PDLIM5

Summary

PDLIM5 (PDZ and LIM domain 5, HGNC:17468) is a protein-coding gene on chromosome 4q22.3, encoding PDZ and LIM domain protein 5 (Q96HC4). May play an important role in the heart development by scaffolding PKC to the Z-disk region.

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.

Source: NCBI Gene 10611 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 126 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006457

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17468
Approved symbol	PDLIM5
Name	PDZ and LIM domain 5
Location	4q22.3
Locus type	gene with protein product
Status	Approved
Aliases	LIM, Enh
Ensembl gene	ENSG00000163110
Ensembl biotype	protein_coding
OMIM	605904
Entrez	10611

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 31 protein_coding, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000317968, ENST00000318007, ENST00000359265, ENST00000380176, ENST00000380180, ENST00000437932, ENST00000503974, ENST00000504489, ENST00000506632, ENST00000508216, ENST00000508531, ENST00000509333, ENST00000509357, ENST00000510099, ENST00000511586, ENST00000511767, ENST00000512274, ENST00000513341, ENST00000514743, ENST00000514830, ENST00000542407, ENST00000615540, ENST00000627587, ENST00000863584, ENST00000863585, ENST00000863586, ENST00000863587, ENST00000863588, ENST00000968730, ENST00000968731, ENST00000968732, ENST00000968733, ENST00000968734, ENST00000968735, ENST00000968736, ENST00000968737, ENST00000968738, ENST00000968739, ENST00000968740, ENST00000968741

RefSeq mRNA: 9 — MANE Select: NM_006457 NM_001011513, NM_001011515, NM_001011516, NM_001256425, NM_001256426, NM_001256427, NM_001256428, NM_001256429, NM_006457

CCDS: CCDS3641, CCDS47102, CCDS47103, CCDS47104, CCDS58915, CCDS58916, CCDS58917, CCDS75166

Canonical transcript exons

ENST00000317968 — 13 exons

Exon	Start	End
ENSE00001484030	94451942	94451995
ENSE00001948294	94663978	94668223
ENSE00003510903	94657427	94657547
ENSE00003528515	94585565	94585737
ENSE00003569270	94654460	94654640
ENSE00003622744	94640276	94640450
ENSE00003637793	94523724	94523875
ENSE00003638649	94662422	94662537
ENSE00003644601	94573351	94573393
ENSE00003652664	94575616	94576034
ENSE00003653465	94586408	94586444
ENSE00003692320	94455247	94455384
ENSE00003715761	94618004	94618191

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.8652 / max 1777.9042, expressed in 1816 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48919	86.2222	1816
48924	0.9222	519
48943	0.4043	172
48923	0.1126	34
48922	0.0666	20
48926	0.0636	31
48918	0.0482	21
48921	0.0255	9

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	99.90	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.78	gold quality
heart right ventricle	UBERON:0002080	99.74	gold quality
triceps brachii	UBERON:0001509	99.62	gold quality
gluteal muscle	UBERON:0002000	99.61	gold quality
diaphragm	UBERON:0001103	99.58	gold quality
choroid plexus epithelium	UBERON:0003911	99.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.51	gold quality
blood vessel layer	UBERON:0004797	99.40	gold quality
gastrocnemius	UBERON:0001388	99.38	gold quality
muscle of leg	UBERON:0001383	99.31	gold quality
body of tongue	UBERON:0011876	99.31	gold quality
cardiac ventricle	UBERON:0002082	99.17	gold quality
heart left ventricle	UBERON:0002084	99.15	gold quality
muscle organ	UBERON:0001630	99.13	gold quality
right atrium auricular region	UBERON:0006631	99.11	gold quality
jejunal mucosa	UBERON:0000399	99.00	gold quality
skeletal muscle tissue	UBERON:0001134	98.90	gold quality
cauda epididymis	UBERON:0004360	98.86	gold quality
tongue squamous epithelium	UBERON:0006919	98.86	gold quality
saphenous vein	UBERON:0007318	98.83	gold quality
vastus lateralis	UBERON:0001379	98.82	gold quality
jejunum	UBERON:0002115	98.78	gold quality
heart	UBERON:0000948	98.73	gold quality
apex of heart	UBERON:0002098	98.73	gold quality
cardiac atrium	UBERON:0002081	98.60	gold quality
oral cavity	UBERON:0000167	98.59	gold quality
germinal epithelium of ovary	UBERON:0001304	98.48	gold quality
parietal pleura	UBERON:0002400	98.48	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	33.49
E-GEOD-93593	yes	19.27
E-HCAD-5	yes	13.93
E-CURD-119	yes	13.65
E-MTAB-9067	yes	11.28
E-GEOD-135922	yes	9.63
E-MTAB-11268	no	3480.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

