PALM3

Summary

PALM3 (paralemmin 3, HGNC:33274) is a protein-coding gene on chromosome 19p13.12, encoding Paralemmin-3 (A6NDB9). ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling.

Predicted to enable ATP binding activity. Involved in Toll signaling pathway; negative regulation of cytokine-mediated signaling pathway; and response to lipopolysaccharide. Predicted to be located in cytoplasm and plasma membrane.

Source: NCBI Gene 342979 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 119 total
• MANE Select transcript: NM_001145028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33274
Approved symbol	PALM3
Name	paralemmin 3
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187867
Ensembl biotype	protein_coding
OMIM	621051
Entrez	342979

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000589048, ENST00000661591, ENST00000669674

RefSeq mRNA: 2 — MANE Select: NM_001145028 NM_001145028, NM_001367327

CCDS: CCDS46001, CCDS92540

Canonical transcript exons

ENST00000669674 — 7 exons

Exon	Start	End
ENSE00001762073	14057351	14057431
ENSE00002950433	14053367	14055226
ENSE00003604400	14055380	14055425
ENSE00003619830	14056429	14056513
ENSE00003674654	14056662	14056804
ENSE00003856932	14059115	14059163
ENSE00003880158	14061940	14062076

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 93.38.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1861 / max 79.8898, expressed in 440 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179591	0.4980	247
179594	0.4307	140
179592	0.1337	75
179593	0.0717	39
179596	0.0214	12
179597	0.0195	10
179595	0.0111	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	93.38	gold quality
right lobe of liver	UBERON:0001114	91.33	gold quality
liver	UBERON:0002107	88.30	gold quality
adult mammalian kidney	UBERON:0000082	87.77	gold quality
body of pancreas	UBERON:0001150	84.61	gold quality
kidney	UBERON:0002113	83.87	gold quality
body of stomach	UBERON:0001161	82.37	gold quality
cortex of kidney	UBERON:0001225	81.89	gold quality
right lobe of thyroid gland	UBERON:0001119	81.74	gold quality
pancreas	UBERON:0001264	80.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.66	gold quality
stomach	UBERON:0000945	79.06	gold quality
testis	UBERON:0000473	78.58	gold quality
left testis	UBERON:0004533	78.44	gold quality
left lobe of thyroid gland	UBERON:0001120	78.41	gold quality
right testis	UBERON:0004534	78.28	gold quality
thyroid gland	UBERON:0002046	77.73	gold quality
fundus of stomach	UBERON:0001160	77.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.62	gold quality
cortical plate	UBERON:0005343	73.33	gold quality
islet of Langerhans	UBERON:0000006	72.20	gold quality
ganglionic eminence	UBERON:0004023	71.63	gold quality
hypothalamus	UBERON:0001898	71.03	gold quality
right lung	UBERON:0002167	69.89	gold quality
right uterine tube	UBERON:0001302	68.51	gold quality
duodenum	UBERON:0002114	67.90	gold quality
anterior cingulate cortex	UBERON:0009835	67.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.50	gold quality
upper lobe of left lung	UBERON:0008952	66.49	gold quality
ventricular zone	UBERON:0003053	66.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting PALM3, 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-4692	100.00	67.32	2066
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
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-MIR-548AN	99.97	70.91	2817
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-661	99.09	65.94	2062

Literature-anchored findings (GeneRIF, showing 1)

• These results suggest that PALM3 may function as an adaptor in the LPS- Toll-like receptor 4 signaling and the interaction of SIGIRR with PALM3 may partly account for the mechanism of the negatively regulatory effect of SIGIRR. (PMID:21187075)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	palm3	ENSDARG00000071215
mus_musculus	Palm3	ENSMUSG00000047986
rattus_norvegicus	Palm3	ENSRNOG00000005729

Paralogs (3): PALMD (ENSG00000099260), PALM (ENSG00000099864), PALM2AKAP2 (ENSG00000157654)

Protein

Protein identifiers

Paralemmin-3 — A6NDB9 (reviewed: A6NDB9)

All UniProt accessions (3): A0A590UJ23, A0A590UJ36, K7EKN5

UniProt curated annotations — full annotation on UniProt →

Function. ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling.

Subunit / interactions. Interacts with SIGIRR.

Subcellular location. Cytoplasm. Cell membrane.

Post-translational modifications. Palmitoylated on Cys-667 and Cys-669 and prenylated on Cys-670; which is required for membrane association.

