NPTXR

Summary

NPTXR (neuronal pentraxin receptor, HGNC:7954) is a protein-coding gene on chromosome 22q13.1, encoding Neuronal pentraxin receptor (O95502). May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses.

This gene encodes a protein similar to the rat neuronal pentraxin receptor. The rat pentraxin receptor is an integral membrane protein that is thought to mediate neuronal uptake of the snake venom toxin, taipoxin, and its transport into the synapses. Studies in rat indicate that translation of this mRNA initiates at a non-AUG (CUG) codon. This may also be true for mouse and human, based on strong sequence conservation amongst these species.

Source: NCBI Gene 23467 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_014293

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7954
Approved symbol	NPTXR
Name	neuronal pentraxin receptor
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000221890
Ensembl biotype	protein_coding
OMIM	609474
Entrez	23467

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000333039, ENST00000718437

RefSeq mRNA: 1 — MANE Select: NM_014293 NM_014293

CCDS: CCDS33647

Canonical transcript exons

ENST00000333039 — 5 exons

Exon	Start	End
ENSE00001302714	38823083	38823262
ENSE00001309035	38828287	38828512
ENSE00001314270	38843235	38844028
ENSE00001325182	38818452	38822833
ENSE00001326609	38826500	38826747

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4315 / max 826.5600, expressed in 1126 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194239	6.0585	1078
194237	0.9163	140
194233	0.2293	80
194235	0.1198	48
194234	0.0422	23
194238	0.0391	23
194236	0.0262	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	98.26	gold quality
frontal pole	UBERON:0002795	98.23	gold quality
CA1 field of hippocampus	UBERON:0003881	97.30	gold quality
right frontal lobe	UBERON:0002810	96.51	gold quality
prefrontal cortex	UBERON:0000451	96.46	gold quality
cingulate cortex	UBERON:0003027	96.34	gold quality
anterior cingulate cortex	UBERON:0009835	96.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.20	gold quality
Ammon’s horn	UBERON:0001954	96.14	gold quality
amygdala	UBERON:0001876	96.10	gold quality
frontal cortex	UBERON:0001870	95.69	gold quality
neocortex	UBERON:0001950	95.18	gold quality
cerebral cortex	UBERON:0000956	95.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.98	gold quality
temporal lobe	UBERON:0001871	94.95	gold quality
orbitofrontal cortex	UBERON:0004167	94.61	gold quality
entorhinal cortex	UBERON:0002728	93.91	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.96	gold quality
superior frontal gyrus	UBERON:0002661	92.70	gold quality
cerebellar cortex	UBERON:0002129	92.59	gold quality
cerebellar hemisphere	UBERON:0002245	92.57	gold quality
parietal lobe	UBERON:0001872	92.45	gold quality
postcentral gyrus	UBERON:0002581	92.14	gold quality
cerebellum	UBERON:0002037	91.94	gold quality
telencephalon	UBERON:0001893	91.44	gold quality
ganglionic eminence	UBERON:0004023	90.64	gold quality
cerebellar vermis	UBERON:0004720	90.49	gold quality
paraflocculus	UBERON:0005351	89.85	gold quality
forebrain	UBERON:0001890	89.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	57.96
E-CURD-10	no	28.74
E-ANND-3	no	2.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

165 targeting NPTXR, 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-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743

Literature-anchored findings (GeneRIF, showing 4)

• The purpose of the present study was to assess the toxic effect of taipoxin in SCLC-cell lines and to determine if toxicity correlates to NPR and NP1 and NP2 expression levels. (PMID:16115696)
• study suggests that NCAM-120, alpha-dystroglycan, and NPR are candidate biomarkers in CSF for neurodegenerative diseases, and that the changes in the CSF level of NPR may be specific for Alzheimer’s disease (PMID:19368810)
• Decreased cerebrospinal fluid neuronal pentraxin receptor is associated with PET-Abeta load and cerebrospinal fluid Abeta in a pilot study of Alzheimer’s disease. (PMID:32450185)
• non-AUG translation initiation site. Comparison of rat determined N-terminal amino acid sequence with cDNA sequence indicates that a CUG codon is used as an initiator codon and codes for a methionine. The CTG is present in cDNAs of mouse, rat, and human. (PMID:9261167)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbx6a	ENSDARG00000071051
danio_rerio	cbx6b	ENSDARG00000097543
mus_musculus	Nptxr	ENSMUSG00000022421
rattus_norvegicus	Nptxr	ENSRNOG00000016156
caenorhabditis_elegans		WBGENE00001995
caenorhabditis_elegans		WBGENE00007615

Paralogs (8): CBX5 (ENSG00000094916), CBX7 (ENSG00000100307), CBX1 (ENSG00000108468), CBX3 (ENSG00000122565), CBX8 (ENSG00000141570), CBX4 (ENSG00000141582), CBX2 (ENSG00000173894), CBX6 (ENSG00000183741)

Protein

Protein identifiers

Neuronal pentraxin receptor — O95502 (reviewed: O95502)

All UniProt accessions (2): A0A1X7SBT7, O95502

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses.

