GeneBe

PLS3

protein-coding

plastin 3, the group of EF-hand domain containing

Gene summary

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). The C-terminal 570 amino acids of the T-plastin and L-plastin proteins are 83% identical. It contains a potential calcium-binding site near the N terminus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

MANE transcript

NM_005032.7

Inheritance

XL

ClinVar variants

P:53U:225B:67

Top phenotype

Diaphragmatic hernia 5, X-linked

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chrX:115,561,174-115,650,861

External References & Databases

Ensembl (ENSG00000102024)NCBI Gene (5358)OMIM (300131)HGNC:9091GenCCUniProt (P13797)AlphaFoldClinVar (PLS3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~89.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hernia, anterior diaphragmaticMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010606

Submitter: Baylor College of Medicine Research Center

X-linked osteoporosis with fracturesDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0018315

Submitter: Ambry Genetics

X-linked osteoporosis with fracturesSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0018315

Submitter: Orphanet

X-linked osteoporosis with fracturesSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0018315

Submitter: PanelApp Australia

X-linked osteoporosis with fracturesDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0018315

Submitter: G2P

hernia, anterior diaphragmaticSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010606

Submitter: PanelApp Australia

X-linked osteoporosis with fracturesSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0018315

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Diaphragmatic hernia 5, X-linkedXL

Manifestation: Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary

Intervention: Cardiovascular

Rationale: Among other features, the condition can include cardiovascular anomalies, and awareness may allow early diagnosis and management

Comments: Variants may also act as susceptibility factors related to osteoporosis, fractures, and related phenotypes

Refs: 24088043; 37751738Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLS3 variants in ClinVar

10 Conditions Cataloged
not providedTotal: 230
Inborn genetic diseasesTotal: 38
not specifiedTotal: 26
Bone mineral density quantitative trait locus 18Total: 20
PLS3-related disorderTotal: 20
Hernia, anterior diaphragmaticTotal: 8
Osteogenesis imperfectaTotal: 6
Congenital diaphragmatic herniaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005032.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
22
clinvar
44
clinvar
15
clinvar
 81
missense
4
clinvar
156
clinvar
8
clinvar
 168
nonsense
8
clinvar
3
clinvar
7
clinvar
 18
start loss
0
frameshift
16
clinvar
8
clinvar
1
clinvar
 25
splice donor/acceptor (+/-2bp)
6
clinvar
8
clinvar
39
clinvar
 53
Total30232255215345

Highest pathogenic variant AF is 0.0000010251626

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 116 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005032.7RefSeqNP_005023.215MANE Select
ENST00000355899.8EnsemblENSP00000348163.315MANE Select
NM_001136025.5RefSeqNP_001129497.115Standard
NM_001172335.3RefSeqNP_001165806.115Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
pls3Danio rerio

Structure: motor neuron

Quality: increased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • actin filament bundle assembly
  • actin filament network formation
  • bone development

Molecular Function

  • calcium ion binding
  • actin filament binding

Cellular Component

  • cytoplasm
  • cytosol
  • actin filament
  • plasma membrane
  • actin filament bundle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000420625
Coding exons
15
Length
89681
Individuals with no LoFs
120604
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
120607
p
0.0000124
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.711092230.4890.00001584203
Missense (PolyPhen)3299.6610.321091880
Synonymous-0.5538881.61.080.000006231134
Loss of Function3.98222.30.08980.00000164418

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000160.00012rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000130.0000090rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.730

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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