Induction. Up-regulated by bacterial lipopolysaccharides (LPS).

Similarity. Belongs to the paralemmin family.

RefSeq proteins (2): NP_001138500, NP_001354256 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004965	Paralemmin	Family
IPR024149	Paralemmin-3	Family

Pfam: PF03285

UniProt features (29 total): modified residue 13, compositionally biased region 4, region of interest 4, lipid moiety-binding region 3, coiled-coil region 2, chain 1, propeptide 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NDB9-F1	51.53	0.12

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): 124, 143, 151, 155, 157, 260, 301, 325, 375, 420, 544, 660, 670, 667, 669, 670

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 51 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_CYTOKINE_STIMULUS, APPIERTO_RESPONSE_TO_FENRETINIDE_UP, GOBP_REGULATION_OF_RESPONSE_TO_CYTOKINE_STIMULUS, GOBP_RESPONSE_TO_MOLECULE_OF_BACTERIAL_ORIGIN, GOBP_REGULATION_OF_CELL_SHAPE, chr19p13, GOBP_RESPONSE_TO_BACTERIUM, GOMF_ADENYL_NUCLEOTIDE_BINDING, MEISSNER_ES_ICP_WITH_H3K4ME3, MEISSNER_NPC_ICP_WITH_H3_UNMETHYLATED

GO Biological Process (4): negative regulation of cytokine-mediated signaling pathway (GO:0001960), Toll signaling pathway (GO:0008063), regulation of cell shape (GO:0008360), response to lipopolysaccharide (GO:0032496)

GO Molecular Function (1): ATP binding (GO:0005524)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of cytokine-mediated signaling pathway	1
negative regulation of signal transduction	1
cytokine-mediated signaling pathway	1
negative regulation of response to cytokine stimulus	1
cell surface receptor signaling pathway	1
regulation of cell morphogenesis	1
regulation of biological quality	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PALM3	SIGIRR	Q6IA17	553
PALM3	C19orf67	A6NJJ6	476
PALM3	TSSC4	Q9Y5U2	462
PALM3	THSD4	Q6ZMP0	443
PALM3	POU6F2	P78424	438
PALM3	COBL	O75128	430
PALM3	IFIT1B	Q5T764	425
PALM3	FPGS	Q05932	423
PALM3	ADAMTS12	P58397	419
PALM3	OR2W3	Q7Z3T1	413
PALM3	SIM2	Q14190	410
PALM3	CTSE	P14091	405
PALM3	CSMD3	Q7Z407	404
PALM3	SLC6A2	P23975	391
PALM3	GRIA1	P42261	387
PALM3	KIZ	Q2M2Z5	387

IntAct

23 interactions, top by confidence:

A	B	Type	Score
S1PR2	PALM3	psi-mi:“MI:0914”(association)	0.530
CD69	PALM3	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
SIGIRR	PALM3	psi-mi:“MI:0915”(physical association)	0.510
PALM3	USP11	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	PALM3	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	VWA8	psi-mi:“MI:0914”(association)	0.350
POLR2B	PALM3	psi-mi:“MI:0914”(association)	0.350
MAGEA3	PALM3	psi-mi:“MI:0914”(association)	0.350
MYH4	PALM3	psi-mi:“MI:0914”(association)	0.350
RABGGTA	PALM3	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
GABARAPL2	PALM3	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (17): PALM3 (Two-hybrid), PALM3 (Proximity Label-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Protein-RNA), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), PALM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA9, A2TJV2, A4FU49, A6NDB9, A6X8Z5, D3ZAQ5, P0C671, P10636, P10637, P48681, P58871, Q14676, Q2YDF7, Q3MI48, Q4R729, Q5EBJ4, Q5PSV9, Q5S6V2, Q5SWP3, Q5TM66, Q5TM68, Q5U2M8, Q5YCV9, Q5YCW0, Q5YCW1, Q640N3, Q68A65, Q68DA7, Q6NYC8, Q6ZW13, Q767L8, Q7YR40, Q7Z6I6, Q811Q2, Q8BHB9, Q8BHW6, Q8BQ30, Q8CB87, Q8CC96, Q8IXJ9

Diamond homologs: A2TJV2, A6NDB9, O54931, Q2MJV9, Q3MHH7, Q4KM62, Q7ZX27, Q9JHU2, Q9NP74, Q9Y2D5, Q9YGL6, O75781, Q2MJV8, Q5U301, Q920Q0, Q9Z0P4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

