PTX4

Summary

PTX4 (pentraxin 4, HGNC:14171) is a protein-coding gene on chromosome 16p13.3, encoding Pentraxin-4 (Q96A99).

This gene belongs to the pentraxin superfamily, whose members encode highly conserved multifunctional proteins. The encoded protein, like other members of this family, contains a conserved pentraxin domain at the C-terminus. The highest levels of expression of the protein were observed in bone marrow, small intestine and testes.

Source: NCBI Gene 390667 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 124 total — 1 pathogenic
• MANE Select transcript: NM_001328608

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14171
Approved symbol	PTX4
Name	pentraxin 4
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000251692
Ensembl biotype	protein_coding
OMIM	613442
Entrez	390667

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000293922, ENST00000440447, ENST00000447419

RefSeq mRNA: 2 — MANE Select: NM_001328608 NM_001013658, NM_001328608

CCDS: CCDS32362, CCDS86492

Canonical transcript exons

ENST00000447419 — 3 exons

Exon	Start	End
ENSE00001692996	1488769	1488944
ENSE00002249064	1487316	1487970
ENSE00003532426	1485886	1486579

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 81.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0228 / max 9.0022, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155851	0.0228	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.99	gold quality
leukocyte	CL:0000738	58.94	gold quality
monocyte	CL:0000576	58.89	gold quality
granulocyte	CL:0000094	57.55	gold quality
bone marrow cell	CL:0002092	52.62	gold quality
bone marrow	UBERON:0002371	52.25	gold quality
right adrenal gland cortex	UBERON:0035827	49.87	gold quality
stromal cell of endometrium	CL:0002255	49.49	gold quality
left adrenal gland cortex	UBERON:0035825	48.35	gold quality
right adrenal gland	UBERON:0001233	47.94	gold quality
left adrenal gland	UBERON:0001234	46.80	gold quality
adrenal gland	UBERON:0002369	45.24	gold quality
apex of heart	UBERON:0002098	44.38	silver quality
right coronary artery	UBERON:0001625	43.18	silver quality
blood	UBERON:0000178	43.04	gold quality
skeletal muscle tissue	UBERON:0001134	43.01	gold quality
smooth muscle tissue	UBERON:0001135	42.41	gold quality
muscle tissue	UBERON:0002385	42.39	silver quality
lower esophagus muscularis layer	UBERON:0035833	42.03	gold quality
colonic epithelium	UBERON:0000397	42.01	gold quality
gastrocnemius	UBERON:0001388	42.00	silver quality
lower esophagus	UBERON:0013473	41.94	gold quality
muscle of leg	UBERON:0001383	41.08	silver quality
endometrium	UBERON:0001295	41.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	40.44	gold quality
right testis	UBERON:0004534	40.25	gold quality
urinary bladder	UBERON:0001255	40.07	silver quality
heart left ventricle	UBERON:0002084	40.06	gold quality
descending thoracic aorta	UBERON:0002345	39.95	gold quality
prefrontal cortex	UBERON:0000451	39.76	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Study of long pentraxin PTX4 in silico and by transcript expression shows that the gene clusters alone in phylogenetic analysis, is well conserved from mammals to lower vertebrates, and has a unique pattern of messenger RNA expression. (PMID:20357257)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zmp:0000000984	ENSDARG00000090107
danio_rerio		ENSDARG00000112052
mus_musculus	Ptx4	ENSMUSG00000044172
rattus_norvegicus	Ptx4	ENSRNOG00000060934

Paralogs (5): NPTX2 (ENSG00000106236), CRP (ENSG00000132693), APCS (ENSG00000132703), PTX3 (ENSG00000163661), NPTX1 (ENSG00000171246)

Protein

Protein identifiers

Pentraxin-4 — Q96A99 (reviewed: Q96A99)

All UniProt accessions (2): H3BSQ8, Q96A99

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Widely expressed at low levels with highest levels in small intestine, testis and brain. Very low expression in endothelial cells, monocytes, neutrophils and lymphocytes. Isoform 1 is not expressed in small intestine.