236 targeting PDLIM5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959

Literature-anchored findings (GeneRIF, showing 27)

• Altered expression of LIM was found in brains and lymphoblastoid cells from patients with bipolar disorder. (PMID:14743183)
• It is confirmed a decreased expression of LIM in the lymphoblastoid cell lines from patients with bipolar I disorder and schizophrenia. (PMID:15362566)
• Western blot studies of muscle tissues revealed that ENH4 is present only in skeletal muscle and there is a specific distribution of ENH members between skeletal and cardiac muscles, which is different in human and mouse. (PMID:15555569)
• Genetic association study revealed the association of single nucleotide polymorphism (SNP)1 (rs10008257) with bipolar disorder. (PMID:16044170)
• ENH is a restraining factor of the oncogenic activity of inhibitor of DNA binding 2 proteins in neural tumors (PMID:16549780)
• Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant. (PMID:16595163)
• We suggest that the higher expression levels of the PDLIM5 mRNA in the peripheral leukocytes may be a candidate marker for medication-free schizophrenic patients. (PMID:17287082)
• our results provide further evidence to support PDLIM5 as a potential susceptible gene for schizophrenia (PMID:18021463)
• PDLIM5 gene is associated with recurrent major depressive disorder. (PMID:18197271)
• tested for an association between three single nucleotide polymorphisms at the PDLIM5 gene and lithium prophylaxis in a Sardinian sample comprised of 155 bipolar patients treated with lithium (PMID:18456508)
• PDLIM5 may have a minor effect on susceptibility to bipolar disorder in Caucasians. (PMID:18496208)
• The aim of this study was to investigate the association between PDLIM5 single nucleotide polymorphisms and bipolar disorder in a case-control sample. (PMID:18496210)
• Our results suggest that PDLIM5 might play a role in susceptibility to bipolar disorder among the Chinese Han population. (PMID:19448850)
• LIM domains have a novel molecular function: the regulation of PKC activities in a PKC isoform-specific manner. (PMID:21266195)
• PDLIM5 (rs17021918,T), SLC22A3 (rs9364554,C) and NKX3-1 (rs1512268,A) SNPs might not be associated with prostate cancer in Chinese men. (PMID:22741436)
• The significant difference in expression of PDLIM5 mRNA in the peripheral blood leukocytes of treatment-naive bipolar (BPD) patients versus that of healthy control subjects suggests that it may be a good biological marker for BPD. (PMID:23031404)
• It can be deduced that the nonsynonymous rs7690296 polymorphism of PDLIM5 could play an important role in the pathophysiology of both bipolar disorder and schizophrenia. (PMID:24064681)
• The study provides evidence of several genetic variants within the PDLIM5 gene and interactions between PDLIM5 and steroid use influencing cancer. (PMID:27350677)
• Findings provide evidence of shared genetic variants in PDLIM5 gene influencing alcohol dependence, type 2 diabetes, and hypertension. (PMID:27693979)
• this study shows functional importance of PDLIM5 for proper kAE1 membrane residency, as a crucial linker between kidneyAE1 and actin cytoskeleton-associated proteins in polarized cells (PMID:28045035)
• PDLIM5 was strongly up-regulated during cardiomyogenesis and novel stage-specific isoforms were detected for PDLIM5 (PMID:28139119)
• PDLIM5 promotes papillary thyroid carcinoma via activation of the Ras-ERK pathway. (PMID:29574154)
• Forces acting on integrins recruit Enigma family proteins (PDLIM5 AND PDLIM7) to trigger YAP activation during mechanotransduction. (PMID:30404826)
• Novel polymorphisms in PDLIM3 and PDLIM5 gene encoding Z-line proteins increase risk of idiopathic dilated cardiomyopathy. (PMID:31424159)
• Mutations in PDLIM5 are rare in dilated cardiomyopathy but are emerging as potential disease modifiers. (PMID:31880413)
• PDLIM5 inhibits STUB1-mediated degradation of SMAD3 and promotes the migration and invasion of lung cancer cells. (PMID:32737199)
• Mechanical Sensing Element PDLIM5 Promotes Osteogenesis of Human Fibroblasts by Affecting the Activity of Microfilaments. (PMID:34069539)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdlim5b	ENSDARG00000027600
danio_rerio	pdlim5a	ENSDARG00000101777
mus_musculus	Pdlim5	ENSMUSG00000028273
rattus_norvegicus	Pdlim5	ENSRNOG00000016419
drosophila_melanogaster	Zasp52	FBGN0265991
caenorhabditis_elegans		WBGENE00001132

Paralogs (7): PDLIM1 (ENSG00000107438), PDLIM2 (ENSG00000120913), LDB3 (ENSG00000122367), PDLIM4 (ENSG00000131435), PDLIM3 (ENSG00000154553), PDLIM7 (ENSG00000196923), PRICKLE4 (ENSG00000278224)

Protein

Protein identifiers

PDZ and LIM domain protein 5 — Q96HC4 (reviewed: Q96HC4)

Alternative names: Enigma homolog, Enigma-like PDZ and LIM domains protein

All UniProt accessions (9): A0A0A0MSP3, A0A0D9SFR4, A0A0D9SFW3, D6RAA1, D6RGG6, Q96HC4, H0Y8Y3, H0Y929, H0YBI4

UniProt curated annotations — full annotation on UniProt →

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. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation.

Subunit / interactions. Interacts with various PKC isoforms through the LIM domains. Interacts with actin and alpha-actinin through the PDZ domain. Interacts (via LIM domains) with SIPA1L1/SPAR; this interaction may occur preferentially with isoform 1.

Subcellular location. Postsynaptic density. Presynapse. Postsynapse. Cytoplasm. Cytosol.

Tissue specificity. Heart and skeletal muscle specific. Expression is commonly increased in the brain of patients with bipolar disorder, schizophrenia, and major depression.

Isoforms (7)

UniProt ID	Names	Canonical?
Q96HC4-1	1	yes
Q96HC4-2	2
Q96HC4-3	3
Q96HC4-4	4
Q96HC4-5	5
Q96HC4-6	6
Q96HC4-7	7

RefSeq proteins (9): NP_001011513, NP_001011515, NP_001011516, NP_001243354, NP_001243355, NP_001243356, NP_001243357, NP_001243358, NP_006448* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR001781	Znf_LIM	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR050604	PDZ-LIM_domain	Family

Pfam: PF00412, PF00595

UniProt features (69 total): modified residue 15, strand 12, splice variant 10, compositionally biased region 8, sequence variant 6, domain 4, helix 4, region of interest 4, turn 2, initiator methionine 1, chain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9F6S	X-RAY DIFFRACTION	1
2UZC	X-RAY DIFFRACTION	1.5
2DAR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HC4-F1	64.95	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (16): 2, 2, 89, 89, 111, 134, 137, 228, 260, 309, 313, 322, 350, 360, 362, 89

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins

MSigDB gene sets: 434 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_DENDRITE_DEVELOPMENT, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, LEE_NEURAL_CREST_STEM_CELL_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, GOZGIT_ESR1_TARGETS_DN, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH

GO Biological Process (7): heart development (GO:0007507), actin cytoskeleton organization (GO:0030036), regulation of synapse assembly (GO:0051963), regulation of dendritic spine morphogenesis (GO:0061001), cell growth involved in cardiac muscle cell development (GO:0061049), muscle structure development (GO:0061061), cell-cell adhesion (GO:0098609)

GO Molecular Function (7): actin binding (GO:0003779), protein kinase C binding (GO:0005080), actinin binding (GO:0042805), metal ion binding (GO:0046872), muscle alpha-actinin binding (GO:0051371), cadherin binding involved in cell-cell adhesion (GO:0098641), protein binding (GO:0005515)

GO Cellular Component (13): stress fiber (GO:0001725), cytosol (GO:0005829), adherens junction (GO:0005912), postsynaptic density (GO:0014069), actin cytoskeleton (GO:0015629), membrane (GO:0016020), Z disc (GO:0030018), filamentous actin (GO:0031941), presynapse (GO:0098793), cytoplasm (GO:0005737), cell projection (GO:0042995), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cytoskeletal protein binding	2
synapse	2
animal organ development	1
circulatory system development	1
cytoskeleton organization	1
actin filament-based process	1
synapse assembly	1
regulation of synapse organization	1
regulation of cell junction assembly	1
regulation of neuron projection development	1
regulation of anatomical structure morphogenesis	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
physiological cardiac muscle hypertrophy	1
developmental cell growth	1
cardiac muscle cell development	1
anatomical structure development	1
cell adhesion	1
protein kinase binding	1
cation binding	1
alpha-actinin binding	1
cadherin binding	1
cell-cell adhesion	1
cell-cell adhesion mediator activity	1
binding	1
actomyosin	1
contractile actin filament bundle	1
cytoplasm	1
cell-cell junction	1
asymmetric synapse	1
postsynaptic specialization	1
cytoskeleton	1
I band	1
actin filament	1
protein-containing complex	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