682 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14055374:ACTT:A	donor_loss	1.0000
19:14055376:TTA:T	donor_loss	1.0000
19:14055377:TAC:T	donor_loss	1.0000
19:14055378:A:C	donor_loss	1.0000
19:14055379:C:CA	donor_loss	1.0000
19:14055423:ACCC:A	acceptor_loss	1.0000
19:14055424:CC:C	acceptor_gain	1.0000
19:14055425:CC:C	acceptor_gain	1.0000
19:14055425:CCTG:C	acceptor_loss	1.0000
19:14055426:CTGC:C	acceptor_loss	1.0000
19:14055427:T:A	acceptor_loss	1.0000
19:14056660:A:AC	donor_gain	1.0000
19:14056661:C:CA	donor_gain	1.0000
19:14056805:C:CC	acceptor_gain	1.0000
19:14056811:A:T	acceptor_gain	1.0000
19:14059113:A:AC	donor_gain	1.0000
19:14059114:C:CC	donor_gain	1.0000
19:14059114:CA:C	donor_gain	1.0000
19:14059114:CAG:C	donor_gain	1.0000
19:14055242:G:C	acceptor_gain	0.9900
19:14055242:G:GC	acceptor_gain	0.9900
19:14055378:A:AC	donor_gain	0.9900
19:14055379:C:CC	donor_gain	0.9900
19:14055379:CCTA:C	donor_gain	0.9900
19:14055426:C:CC	acceptor_gain	0.9900
19:14056423:CCTCA:C	donor_loss	0.9900
19:14056424:CTCA:C	donor_loss	0.9900
19:14056425:TCAC:T	donor_loss	0.9900
19:14056426:CA:C	donor_loss	0.9900
19:14056427:A:AG	donor_loss	0.9900

AlphaMissense

4405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14056781:C:A	W50C	0.994
19:14056781:C:G	W50C	0.994
19:14056783:A:G	W50R	0.993
19:14056783:A:T	W50R	0.993
19:14059117:C:G	A15P	0.993
19:14056499:A:G	L95P	0.989
19:14059119:A:T	I14N	0.987
19:14057424:C:G	R18P	0.985
19:14056506:A:G	S93P	0.982
19:14057351:C:A	K42N	0.982
19:14057351:C:G	K42N	0.982
19:14057406:A:G	I24T	0.982
19:14057418:A:G	L20P	0.981
19:14059116:G:T	A15D	0.980
19:14056779:A:G	L51P	0.979
19:14056799:C:A	K44N	0.979
19:14056799:C:G	K44N	0.979
19:14056791:C:G	R47P	0.978
19:14056490:A:G	L98S	0.977
19:14056689:A:G	I81T	0.976
19:14057426:C:A	K17N	0.976
19:14057426:C:G	K17N	0.976
19:14059131:C:G	R10P	0.975
19:14056802:C:A	R43S	0.974
19:14056802:C:G	R43S	0.974
19:14059119:A:C	I14S	0.974
19:14059128:A:G	L11P	0.974
19:14054604:G:C	F341L	0.973
19:14054604:G:T	F341L	0.973
19:14054606:A:G	F341L	0.973

dbSNP variants (sampled 300 via entrez): RS1000103341 (19:14063364 C>T), RS1000361288 (19:14057952 A>G), RS1000385823 (19:14056631 G>A), RS1000949044 (19:14053090 A>G), RS1001112963 (19:14063979 C>T), RS1001256655 (19:14058855 A>G), RS1001651772 (19:14063969 A>T), RS1001729925 (19:14062280 G>C), RS1001858921 (19:14058380 A>T), RS1002018196 (19:14058470 A>G), RS1002131021 (19:14058033 G>C,T), RS1002605127 (19:14063823 C>A,T), RS1002797197 (19:14054919 C>T), RS1002997211 (19:14061218 C>T), RS1003713741 (19:14056576 G>C,T)

Disease associations

OMIM: gene MIM:621051 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90013407_163	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	6
Benzo(a)pyrene	decreases expression, decreases methylation, increases mutagenesis, affects methylation	3
entinostat	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
FR900359	increases phosphorylation	1
methyleugenol	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression, affects cotreatment	1
ferrous chloride	increases expression	1
pentanal	increases expression	1
dinophysistoxin 1	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Rotenone	increases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Zearalenone	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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