Cofactor. Binds 2 calcium ions per subunit.

Induction. Not induced by bacterial lipopolysaccharideS (LPS) or IL1/interleukin-1 in endothelium, monocytes or neutrophils. Not induced by PHA in lymphocytes.

Miscellaneous. Not expressed in small intestine.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96A99-1	2, PTX4(2)	yes
Q96A99-2	1, PTX4(1), Long

RefSeq proteins (2): NP_001013680, NP_001315537* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001759	PTX_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR051360	Neuronal_Pentraxin_Related	Family

Pfam: PF00354

UniProt features (23 total): binding site 7, sequence variant 7, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A99-F1	78.83	0.57

Functional residue map

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

Ligand- & substrate-binding residues (7): 408; 408; 322; 323; 406; 406; 407

Disulfide bonds (1): 300–364

Glycosylation sites (2): 67, 91

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): DARWICHE_PAPILLOMA_PROGRESSION_RISK, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GSE10239_MEMORY_VS_KLRG1INT_EFF_CD8_TCELL_UP, GSE3039_ALPHAALPHA_CD8_TCELL_VS_B2_BCELL_UP, GSE5589_WT_VS_IL6_KO_LPS_AND_IL6_STIM_MACROPHAGE_45MIN_UP, GSE19888_ADENOSINE_A3R_INH_VS_ACT_IN_MAST_CELL_DN, GSE19941_UNSTIM_VS_LPS_AND_IL10_STIM_IL10_KO_MACROPHAGE_DN, GSE19941_UNSTIM_VS_LPS_AND_IL10_STIM_IL10_KO_NFKBP50_KO_MACROPHAGE_DN, IVANOVA_HEMATOPOIESIS_STEM_CELL_AND_PROGENITOR, chr16p13, GSE44649_WT_VS_MIR155_KO_ACTIVATED_CD8_TCELL_DN

GO Biological Process (0):

GO Molecular Function (1): metal ion binding (GO:0046872)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTX4	OCA2	Q04671	660
PTX4	RAB44	Q7Z6P3	485
PTX4	FCN1	O00602	417
PTX4	FOXRED2	Q8IWF2	406
PTX4	COLEC12	Q5KU26	377
PTX4	SAMD10	Q9BYL1	371
PTX4	VPS52	Q8N1B4	363
PTX4	HROB	Q8N3J3	357
PTX4	TREML2	Q5T2D2	357
PTX4	FCN2	Q15485	356
PTX4	EXOC3L1	Q86VI1	348
PTX4	EPHX3	Q9H6B9	347
PTX4	NPTX2	P47972	340
PTX4	GPATCH1	Q9BRR8	324
PTX4	CLEC4E	Q9ULY5	323

IntAct

3 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350
PTX4	NPTXR	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): LRRC1 (Affinity Capture-MS), NPTXR (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A0EQL2, D3YZF7, D7PDD4, O15533, O55237, O70394, O70540, O95866, P04278, P05111, P07994, P08689, P0C6B3, P0DP72, P15196, P17490, P18627, P40238, P55101, P60882, P97497, Q00657, Q08351, Q14393, Q14773, Q16671, Q3SWY4, Q5BK54, Q5NKT8, Q5TJE4, Q61790, Q61826, Q62588, Q6PZD2, Q6UVK1, Q6UWB1, Q7Z7M0, Q7Z7M1, Q86VR7

Diamond homologs: A0A1D5NSM8, A0JNA2, A2AVA0, A2AX52, D3YXF5, O02839, O19063, O35764, O43405, O70340, O76536, O89029, O95502, O96530, P02741, P02743, P06205, P06206, P06207, P06681, P07202, P07629, P08607, P09871, P0C6B8, P10643, P12246, P13944, P14151, P14847, P15697, P18337, P23680, P32018, P47970, P47971, P47972, P48199, P49254, P49262

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
150284	GRCh38/hg38 16p13.3-13.12(chr16:43732-13326806)x3	Pathogenic

