PALD1

Summary

PALD1 (phosphatase domain containing paladin 1, HGNC:23530) is a protein-coding gene on chromosome 10q22.1, encoding Paladin (Q9ULE6).

Predicted to enable protein tyrosine phosphatase activity. Located in cytosol and intracellular membrane-bounded organelle.

Source: NCBI Gene 27143 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 188 total
• MANE Select transcript: NM_014431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23530
Approved symbol	PALD1
Name	phosphatase domain containing paladin 1
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000107719
Ensembl biotype	protein_coding
OMIM	614656
Entrez	27143

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 25 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000263563, ENST00000697546, ENST00000697547, ENST00000697548, ENST00000697549, ENST00000697550, ENST00000697570, ENST00000697571, ENST00000697572, ENST00000697573, ENST00000697574, ENST00000697575, ENST00000697577, ENST00000697578, ENST00000893832, ENST00000893833, ENST00000893834, ENST00000893835, ENST00000893836, ENST00000893837, ENST00000915437, ENST00000915438, ENST00000915439, ENST00000915440, ENST00000915441, ENST00000915442, ENST00000915443, ENST00000915444, ENST00000915445, ENST00000915446, ENST00000945160, ENST00000945161, ENST00000945162

RefSeq mRNA: 1 — MANE Select: NM_014431 NM_014431

CCDS: CCDS31215

Canonical transcript exons

ENST00000263563 — 20 exons

Exon	Start	End
ENSE00000707976	70534739	70534843
ENSE00000707984	70533922	70534073
ENSE00000707987	70532995	70533070
ENSE00000707990	70532621	70532781
ENSE00000834321	70529889	70530068
ENSE00000834324	70537811	70537906
ENSE00000834325	70538280	70538408
ENSE00000834326	70538892	70539008
ENSE00000834329	70541102	70541242
ENSE00000834330	70541463	70541534
ENSE00000834331	70564364	70564519
ENSE00000933733	70547306	70547446
ENSE00000986987	70531290	70531454
ENSE00000986988	70539092	70539247
ENSE00000986989	70539580	70539762
ENSE00001186034	70529229	70529331
ENSE00001186038	70525923	70526136
ENSE00001259918	70534425	70534524
ENSE00001259952	70566581	70568450
ENSE00001628051	70478767	70479059

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 90.74.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2775 / max 220.6788, expressed in 836 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105388	2.7645	727
105390	0.8814	465
105391	0.4357	220
105389	0.1959	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	90.74	gold quality
medial globus pallidus	UBERON:0002477	87.05	gold quality
right lung	UBERON:0002167	85.35	gold quality
upper lobe of left lung	UBERON:0008952	85.31	gold quality
upper lobe of lung	UBERON:0008948	84.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.73	gold quality
globus pallidus	UBERON:0001875	83.03	gold quality
buccal mucosa cell	CL:0002336	82.58	silver quality
spinal cord	UBERON:0002240	82.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.15	gold quality
spleen	UBERON:0002106	80.74	gold quality
substantia nigra	UBERON:0002038	80.53	gold quality
lung	UBERON:0002048	80.45	gold quality
right coronary artery	UBERON:0001625	80.26	gold quality
apex of heart	UBERON:0002098	80.00	gold quality
visceral pleura	UBERON:0002401	79.73	gold quality
mucosa of stomach	UBERON:0001199	79.66	gold quality
midbrain	UBERON:0001891	79.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.45	gold quality
ventricular zone	UBERON:0003053	79.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.26	gold quality
hypothalamus	UBERON:0001898	79.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.96	gold quality
nucleus accumbens	UBERON:0001882	78.95	gold quality
amygdala	UBERON:0001876	78.44	gold quality
cerebellar hemisphere	UBERON:0002245	78.17	gold quality
tendon	UBERON:0000043	78.10	gold quality
cerebellar cortex	UBERON:0002129	78.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.90	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, KDM5B

miRNA regulators (miRDB)

104 targeting PALD1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-544A	99.84	68.66	1965

Literature-anchored findings (GeneRIF, showing 2)

• PALD (KIAA1274, paladin) has a role in inhibition of insulin’s ability to down regulate a FOXO1A-driven reporter gene, reduce upstream insulin-stimulated AKT phosphorylation, and decrease insulin receptor (IR) abundance (PMID:19727444)
• Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer’s disease. (PMID:37149695)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pald1b	ENSDARG00000039352
danio_rerio	pald1a	ENSDARG00000098946
mus_musculus	Pald1	ENSMUSG00000020092
rattus_norvegicus	Pald1	ENSRNOG00000000561

Paralogs (8): CDC14A (ENSG00000079335), CDC14B (ENSG00000081377), CDKN3 (ENSG00000100526), PTP4A1 (ENSG00000112245), PTPDC1 (ENSG00000158079), PTP4A2 (ENSG00000184007), PTP4A3 (ENSG00000184489), CDC14C (ENSG00000218305)

Protein

Protein identifiers

Paladin — Q9ULE6 (reviewed: Q9ULE6)

All UniProt accessions (7): Q9ULE6, A0A8V8TL18, A0A8V8TL27, A0A8V8TL39, A0A8V8TL47, A0A8V8TLG1, A0A8V8TMP9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in endothelial cells, and in certain larger vessels, in mural cells. In the brain, possibly expressed in microglia. Expressed in peripheral blood mononuclear cells (at protein level).

