PDLIM4

protein-coding

PDZ and LIM domain 4, the group of LIM domain containing|PDZ domain containing

Gene summary

Enables alpha-actinin binding activity; protein homodimerization activity; and protein phosphatase binding activity. Involved in actin cytoskeleton organization. Located in several cellular components, including lamellipodium; perinuclear region of cytoplasm; and stress fiber. Part of filamentous actin. Implicated in osteoporosis. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_003687.4

Inheritance

—

ClinVar variants

U:33B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr5:132,257,696-132,273,454

External References & Databases

Ensembl (ENSG00000131435)

Transcript & Mutation Effects

hg38 • Region Span ~15.8 kb

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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 PDLIM4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003687.4. 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				3 clinvar		3
missense			33 clinvar	1 clinvar		34
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	4	0	37

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003687.4	RefSeq	NP_003678.2	7	MANE Select
ENST00000253754.8	Ensembl	ENSP00000253754.3	7	MANE Select
NM_001131027.2	RefSeq	NP_001124499.1	6	Standard
ENST00000379018.7	Ensembl	ENSP00000368303.3	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1

Biological Process

actin cytoskeleton reorganization
excitatory chemical synaptic transmission

Molecular Function

protein binding
protein phosphatase binding
protein homodimerization activity
metal ion binding
alpha-actinin binding

Cellular Component

stress fiber
nucleus
cytoplasm
cytoskeleton
lamellipodium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253754
Coding exons: 7
Length: 15784
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125680
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.715	186	216	0.863	0.0000149	2104
Missense (PolyPhen)		67	85.671	0.78206		888
Synonymous	0.530	86	92.5	0.930	0.00000699	684
Loss of Function	3.26	0	12.4	0.00	5.27e-7	150

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000046	0.000044	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 1: Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle (PubMed:19307596). Involved in reorganization of the actin cytoskeleton (PubMed:21636573). In nonmuscle cells, binds to ACTN1 (alpha- actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity). {ECO:0000250|UniProtKB:P36202, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:21636573}.;

Recessive Scores

pRec: 0.312

Intolerance Scores

RVIS EVS: 0.53
RVIS percentile EVS: 80.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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