NXPH2

Summary

NXPH2 (neurexophilin 2, HGNC:8076) is a protein-coding gene on chromosome 2q22.1, encoding Neurexophilin-2 (O95156). May be signaling molecules that resemble neuropeptides and that act by binding to alpha-neurexins and possibly other receptors.

Predicted to enable signaling receptor binding activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to be located in extracellular region.

Source: NCBI Gene 11249 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_007226

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8076
Approved symbol	NXPH2
Name	neurexophilin 2
Location	2q22.1
Locus type	gene with protein product
Status	Approved
Aliases	NPH2
Ensembl gene	ENSG00000144227
Ensembl biotype	protein_coding
OMIM	604635
Entrez	11249

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000272641

RefSeq mRNA: 1 — MANE Select: NM_007226 NM_007226

CCDS: CCDS46421

Canonical transcript exons

ENST00000272641 — 2 exons

Exon	Start	End
ENSE00000964114	138669157	138671665
ENSE00001772681	138780191	138780390

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 86.27.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8025 / max 118.3103, expressed in 218 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30837	0.2900	129
30840	0.1758	78
30836	0.1516	66
30835	0.0951	48
30839	0.0544	28
30838	0.0356	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	86.27	gold quality
prefrontal cortex	UBERON:0000451	76.67	gold quality
embryo	UBERON:0000922	73.01	gold quality
ganglionic eminence	UBERON:0004023	73.01	gold quality
ventricular zone	UBERON:0003053	72.71	gold quality
cortical plate	UBERON:0005343	72.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.93	gold quality
anterior cingulate cortex	UBERON:0009835	70.10	gold quality
middle temporal gyrus	UBERON:0002771	69.75	silver quality
neocortex	UBERON:0001950	69.34	gold quality
frontal cortex	UBERON:0001870	69.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	68.63	gold quality
germinal epithelium of ovary	UBERON:0001304	67.95	gold quality
endothelial cell	CL:0000115	67.92	gold quality
Brodmann (1909) area 46	UBERON:0006483	67.56	gold quality
cerebral cortex	UBERON:0000956	66.56	gold quality
left ovary	UBERON:0002119	66.33	gold quality
primary visual cortex	UBERON:0002436	66.06	gold quality
ovary	UBERON:0000992	65.46	gold quality
sperm	CL:0000019	65.29	gold quality
adult mammalian kidney	UBERON:0000082	65.02	gold quality
right frontal lobe	UBERON:0002810	64.85	gold quality
superior vestibular nucleus	UBERON:0007227	64.84	silver quality
occipital lobe	UBERON:0002021	63.67	gold quality
amygdala	UBERON:0001876	61.52	gold quality
superior frontal gyrus	UBERON:0002661	60.35	gold quality
forebrain	UBERON:0001890	59.99	gold quality
temporal lobe	UBERON:0001871	58.87	gold quality
right ovary	UBERON:0002118	58.65	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	42.10
E-ANND-3	no	2.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting NXPH2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
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-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Literature-anchored findings (GeneRIF, showing 1)

• expression inversely correlated with N stage in pancreatic ductal adenocarcinoma (PMID:27817196)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nxph2a	ENSDARG00000063224
mus_musculus	Nxph2	ENSMUSG00000069132
rattus_norvegicus	Nxph2	ENSRNOG00000040333

Paralogs (3): NXPH1 (ENSG00000122584), NXPH4 (ENSG00000182379), NXPH3 (ENSG00000182575)

Protein

Protein identifiers

Neurexophilin-2 — O95156 (reviewed: O95156)

All UniProt accessions (1): O95156

UniProt curated annotations — full annotation on UniProt →

Function. May be signaling molecules that resemble neuropeptides and that act by binding to alpha-neurexins and possibly other receptors.

Subcellular location. Secreted.

Tissue specificity. Expressed in brain and kidney.

Post-translational modifications. May be proteolytically processed at the boundary between the N-terminal non-conserved and the central conserved domain in neuron-like cells.