Similarity. Belongs to the paladin family.

RefSeq proteins (1): NP_055246* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003595	Tyr_Pase_cat	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR050561	PTP	Family

Pfam: PF14566

UniProt features (9 total): sequence variant 3, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULE6-F1	84.20	0.60

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 (2): 86, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): GGGACCA_MIR133A_MIR133B, HORIUCHI_WTAP_TARGETS_DN, GOLDRATH_IMMUNE_MEMORY, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_ELK3_ONLY_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GRYDER_PAX3FOXO1_TOP_ENHANCERS, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, GOMF_PROTEIN_TYROSINE_PHOSPHATASE_ACTIVITY, GRYDER_PAX3FOXO1_ENHANCERS_KO_DOWN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_PHOSPHOPROTEIN_PHOSPHATASE_ACTIVITY, GOMF_PHOSPHATASE_ACTIVITY, MTOR_UP.V1_DN

GO Biological Process (0):

GO Molecular Function (2): protein tyrosine phosphatase activity (GO:0004725), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
phosphoprotein phosphatase activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PALD1	PALLD	Q8WX93	507
PALD1	TLR9	Q9NR96	488
PALD1	LASP1	Q14847	483
PALD1	ADAMTS14	Q8WXS8	482
PALD1	ZNF646	O15015	481
PALD1	IRF7	Q92985	480
PALD1	CHST8	Q9H2A9	441
PALD1	CDH5	P33151	408
PALD1	CD93	Q9NPY3	398
PALD1	POLR2F	P41584	397
PALD1	ROBO4	Q8WZ75	394
PALD1	UPP1	Q16831	379
PALD1	FCN3	O75636	377
PALD1	KDR	P35968	373
PALD1	PECAM1	P16284	367

IntAct

51 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
NXPH3	TUBA4A	psi-mi:“MI:0914”(association)	0.530
PALD1	UNC119B	psi-mi:“MI:0914”(association)	0.530
ANGPTL7	TCP1	psi-mi:“MI:0914”(association)	0.530
UNC119	PDE8A	psi-mi:“MI:0914”(association)	0.530
IRF7	AIP	psi-mi:“MI:0914”(association)	0.500
Zbp1	PALD1	psi-mi:“MI:0915”(physical association)	0.500
PALD1	IRF7	psi-mi:“MI:0915”(physical association)	0.500
PALD1	H3C13	psi-mi:“MI:0915”(physical association)	0.400
PALD1	H1-2	psi-mi:“MI:0915”(physical association)	0.400
PALD1	LMNA	psi-mi:“MI:0915”(physical association)	0.400
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
CDK13	CCNK	psi-mi:“MI:0914”(association)	0.350
LGALS7		psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
GADD45A	CBX4	psi-mi:“MI:0914”(association)	0.350
TACR3	TCAF2	psi-mi:“MI:0914”(association)	0.350
NPAS2	FHL2	psi-mi:“MI:0914”(association)	0.350
INF2	PIPSL	psi-mi:“MI:0914”(association)	0.350

BioGRID (111): PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Proximity Label-MS), PALD1 (Proximity Label-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Affinity Capture-MS), PALD1 (Proximity Label-MS), PALD1 (Proximity Label-MS)

ESM2 similar proteins: A0A8I3NGV2, A2VE47, D3Z2R5, F1N2K1, O95479, P56201, P58499, Q08DJ7, Q09200, Q0VCN6, Q10468, Q1JPD2, Q2TBP8, Q32KV6, Q3SZL5, Q3U2U7, Q5R5N9, Q5VSG8, Q5XI31, Q5XIA1, Q5ZJH2, Q642A7, Q6MG55, Q6NZ07, Q6P1J0, Q6P6S4, Q6PBN5, Q6PD26, Q7TMC8, Q7Z3D6, Q86S40, Q8BXQ2, Q8CFX1, Q8JHZ8, Q8N0W3, Q8NHY0, Q8QZW3, Q8R553, Q8VCM8, Q8VDL4

Diamond homologs: P70261, Q6DIR8, Q6NT99, Q803E0, Q8JHZ8, Q9BVJ7, Q9ULE6, A1L1R5, A2A3K4, A7E379, O55236, O60729, O60942, P81299, Q17607, Q4JDL3, Q4QEZ7, Q5B323, Q6NY98, Q6NZK8, Q6PFY9, Q9ZQP1, Q79LY0, A4D256