167 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
PDLIM7	BAG3	psi-mi:“MI:0914”(association)	0.800
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
PHF19	EED	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
COIL	PDLIM5	psi-mi:“MI:0915”(physical association)	0.670
PDLIM5	COIL	psi-mi:“MI:0915”(physical association)	0.670
PDLIM5	ID2	psi-mi:“MI:0915”(physical association)	0.630
ID2	PDLIM5	psi-mi:“MI:0915”(physical association)	0.630
PDLIM5	ID2	psi-mi:“MI:0407”(direct interaction)	0.630
KRTAP10-7	PDLIM5	psi-mi:“MI:0915”(physical association)	0.560
ZYX	PDLIM5	psi-mi:“MI:0915”(physical association)	0.560
PDLIM5	KRT40	psi-mi:“MI:0915”(physical association)	0.560
CCDC136	PDLIM5	psi-mi:“MI:0915”(physical association)	0.560
KRT40	PDLIM5	psi-mi:“MI:0915”(physical association)	0.560
PDLIM5	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
PDLIM5	ZYX	psi-mi:“MI:0915”(physical association)	0.560
PDLIM5	CCDC136	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (246): PDLIM5 (Two-hybrid), PDLIM5 (Two-hybrid), CCDC136 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), PDLIM5 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), TRIM39 (Two-hybrid), DNAJC8 (Co-fractionation)

ESM2 similar proteins: A0JMZ1, A1L209, A1L2F3, A1L3I5, A2AWT3, A4FUE7, A6QQM4, O82171, O94519, P97868, Q08AZ1, Q14CW9, Q1W1G1, Q22122, Q2HJG4, Q2YDJ0, Q32KN7, Q5EAW4, Q5PPV5, Q5REC0, Q5TFG8, Q5ZMS6, Q618K0, Q62920, Q64GL0, Q66HC1, Q6DGN6, Q6NRP6, Q6P1U3, Q6V5K9, Q7SXT7, Q7Z6E9, Q801E2, Q8BJH1, Q8CI51, Q8H100, Q8IMP6, Q8IYB5, Q8R550, Q91W18

Diamond homologs: A1ZA47, A2ALU4, A5H447, D4A702, E1BKA3, O00151, O14639, O43294, O60711, O70209, O70400, O75112, O94929, P20271, P48059, P49023, P49024, P50464, P52944, Q09476, Q0WSN2, Q13796, Q15942, Q1JQB5, Q2KJ33, Q2TCH4, Q2YDK0, Q3MHZ4, Q3SX26, Q3SX40, Q3SYZ8, Q3T0X8, Q3TJD7, Q55BI0, Q5F464, Q5R7I1, Q5RCF7, Q5TD97, Q5U2Z2, Q5XI07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

126 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	79
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1340302	GRCh37/hg19 4q22.3-25(chr4:95490755-109977216)x3	Likely pathogenic

SpliceAI

4567 predictions. Top by Δscore:

Variant	Effect	Δscore
4:94451994:AGGT:A	donor_loss	1.0000
4:94451996:GTG:G	donor_loss	1.0000
4:94452084:G:T	donor_gain	1.0000
4:94455243:ACAG:A	acceptor_loss	1.0000
4:94455244:C:G	acceptor_gain	1.0000
4:94455244:CAGC:C	acceptor_loss	1.0000
4:94455245:A:AG	acceptor_gain	1.0000
4:94455245:AG:A	acceptor_loss	1.0000
4:94455246:G:GG	acceptor_gain	1.0000
4:94455246:GC:G	acceptor_gain	1.0000
4:94455246:GCAT:G	acceptor_gain	1.0000
4:94455246:GCATA:G	acceptor_gain	1.0000
4:94455380:CTAGT:C	donor_gain	1.0000
4:94455383:GT:G	donor_gain	1.0000
4:94455385:G:GG	donor_gain	1.0000
4:94523721:CA:C	acceptor_loss	1.0000
4:94523722:A:AC	acceptor_loss	1.0000
4:94523722:A:AG	acceptor_gain	1.0000
4:94523723:G:GG	acceptor_gain	1.0000
4:94523872:AAAGG:A	donor_loss	1.0000
4:94523873:AAGGT:A	donor_loss	1.0000
4:94523874:AGG:A	donor_loss	1.0000
4:94523875:GGTA:G	donor_loss	1.0000
4:94523876:GTA:G	donor_loss	1.0000
4:94523877:T:A	donor_loss	1.0000
4:94585557:A:AG	acceptor_gain	1.0000
4:94585558:A:AG	acceptor_gain	1.0000
4:94585559:C:G	acceptor_gain	1.0000
4:94585563:A:AG	acceptor_gain	1.0000
4:94585563:A:G	acceptor_loss	1.0000

AlphaMissense

3868 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:94455328:T:A	W14R	1.000
4:94455328:T:C	W14R	1.000
4:94455335:T:C	F16S	1.000
4:94523823:G:C	A66P	1.000
4:94640425:T:A	C420S	1.000
4:94640425:T:C	C420R	1.000
4:94640426:G:C	C420S	1.000
4:94640427:C:G	C420W	1.000
4:94654507:T:C	F444S	1.000
4:94654512:T:C	C446R	1.000
4:94654514:C:G	C446W	1.000
4:94657475:T:C	C505R	1.000
4:94657477:T:G	C505W	1.000
4:94662448:T:A	C538S	1.000
4:94662448:T:C	C538R	1.000
4:94662449:G:A	C538Y	1.000
4:94662449:G:C	C538S	1.000
4:94662450:C:G	C538W	1.000
4:94662457:T:A	C541S	1.000
4:94662458:G:A	C541Y	1.000
4:94662458:G:C	C541S	1.000
4:94662523:T:C	C563R	1.000
4:94662524:G:A	C563Y	1.000
4:94662525:C:G	C563W	1.000
4:94662532:T:C	C566R	1.000
4:94662533:G:A	C566Y	1.000
4:94662534:C:G	C566W	1.000
4:94664033:T:C	L586P	1.000
4:94664035:T:C	C587R	1.000
4:94664037:T:G	C587W	1.000

dbSNP variants (sampled 300 via entrez): RS10000208 (4:94545944 A>G), RS1000021794 (4:94633949 G>C), RS1000024591 (4:94473592 T>C), RS1000028354 (4:94569667 G>A), RS1000035588 (4:94588329 C>T), RS1000052795 (4:94633680 G>A), RS1000069673 (4:94547539 C>T), RS1000074216 (4:94620390 C>G), RS1000082598 (4:94510411 C>T), RS1000126702 (4:94480324 A>G), RS1000129278 (4:94490578 C>T), RS10001372 (4:94609104 T>A,C), RS1000148654 (4:94535426 G>A), RS1000196383 (4:94578340 A>C), RS1000216918 (4:94500453 A>G)

Disease associations

OMIM: gene MIM:605904 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000488_14	Prostate cancer	1.000000e-11
GCST000488_8	Prostate cancer	4.000000e-15
GCST001525_27	Visceral fat	9.000000e-06
GCST002591_11	Lewy body disease	8.000000e-06
GCST002642_4	Response to simvastatin treatment (PCSK9 protein level change)	5.000000e-06
GCST003501_6	Asparaginase-induced acute pancreatitis in acute lymphoblastic leukemia (onset time)	3.000000e-07
GCST004599_90	Mean platelet volume	3.000000e-09
GCST005196_120	Coronary artery disease	1.000000e-07
GCST006630_62	Diastolic blood pressure	4.000000e-10
GCST007269_38	Pulse pressure	1.000000e-11
GCST008161_121	Waist circumference adjusted for body mass index	9.000000e-06
GCST009158_10	Uterine fibroids	5.000000e-08
GCST010320_80	PR interval	6.000000e-09
GCST010321_212	PR interval	9.000000e-09
GCST010796_4418	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST011365_10	Myocardial infarction	6.000000e-09
GCST90002395_578	Mean platelet volume	3.000000e-16

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006799	Lewy body dementia measurement
EFO:0006899	PCSK9 protein measurement
EFO:1001507	asparaginase-induced acute pancreatitis
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004462	PR interval
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067139 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2433320	PDLIM5	3	2.00	1	fluoxetine
rs2433322	PDLIM5		0.00	0
rs2452600	PDLIM5		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.69	Kd	2.031	nM	CHEMBL5653589
8.68	ED50	2.09	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148968: Binding affinity to human PDLIM5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0020	uM

CTD chemical–gene interactions

91 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	4
trichostatin A	affects cotreatment, decreases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
Acetaminophen	affects expression, decreases expression	2
Tretinoin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652010	Binding	Binding affinity to human PDLIM5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.