Subunit / interactions. Heteropentamer with NPTX1 and/or NPTX2. Also binds taipoxin-associated calcium-binding protein 49 (TCBP49/RCN2). Interacts with KLHL2.

Subcellular location. Membrane.

Post-translational modifications. Ubiquitinated by a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing KLHL2.

Cofactor. Binds 2 calcium ions per subunit.

RefSeq proteins (1): NP_055108* (*=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 (19 total): binding site 7, glycosylation site 3, topological domain 2, region of interest 2, chain 1, disulfide bond 1, transmembrane region 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95502-F1	77.69	0.45

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): 425; 426; 427; 427; 437; 347; 425

Disulfide bonds (1): 322–383

Glycosylation sites (3): 42, 216, 463

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): LFA1_Q6, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, BROWNE_HCMV_INFECTION_24HR_UP, CHEN_HOXA5_TARGETS_6HR_DN, AACTTT_UNKNOWN, MODULE_447, CTAWWWATA_RSRFC4_Q2, GOCC_SYNAPSE, chr22q13

GO Biological Process (0):

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

GO Cellular Component (2): membrane (GO:0016020), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	1
cellular anatomical structure	1
synapse	1

Protein interactions and networks

STRING

942 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPTXR	RCN2	Q14257	926
NPTXR	NPR1	P16066	848
NPTXR	NPR3	P17342	817
NPTXR	NPR2	P20594	799
NPTXR	NPPA	P01160	740
NPTXR	NPTX2	P47972	691
NPTXR	OCA2	Q04671	637
NPTXR	NPPC	P23582	582
NPTXR	NPTX1	Q15818	522
NPTXR	ATP2B2	Q01814	516
NPTXR	GRIA4	P48058	475
NPTXR	ATP2B4	P23634	463
NPTXR	CYB5B	O43169	456
NPTXR	CYB5A	P00167	450
NPTXR	PAQR8	Q8TEZ7	445

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PHC1	CBX4	psi-mi:“MI:0914”(association)	0.790
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CYB5D2	ABLIM1	psi-mi:“MI:0914”(association)	0.530
CYB5D2	SUN1	psi-mi:“MI:0914”(association)	0.530
	NPTXR	psi-mi:“MI:0407”(direct interaction)	0.440
AQP6	NPTXR	psi-mi:“MI:0915”(physical association)	0.400
PARD3B	PGP	psi-mi:“MI:0914”(association)	0.350
SELENON	ACTL6B	psi-mi:“MI:0914”(association)	0.350
SFTPC	MPZL1	psi-mi:“MI:0914”(association)	0.350
SIAE	NPTXR	psi-mi:“MI:0914”(association)	0.350
NPTX2	NPTXR	psi-mi:“MI:0914”(association)	0.350
NPTX1	NPTXR	psi-mi:“MI:0914”(association)	0.350
PTX4	NPTXR	psi-mi:“MI:0914”(association)	0.350
NPTXR	FN1	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
CST9L	QSOX1	psi-mi:“MI:0914”(association)	0.350
NPTXR	ACACB	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): NPTXR (Affinity Capture-MS), NPTXR (Affinity Capture-MS), NPTXR (Affinity Capture-MS), NPTXR (Affinity Capture-MS), NPTXR (Affinity Capture-MS), CORO1A (Affinity Capture-MS), NPTXR (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), NPTXR (Affinity Capture-MS), NPTXR (Affinity Capture-MS), NPTXR (Affinity Capture-MS), NPTXR (Affinity Capture-MS), FN1 (Affinity Capture-MS), HOOK2 (Affinity Capture-MS), ACACA (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0A494C0Y3, A0JNH6, A0JNN8, A1A5D9, A2ARS0, A5A769, A5PJP1, A6NC98, A7YWC8, C9JTQ0, O15049, O35764, O95502, P0C7N4, P0DPE3, P58660, Q0P5D1, Q1HCM0, Q2TAC2, Q3LUD3, Q3LUD4, Q3TMW1, Q3UMT1, Q4QRL3, Q5BLP8, Q5JTB6, Q6QNY0, Q6QZQ4, Q8BP01, Q8C7U1, Q8CHW5, Q8K262, Q8N283, Q8N6Y0, Q8TAT2, Q8TER5, Q8TF21, Q91XV7