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	147
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4613 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70526137:G:GG	donor_gain	1.0000
10:70529225:CCAG:C	acceptor_loss	1.0000
10:70529226:CA:C	acceptor_loss	1.0000
10:70529227:A:AG	acceptor_gain	1.0000
10:70529227:A:T	acceptor_loss	1.0000
10:70529228:G:GT	acceptor_gain	1.0000
10:70529228:GGT:G	acceptor_gain	1.0000
10:70529228:GGTAC:G	acceptor_gain	1.0000
10:70529328:GCAA:G	donor_gain	1.0000
10:70529332:G:GG	donor_gain	1.0000
10:70529883:TGCCA:T	acceptor_loss	1.0000
10:70529884:GCCAG:G	acceptor_loss	1.0000
10:70529885:CCAG:C	acceptor_loss	1.0000
10:70529886:CAG:C	acceptor_loss	1.0000
10:70529887:A:AG	acceptor_gain	1.0000
10:70529887:A:T	acceptor_loss	1.0000
10:70529887:AG:A	acceptor_gain	1.0000
10:70529888:G:GG	acceptor_gain	1.0000
10:70529888:GG:G	acceptor_gain	1.0000
10:70529888:GGGCC:G	acceptor_gain	1.0000
10:70530065:TAGG:T	donor_gain	1.0000
10:70530067:GG:G	donor_gain	1.0000
10:70530068:GG:G	donor_gain	1.0000
10:70530068:GGTA:G	donor_loss	1.0000
10:70530069:GTAA:G	donor_loss	1.0000
10:70530070:T:A	donor_loss	1.0000
10:70531276:C:CA	acceptor_gain	1.0000
10:70531277:G:A	acceptor_gain	1.0000
10:70531289:GGA:G	acceptor_gain	1.0000
10:70531289:GGAGT:G	acceptor_gain	1.0000

AlphaMissense

5608 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:70526127:T:A	V59D	0.997
10:70526133:T:C	I61T	0.995
10:70526133:T:G	I61S	0.994
10:70529248:T:C	F69L	0.994
10:70529250:C:A	F69L	0.994
10:70529250:C:G	F69L	0.994
10:70526133:T:A	I61N	0.993
10:70541529:T:C	F706L	0.992
10:70541531:T:A	F706L	0.992
10:70541531:T:G	F706L	0.992
10:70547353:G:C	K723N	0.992
10:70547353:G:T	K723N	0.992
10:70541530:T:C	F706S	0.990
10:70538959:G:C	R507P	0.987
10:70547421:A:T	E746V	0.987
10:70541496:A:C	S695R	0.985
10:70541498:T:A	S695R	0.985
10:70541498:T:G	S695R	0.985
10:70541523:G:C	G704R	0.984
10:70526121:C:A	A57D	0.983
10:70547373:T:C	L730P	0.983
10:70547382:T:A	V733D	0.983
10:70538956:T:C	F506S	0.982
10:70564431:G:C	R777P	0.982
10:70529249:T:C	F69S	0.981
10:70538955:T:C	F506L	0.981
10:70538957:C:A	F506L	0.981
10:70538957:C:G	F506L	0.981
10:70547384:A:C	S734R	0.981
10:70547386:C:A	S734R	0.981

dbSNP variants (sampled 300 via entrez): RS1000046601 (10:70500802 G>A), RS1000047686 (10:70538672 C>G,T), RS1000064922 (10:70478406 C>G,T), RS1000134036 (10:70549605 A>G), RS1000144507 (10:70463060 T>C,G), RS1000232230 (10:70483588 C>T), RS1000232463 (10:70478351 C>G,T), RS1000275394 (10:70532352 A>G), RS1000301198 (10:70521654 C>T), RS1000311736 (10:70568766 G>A), RS1000313749 (10:70568663 G>C), RS1000328567 (10:70558791 G>A,C), RS1000329565 (10:70521432 G>A), RS1000397440 (10:70514694 G>A), RS1000425568 (10:70489106 T>C)

Disease associations

OMIM: gene MIM:614656 | disease phenotypes: MIM:603553

GenCC curated gene-disease

Mondo (2): familial hemophagocytic lymphohistiocytosis 2 (MONDO:0011337), autoinflammatory syndrome (MONDO:0019751)

Orphanet (2): Familial hemophagocytic lymphohistiocytosis (Orphanet:540), Autoinflammatory syndrome (Orphanet:93665)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004632_71	Lymphocyte percentage of white cells	1.000000e-09
GCST006484_11	Type 2 diabetes	1.000000e-06
GCST009219_5	Superior frontal gyrus volume	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537250	Hemophagocytic lymphohistiocytosis, familial, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
Estradiol	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
cupric oxide	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Am 580	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Rosiglitazone	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION