NXPE3

Summary

NXPE3 (neurexophilin and PC-esterase domain family member 3, HGNC:28238) is a protein-coding gene on chromosome 3q12.3, encoding NXPE family member 3 (Q969Y0).

This gene encodes a member of the neurexophilin family of neuropeptide-like glycoproteins. The encoded protein contains a variable N-terminal domain, a highly conserved neurexophilin and PC-esterase (NXPE) central domain, a short linker region, and a cysteine-rich C-terminal domain. This protein binds alpha neurexins, a group of presynaptic transmembrane receptors that promote adhesion between dendrites and axons. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 91775 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total
• MANE Select transcript: NM_145037

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28238
Approved symbol	NXPE3
Name	neurexophilin and PC-esterase domain family member 3
Location	3q12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC15606
Ensembl gene	ENSG00000144815
Ensembl biotype	protein_coding
Entrez	91775

Gene structure

Transcript identifiers

Ensembl transcripts: 67 — 53 protein_coding, 13 nonsense_mediated_decay, 1 retained_intron

ENST00000273347, ENST00000474165, ENST00000477909, ENST00000487830, ENST00000491511, ENST00000495842, ENST00000704528, ENST00000704529, ENST00000704530, ENST00000704531, ENST00000704532, ENST00000704533, ENST00000704534, ENST00000704535, ENST00000704536, ENST00000704537, ENST00000704538, ENST00000704539, ENST00000704540, ENST00000704541, ENST00000704542, ENST00000704543, ENST00000704544, ENST00000704545, ENST00000704546, ENST00000704547, ENST00000704548, ENST00000704549, ENST00000704550, ENST00000704551, ENST00000704552, ENST00000704553, ENST00000705586, ENST00000879314, ENST00000879315, ENST00000879316, ENST00000879317, ENST00000879318, ENST00000925276, ENST00000925277, ENST00000925278, ENST00000925279, ENST00000925280, ENST00000925281, ENST00000969175, ENST00000969176, ENST00000969177, ENST00000969178, ENST00000969179, ENST00000969180, ENST00000969181, ENST00000969182, ENST00000969183, ENST00000969184, ENST00000969185, ENST00000969186, ENST00000969187, ENST00000969188, ENST00000969189, ENST00000969190, ENST00000969191, ENST00000969192, ENST00000969193, ENST00000969194, ENST00000969195, ENST00000969196, ENST00000969197

RefSeq mRNA: 11 — MANE Select: NM_145037 NM_001134456, NM_001348990, NM_001348991, NM_001348992, NM_001348993, NM_001348994, NM_001348995, NM_001348996, NM_001348997, NM_001348998, NM_145037

CCDS: CCDS2945, CCDS93338

Canonical transcript exons

ENST00000273347 — 8 exons

Exon	Start	End
ENSE00000967279	101807053	101807126
ENSE00001014457	101821404	101828231
ENSE00001161968	101801235	101801989
ENSE00001249029	101785402	101785689
ENSE00001517424	101782660	101782780
ENSE00001944207	101782110	101782290
ENSE00003991785	101816795	101817001
ENSE00003991820	101779211	101779324

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 94.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4351 / max 271.3708, expressed in 1736 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37653	3.8702	1557
37656	3.7008	1132
37654	2.5867	1278
37655	1.1104	663
37658	0.0904	28
37657	0.0473	15
37659	0.0293	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.02	gold quality
inferior vagus X ganglion	UBERON:0005363	93.47	gold quality
corpus callosum	UBERON:0002336	92.55	gold quality
subthalamic nucleus	UBERON:0001906	91.74	gold quality
gastrocnemius	UBERON:0001388	91.10	gold quality
muscle of leg	UBERON:0001383	91.06	gold quality
pons	UBERON:0000988	90.91	gold quality
superior vestibular nucleus	UBERON:0007227	90.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.38	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.02	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.78	gold quality
monocyte	CL:0000576	88.71	gold quality
leukocyte	CL:0000738	88.50	gold quality
mononuclear cell	CL:0000842	88.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.44	gold quality
skeletal muscle organ	UBERON:0014892	88.23	gold quality
muscle organ	UBERON:0001630	88.21	gold quality
lateral globus pallidus	UBERON:0002476	87.95	gold quality
substantia nigra pars compacta	UBERON:0001965	87.63	gold quality
ventral tegmental area	UBERON:0002691	87.49	gold quality
stromal cell of endometrium	CL:0002255	87.08	gold quality
biceps brachii	UBERON:0001507	86.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.42	gold quality
bone marrow cell	CL:0002092	85.18	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.75	gold quality
adrenal tissue	UBERON:0018303	84.24	gold quality
right atrium auricular region	UBERON:0006631	83.73	gold quality
medulla oblongata	UBERON:0001896	83.72	gold quality
granulocyte	CL:0000094	83.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