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

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1064 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38822625:C:A	donor_gain	1.0000
22:38826495:CCTA:C	donor_loss	1.0000
22:38826496:CTA:C	donor_loss	1.0000
22:38826497:TAC:T	donor_loss	1.0000
22:38826498:ACCTT:A	donor_loss	1.0000
22:38826499:C:A	donor_loss	1.0000
22:38826746:CC:C	acceptor_gain	1.0000
22:38826747:CC:C	acceptor_gain	1.0000
22:38826748:C:CC	acceptor_gain	1.0000
22:38828340:T:TA	donor_gain	1.0000
22:38843230:CTCA:C	donor_loss	1.0000
22:38843231:TCACC:T	donor_loss	1.0000
22:38843232:CA:C	donor_loss	1.0000
22:38843234:C:G	donor_loss	1.0000
22:38822677:A:AC	donor_gain	0.9900
22:38822678:C:CC	donor_gain	0.9900
22:38822685:T:TA	donor_gain	0.9900
22:38822686:C:A	donor_gain	0.9900
22:38822846:A:T	acceptor_gain	0.9900
22:38822849:A:T	acceptor_gain	0.9900
22:38823077:CCTTA:C	donor_loss	0.9900
22:38823078:CTTAC:C	donor_loss	0.9900
22:38823079:TTACC:T	donor_loss	0.9900
22:38823080:TA:T	donor_loss	0.9900
22:38823081:A:T	donor_loss	0.9900
22:38823082:CCTGC:C	donor_loss	0.9900
22:38826498:A:AC	donor_gain	0.9900
22:38826499:C:CC	donor_gain	0.9900
22:38826743:GGACC:G	acceptor_gain	0.9900
22:38826744:GACC:G	acceptor_gain	0.9900

AlphaMissense

3195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38822813:A:C	F433L	0.999
22:38822813:A:T	F433L	0.999
22:38822815:A:G	F433L	0.999
22:38823205:A:G	W386R	0.999
22:38823205:A:T	W386R	0.999
22:38823212:G:C	C383W	0.999
22:38822765:C:A	W449C	0.998
22:38822765:C:G	W449C	0.998
22:38822814:A:C	F433C	0.998
22:38823083:C:A	Q426H	0.998
22:38823083:C:G	Q426H	0.998
22:38823090:T:G	Q424P	0.998
22:38823109:C:A	G418W	0.998
22:38823189:C:T	G391D	0.998
22:38823203:C:A	W386C	0.998
22:38823203:C:G	W386C	0.998
22:38826583:A:G	S339P	0.998
22:38822687:C:A	W475C	0.997
22:38822687:C:G	W475C	0.997
22:38822814:A:G	F433S	0.997
22:38823089:C:A	Q424H	0.997
22:38823089:C:G	Q424H	0.997
22:38823093:C:T	G423D	0.997
22:38823189:C:A	G391V	0.997
22:38823213:C:T	C383Y	0.997
22:38823214:A:G	C383R	0.997
22:38826516:A:G	L361P	0.997
22:38826546:A:G	L351P	0.997
22:38826582:G:A	S339F	0.997
22:38826632:G:C	C322W	0.997

dbSNP variants (sampled 300 via entrez): RS1000002129 (22:38842385 T>G), RS1000123646 (22:38836563 C>T), RS1000129283 (22:38820014 G>A), RS1000160567 (22:38819791 T>A,C), RS1000189475 (22:38835407 G>A), RS1000290140 (22:38844149 T>A,G), RS1000313120 (22:38833442 C>G), RS1000323956 (22:38844411 A>C), RS1000387207 (22:38825640 C>T), RS1000464319 (22:38821419 C>T), RS1000557886 (22:38840151 T>C,G), RS1000661812 (22:38845826 T>C), RS1000816097 (22:38826978 C>T), RS1000843449 (22:38823548 G>A,T), RS1000885130 (22:38825881 C>T)

Disease associations

OMIM: gene MIM:609474 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002541_121	Menarche (age at onset)	3.000000e-08
GCST006585_593	Blood protein levels	5.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
bisphenol A	affects expression, decreases methylation	2
sodium arsenite	affects methylation, decreases expression	2
(+)-JQ1 compound	increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Bucladesine	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methotrexate	increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7NG	MKN1 NPTXR KO-1	Cancer cell line	Male
CVCL_C7NH	MKN1 NPTXR KO-2	Cancer cell line	Male

Clinical trials (associated diseases)

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