SpliceAI

464 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1486580:C:CC	acceptor_gain	1.0000
16:1487691:T:A	donor_gain	0.9900
16:1488257:T:A	donor_gain	0.9900
16:1488258:C:A	donor_gain	0.9900
16:1486576:CAAA:C	acceptor_gain	0.9800
16:1487763:T:A	donor_gain	0.9800
16:1488278:G:A	donor_gain	0.9700
16:1487314:A:AC	donor_gain	0.9600
16:1487315:C:CC	donor_gain	0.9600
16:1487315:CT:C	donor_gain	0.9600
16:1487315:CTCT:C	donor_gain	0.9600
16:1488240:C:CT	donor_gain	0.9600
16:1487376:TGAG:T	donor_gain	0.9500
16:1487481:G:A	donor_gain	0.9500
16:1487966:CGGAA:C	acceptor_gain	0.9500
16:1488241:C:CT	donor_gain	0.9500
16:1487657:T:TA	donor_gain	0.9400
16:1486579:AC:A	acceptor_loss	0.9300
16:1486580:C:CG	acceptor_loss	0.9300
16:1487971:C:CC	acceptor_gain	0.9300
16:1488250:G:C	donor_gain	0.9300
16:1488372:C:CA	donor_gain	0.9300
16:1486578:AA:A	acceptor_gain	0.9200
16:1486588:A:T	acceptor_loss	0.9200
16:1487670:C:A	donor_gain	0.9200
16:1486577:AAA:A	acceptor_gain	0.9100
16:1488372:CCGGA:C	donor_gain	0.9100
16:1487307:GGTAC:G	donor_loss	0.9000
16:1487308:GTAC:G	donor_loss	0.9000
16:1487309:TAC:T	donor_loss	0.9000

AlphaMissense

3046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1486134:G:C	F414L	0.985
16:1486134:G:T	F414L	0.985
16:1486136:A:G	F414L	0.985
16:1486473:G:C	S301R	0.985
16:1486473:G:T	S301R	0.985
16:1486475:T:G	S301R	0.985
16:1486275:C:A	W367C	0.982
16:1486275:C:G	W367C	0.982
16:1486296:C:A	W360C	0.981
16:1486296:C:G	W360C	0.981
16:1486210:A:C	F389C	0.980
16:1486277:A:G	W367R	0.980
16:1486277:A:T	W367R	0.980
16:1486117:A:C	F420C	0.979
16:1486335:G:C	F347L	0.979
16:1486335:G:T	F347L	0.979
16:1486337:A:G	F347L	0.979
16:1486210:A:G	F389S	0.978
16:1486552:A:C	F275C	0.978
16:1486086:C:A	W430C	0.977
16:1486086:C:G	W430C	0.977
16:1486116:G:C	F420L	0.977
16:1486116:G:T	F420L	0.977
16:1486118:A:G	F420L	0.977
16:1486209:G:C	F389L	0.976
16:1486209:G:T	F389L	0.976
16:1486211:A:G	F389L	0.976
16:1486551:G:C	F275L	0.973
16:1486551:G:T	F275L	0.973
16:1486553:A:G	F275L	0.973

dbSNP variants (sampled 300 via entrez): RS1000025692 (16:1488728 A>C,G), RS1000493417 (16:1490224 C>T), RS1001133099 (16:1487722 G>A,C), RS1001821957 (16:1489669 C>T), RS1001992519 (16:1490494 G>C), RS1002279614 (16:1490253 G>A,C), RS1004378748 (16:1488241 C>T), RS1005036685 (16:1486466 G>A,C), RS1005149119 (16:1490579 A>G), RS1005181581 (16:1490822 C>T), RS1005479057 (16:1486644 C>G,T), RS1006493980 (16:1486679 C>T), RS1006525014 (16:1486911 G>A,C), RS1007727546 (16:1490570 A>G), RS1008531871 (16:1488654 C>T)

Disease associations

OMIM: gene MIM:613442 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006979_1052	Heel bone mineral density	1.000000e-12
GCST007691_26	Femoral neck bone mineral density	1.000000e-16
GCST007843_25	Rheumatoid arthritis	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0007785	femoral neck bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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