203 targeting NXPE3, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-518E-5P	100.00	67.66	954
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-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nxpe3	ENSDARG00000061690
mus_musculus	Nxpe3	ENSMUSG00000075033
rattus_norvegicus	Nxpe3	ENSRNOG00000001608

Paralogs (3): NXPE1 (ENSG00000095110), NXPE4 (ENSG00000137634), NXPE2 (ENSG00000204361)

Protein

Protein identifiers

NXPE family member 3 — Q969Y0 (reviewed: Q969Y0)

Alternative names: Protein FAM55C

All UniProt accessions (15): Q969Y0, A0A994J4P4, A0A994J4P8, A0A994J4Q2, A0A994J4Q6, A0A994J544, A0A994J548, A0A994J553, A0A994J732, A0A994J736, A0A994J739, A0A994J7H3, A0A994J7H7, A0A994J7U7, C9K0A9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the NXPE family.

RefSeq proteins (11): NP_001127928, NP_001335919, NP_001335920, NP_001335921, NP_001335922, NP_001335923, NP_001335924, NP_001335925, NP_001335926, NP_001335927, NP_659474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014756	Ig_E-set	Homologous_superfamily
IPR026845	NXPH/NXPE	Family
IPR057106	NXPE4_C	Domain

Pfam: PF06312, PF24536

UniProt features (6 total): glycosylation site 3, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969Y0-F1	89.88	0.79

Functional residue map

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

Glycosylation sites (3): 237, 292, 346

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): MORF_FLT1, MORF_MSH3, MORF_BRCA1, MORF_ESR1, BEIER_GLIOMA_STEM_CELL_DN, MORF_RAD51L3, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, MORF_ETV3, VDR_Q3, MORF_ATF2, MORF_BCL2L11, MORF_PRKACA, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, COLDREN_GEFITINIB_RESISTANCE_UP

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXPE3	LRRC37A2	A6NM11	507
NXPE3	ZNF154	Q13106	479
NXPE3	PLEKHA4	Q9H4M7	472
NXPE3	RPP38	P78345	461
NXPE3	ZNF611	Q8N823	455
NXPE3	ARL17B	I3L3L1	447
NXPE3	MAP9	Q49MG5	447
NXPE3	ARL17A	Q8IVW1	445
NXPE3	ZBTB11	O95625	400
NXPE3	CEP97	Q8IW35	400
NXPE3	RSPH9	Q9H1X1	397
NXPE3	LRRC37A	A6NMS7	393
NXPE3	LRRC37A3	O60309	391
NXPE3	NOX5	Q96PH1	370
NXPE3	SLC6A20	Q9NP91	361

IntAct

57 interactions, top by confidence:

A	B	Type	Score
NXPE3		psi-mi:“MI:0915”(physical association)	0.560
ERVFRD-1	NXPE3	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	NXPE3	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	NXPE3	psi-mi:“MI:0915”(physical association)	0.560
	NXPE3	psi-mi:“MI:0915”(physical association)	0.560
MRM1	NXPE3	psi-mi:“MI:0915”(physical association)	0.560
SYT12	B4GALT5	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
NXPE3	OS9	psi-mi:“MI:0915”(physical association)	0.500
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	MAP2K7	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
HTR3B	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	POTEF	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), NXPE3 (Affinity Capture-RNA), NXPE3 (Affinity Capture-RNA), NXPE3 (Two-hybrid), NXPE3 (Two-hybrid), CASC4 (Two-hybrid), ERVFRD-1 (Two-hybrid), MRM1 (Two-hybrid)

