosis_with_fractures (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. These statistics are base on transcript: NM_000005032.7. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	32 clinvar	17 clinvar	51
missense	2 clinvar	4 clinvar	80 clinvar	8 clinvar		94
nonsense	8 clinvar	1 clinvar	1 clinvar			10
start loss						0
frameshift	17 clinvar	5 clinvar	1 clinvar			23
splice donor/acceptor (+/-2bp)	5 clinvar	5 clinvar				10
Total	32	15	84	40	17

Highest pathogenic variant AF is 0.00000102516

Loading clinvar variants...

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