Similarity. Belongs to the neurexophilin family.

RefSeq proteins (1): NP_009157* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010450	Nxph	Family
IPR026845	NXPH/NXPE	Family

Pfam: PF06312

UniProt features (11 total): region of interest 4, glycosylation site 4, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95156-F1	68.20	0.34

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 (4): 86, 139, 149, 155

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): GERY_CEBP_TARGETS, chr2q22, KOYAMA_SEMA3B_TARGETS_UP, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, GOMF_SIGNALING_RECEPTOR_BINDING, MORF_ATF2, ROVERSI_GLIOMA_COPY_NUMBER_DN, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_DN, MODULE_49, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, CAHOY_NEURONAL, MIR520D_5P

GO Biological Process (1): neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (1): signaling receptor binding (GO:0005102)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	1
protein binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

737 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXPH2	NRXN1	Q9ULB1	821
NXPH2	OVCA2	Q8WZ82	543
NXPH2	APBA1	Q02410	531
NXPH2	HMX2	A2RU54	521
NXPH2	TMEM86A	Q8N2M4	514
NXPH2	DPH1	Q9BZG8	492
NXPH2	SEPTIN9	Q9UHD8	490
NXPH2	SPOPL	Q6IQ16	473
NXPH2	SYT13	Q7L8C5	428
NXPH2	OR5K2	Q8NHB8	419
NXPH2	FAM135B	Q49AJ0	410
NXPH2	LRRC3C	A6NJW4	407
NXPH2	NMRAL1	Q9HBL8	398
NXPH2	C15orf40	Q8WUR7	394
NXPH2	THSD7B	Q9C0I4	373

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NXPH2	PCDH7	psi-mi:“MI:0914”(association)	0.350
NXPH2	B4GALT5	psi-mi:“MI:0914”(association)	0.350
NXPH2	VGF	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): CELSR1 (Affinity Capture-MS), FAT1 (Affinity Capture-MS), FREM2 (Affinity Capture-MS), UBR1 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), PCDH9 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), PCDH7 (Affinity Capture-MS), MADD (Affinity Capture-MS), UBR2 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), TAF7 (Affinity Capture-MS), STAT3 (Affinity Capture-MS)

ESM2 similar proteins: A1XQX1, A2ATD1, B2RZ42, D4A6L0, O00451, O08842, O13097, O13156, O13157, O93512, O95156, O95980, P0DJQ9, P15473, P17936, P20959, P21744, P22692, P24854, P47878, P47879, P52796, P56159, P58659, P97785, Q05716, Q17QD6, Q28145, Q28893, Q58CS8, Q5E9X0, Q5RAD6, Q5T848, Q62997, Q6PCX7, Q6PFE7, Q6S5C2, Q7TQ33, Q80UG6, Q8C419

Diamond homologs: O95156, O95157, O95158, P58417, Q28145, Q5E9M6, Q5R530, Q61199, Q61200, Q63366, Q8WMI6, Q8WMJ4, Q8WMJ7, Q91VX5, Q9Z2N4, Q9Z2N5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

726 predictions. Top by Δscore:

Variant	Effect	Δscore
2:138671661:AATAG:A	acceptor_gain	1.0000
2:138671662:ATAG:A	acceptor_gain	1.0000
2:138671663:TAG:T	acceptor_gain	1.0000
2:138671664:AG:A	acceptor_gain	1.0000
2:138671665:GC:G	acceptor_loss	1.0000
2:138671666:C:CC	acceptor_gain	1.0000
2:138671670:T:C	acceptor_gain	1.0000
2:138671670:T:TC	acceptor_gain	1.0000
2:138780184:CACT:C	donor_loss	1.0000
2:138780185:ACTC:A	donor_loss	1.0000
2:138780186:CTCA:C	donor_loss	1.0000
2:138780187:TCA:T	donor_loss	1.0000
2:138780188:CA:C	donor_loss	1.0000
2:138780189:A:AC	donor_gain	1.0000
2:138780189:A:AT	donor_loss	1.0000
2:138780190:C:CC	donor_gain	1.0000
2:138780190:C:CT	donor_loss	1.0000
2:138780190:CCAG:C	donor_gain	1.0000
2:138671668:G:C	acceptor_gain	0.9900
2:138671668:G:GC	acceptor_gain	0.9900
2:138671669:T:C	acceptor_gain	0.9900
2:138671669:T:TC	acceptor_gain	0.9900
2:138682430:T:TC	acceptor_gain	0.9900
2:138671662:ATAGC:A	acceptor_gain	0.9800
2:138671663:TAGC:T	acceptor_gain	0.9800
2:138671664:AGCTG:A	acceptor_gain	0.9800
2:138671665:GCTG:G	acceptor_gain	0.9800
2:138780090:C:A	donor_gain	0.9800
2:138780189:AC:A	donor_gain	0.9800
2:138780190:CC:C	donor_gain	0.9800