ESM2 similar proteins: A2VDP6, A4D0V7, B1WB06, F1N2K1, O43548, P06802, P15396, P22413, P50127, P79949, P97259, Q05004, Q08834, Q08BN9, Q09328, Q14C87, Q14DG7, Q2TU62, Q3L7M0, Q3U095, Q52KP5, Q5R748, Q5RCA5, Q5XI89, Q5ZLK4, Q6AX23, Q6DNG6, Q6UWF7, Q6ZXA0, Q76HP2, Q76HP3, Q86UX2, Q8BG22, Q8C7K6, Q8K1B9, Q8N323, Q8NCG5, Q8NHY0, Q8R4G6, Q8VI38

Diamond homologs: A2VDP6, Q05004, Q08BN9, Q3U095, Q52KP5, Q5RCA5, Q5XI89, Q6UWF7, Q8N323, Q969Y0, Q96DL1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1908 predictions. Top by Δscore:

Variant	Effect	Δscore
3:101801233:A:AG	acceptor_gain	1.0000
3:101801234:G:GA	acceptor_gain	1.0000
3:101807049:AAAGT:A	acceptor_gain	1.0000
3:101779321:GGAG:G	donor_gain	0.9900
3:101779322:GAGG:G	donor_gain	0.9900
3:101779325:G:A	donor_loss	0.9900
3:101779326:T:G	donor_loss	0.9900
3:101782224:A:T	donor_gain	0.9900
3:101801229:CTTCA:C	acceptor_loss	0.9900
3:101801230:TTCAG:T	acceptor_loss	0.9900
3:101801231:TCAG:T	acceptor_loss	0.9900
3:101801232:CA:C	acceptor_loss	0.9900
3:101801233:A:AT	acceptor_loss	0.9900
3:101801234:GT:G	acceptor_gain	0.9900
3:101801234:GTA:G	acceptor_gain	0.9900
3:101801234:GTACT:G	acceptor_gain	0.9900
3:101801552:G:GT	donor_gain	0.9900
3:101807050:AAGT:A	acceptor_gain	0.9900
3:101807051:AGT:A	acceptor_gain	0.9900
3:101807052:GTG:G	acceptor_gain	0.9900
3:101816968:C:T	donor_gain	0.9900
3:101821399:TTCA:T	acceptor_loss	0.9900
3:101821401:CAGAT:C	acceptor_loss	0.9900
3:101821402:A:AG	acceptor_gain	0.9900
3:101821402:A:C	acceptor_loss	0.9900
3:101821403:G:GG	acceptor_gain	0.9900
3:101779322:GAG:G	donor_gain	0.9800
3:101779325:G:GG	donor_gain	0.9800
3:101801234:GTAC:G	acceptor_gain	0.9800
3:101807051:A:G	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000049659 (3:101800571 C>T), RS1000101115 (3:101779402 C>A,T), RS1000240219 (3:101806595 T>A,G), RS1000344040 (3:101813954 A>AT), RS1000389583 (3:101826707 G>A), RS1000394977 (3:101814220 G>A,C), RS1000483701 (3:101781495 A>G), RS1000525263 (3:101820798 C>T), RS1000537403 (3:101827838 C>G,T), RS1000565734 (3:101807509 A>G), RS1000587896 (3:101788213 C>A,T), RS1000619109 (3:101787939 G>A), RS1000688250 (3:101801601 C>T), RS1000857933 (3:101787267 T>G), RS1000860077 (3:101808209 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression, affects expression	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
Benzo(a)pyrene	increases expression	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	3
mercuric bromide	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Cadmium Chloride	increases abundance, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
gadodiamide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Temozolomide	decreases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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