PDLIM5

protein-coding

PDZ and LIM domain 5, the group of LIM domain containing|PDZ domain containing

Gene summary

This gene encodes a member of a family of proteins that possess a 100-amino acid PDZ domain at the N terminus and one to three LIM domains at the C-terminus. This family member functions as a scaffold protein that tethers protein kinases to the Z-disk in striated muscles. It is thought to function in cardiomyocyte expansion and in restraining postsynaptic growth of excitatory synapses. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

MANE transcript

NM_006457.5

Inheritance

—

ClinVar variants

U:96B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr4:94,451,857-94,668,227

External References & Databases

Ensembl (ENSG00000163110)

Transcript & Mutation Effects

hg38 • Region Span ~216.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDLIM5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006457.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	1 clinvar	4
missense			82 clinvar	4 clinvar		86
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	96	5	1	102

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 153 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006457.5	RefSeq	NP_006448.5	12	MANE Select
ENST00000317968.9	Ensembl	ENSP00000321746.4	12	MANE Select
NM_001011513.4	RefSeq	NP_001011513.4	12	Standard
NM_001011515.3	RefSeq	NP_001011515.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Neuronal System

Biological Process

regulation of synapse assembly
regulation of dendritic spine morphogenesis
cell growth involved in cardiac muscle cell development
cell-cell adhesion

Molecular Function

actin binding
protein kinase C binding
protein binding
actinin binding
metal ion binding

Cellular Component

cytosol
cell-cell adherens junction
postsynaptic density
actin cytoskeleton
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000514743
Coding exons: 16
Length: 216341
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125745
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.679	294	329	0.895	0.0000168	4043
Missense (PolyPhen)		101	132.68	0.76123		1653
Synonymous	1.12	102	117	0.868	0.00000626	1222
Loss of Function	3.55	11	33.0	0.334	0.00000164	414

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00014	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May restrain postsynaptic growth of excitatory synapses (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.852

Intolerance Scores

LoFtool: 0.681
RVIS EVS: 1.34
RVIS percentile EVS: 94.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.546

Gene Damage Prediction

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