AlphaMissense

1734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:138670968:G:T	P250H	1.000
2:138670970:G:C	C249W	1.000
2:138670971:C:G	C249S	1.000
2:138670971:C:T	C249Y	1.000
2:138670972:A:G	C249R	1.000
2:138670972:A:T	C249S	1.000
2:138670986:A:G	L244P	1.000
2:138671006:A:C	F237L	1.000
2:138671006:A:T	F237L	1.000
2:138671008:A:G	F237L	1.000
2:138671021:G:C	C232W	1.000
2:138671022:C:A	C232F	1.000
2:138671022:C:G	C232S	1.000
2:138671022:C:T	C232Y	1.000
2:138671023:A:G	C232R	1.000
2:138671023:A:T	C232S	1.000
2:138671045:G:C	C224W	1.000
2:138671046:C:A	C224F	1.000
2:138671046:C:G	C224S	1.000
2:138671046:C:T	C224Y	1.000
2:138671047:A:G	C224R	1.000
2:138671047:A:T	C224S	1.000
2:138671051:C:A	W222C	1.000
2:138671051:C:G	W222C	1.000
2:138671053:A:G	W222R	1.000
2:138671053:A:T	W222R	1.000
2:138671084:G:C	C211W	1.000
2:138671085:C:G	C211S	1.000
2:138671085:C:T	C211Y	1.000
2:138671086:A:G	C211R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000247 (2:138779427 A>C,G,T), RS1000010733 (2:138735477 A>C,G), RS1000014753 (2:138721479 A>G,T), RS1000056237 (2:138738469 T>C), RS1000058245 (2:138781005 T>A,C), RS1000070775 (2:138716162 G>A,T), RS1000133110 (2:138735174 A>T), RS1000160911 (2:138758421 C>A,T), RS1000201758 (2:138761276 A>C,G), RS1000219987 (2:138673125 T>C), RS1000226962 (2:138743767 T>C), RS1000253989 (2:138761087 C>A), RS1000259327 (2:138700129 T>C), RS1000266080 (2:138719193 GAT>G), RS1000275108 (2:138758185 A>G)

Disease associations

OMIM: gene MIM:604635 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000412_5	Male infertility	9.000000e-07
GCST001254_2	Alcohol dependence	8.000000e-06
GCST003139_13	Glomerular filtration rate in chronic kidney disease	5.000000e-06
GCST005156_1	Alloimmunization response to pregnancy (HLA class I)	2.000000e-08
GCST008476_18	Emphysema annual change measurement in smokers (percent low attenuation area)	9.000000e-08
GCST009391_1384	Metabolite levels	3.000000e-06
GCST009391_893	Metabolite levels	5.000000e-06
GCST012462_2	Asthma and eczema	5.000000e-06
GCST012490_647	Femur bone mineral density x serum urate levels interaction	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008462	pregnancy induced alloimmunization
EFO:0007626	emphysema imaging measurement
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement
EFO:0010440	triacylglycerol 58:6 measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Phenylmercuric Acetate	increases expression, affects cotreatment	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	increases expression	1
belinostat	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Niclosamide	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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