NXPH3

Summary

NXPH3 (neurexophilin 3, HGNC:8077) is a protein-coding gene on chromosome 17q21.33, encoding Neurexophilin-3 (O95157). May be signaling molecules that resemble neuropeptides.

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 11248 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_007225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8077
Approved symbol	NXPH3
Name	neurexophilin 3
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	NPH3
Ensembl gene	ENSG00000182575
Ensembl biotype	protein_coding
OMIM	604636
Entrez	11248

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000328741, ENST00000513748, ENST00000570453

RefSeq mRNA: 1 — MANE Select: NM_007225 NM_007225

CCDS: CCDS11550

Canonical transcript exons

ENST00000328741 — 2 exons

Exon	Start	End
ENSE00001303047	49578596	49583827
ENSE00001324660	49575871	49576273

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 91.83.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3691 / max 56.1065, expressed in 531 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161541	0.7209	351
161540	0.2312	89
161543	0.2239	101
161542	0.1931	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	91.83	gold quality
ascending aorta	UBERON:0001496	91.72	gold quality
thoracic aorta	UBERON:0001515	91.71	gold quality
descending thoracic aorta	UBERON:0002345	90.86	gold quality
aorta	UBERON:0000947	90.34	gold quality
vena cava	UBERON:0004087	90.31	silver quality
saphenous vein	UBERON:0007318	90.14	gold quality
right coronary artery	UBERON:0001625	89.60	gold quality
cerebellar hemisphere	UBERON:0002245	89.52	gold quality
cerebellar cortex	UBERON:0002129	89.51	gold quality
popliteal artery	UBERON:0002250	89.35	gold quality
tibial artery	UBERON:0007610	89.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.04	gold quality
cerebellum	UBERON:0002037	88.80	gold quality
pons	UBERON:0000988	87.20	gold quality
lateral nuclear group of thalamus	UBERON:0002736	85.87	gold quality
mucosa of stomach	UBERON:0001199	85.40	gold quality
subthalamic nucleus	UBERON:0001906	84.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.50	silver quality
superficial temporal artery	UBERON:0001614	84.36	gold quality
cardia of stomach	UBERON:0001162	84.28	gold quality
coronary artery	UBERON:0001621	83.59	gold quality
inferior vagus X ganglion	UBERON:0005363	83.54	gold quality
dorsal plus ventral thalamus	UBERON:0001897	83.50	gold quality
ventral tegmental area	UBERON:0002691	83.14	gold quality
left coronary artery	UBERON:0001626	82.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.80	gold quality
nipple	UBERON:0002030	82.11	gold quality
triceps brachii	UBERON:0001509	82.02	gold quality
gluteal muscle	UBERON:0002000	81.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

148 targeting NXPH3, 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-5193	100.00	67.26	1744
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4650-5P	99.98	64.69	999
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-545-3P	99.95	70.74	2783
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1976	99.74	65.48	1127

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nxph3	ENSDARG00000070694
mus_musculus	Nxph3	ENSMUSG00000046719
rattus_norvegicus	Nxph3	ENSRNOG00000005185

Paralogs (3): NXPH1 (ENSG00000122584), NXPH2 (ENSG00000144227), NXPH4 (ENSG00000182379)

Protein

Protein identifiers

Neurexophilin-3 — O95157 (reviewed: O95157)

All UniProt accessions (2): O95157, D6RGW2

UniProt curated annotations — full annotation on UniProt →

Function. May be signaling molecules that resemble neuropeptides. Ligand for alpha-neurexins.

Subcellular location. Secreted.

Tissue specificity. Highest level in brain.

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_009156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010450	Nxph	Family
IPR026845	NXPH/NXPE	Family

Pfam: PF06312

UniProt features (13 total): region of interest 5, glycosylation site 4, signal peptide 1, chain 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95157-F1	72.32	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): 137, 143, 62, 127

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): RNGTGGGC_UNKNOWN, MODULE_128, AP4_Q6, TAL1ALPHAE47_01, CAGCTG_AP4_Q5, SP1_Q2_01, HEN1_01, ZIC1_01, AACTTT_UNKNOWN, GATA2_01, PTF1BETA_Q6, GOMF_SIGNALING_RECEPTOR_BINDING, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, AP2_Q6_01, FOXO4_02

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

837 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXPH3	NRXN1	Q9ULB1	846
NXPH3	NGFR	P08138	455
NXPH3	SMIM28	A0A1B0GU29	435
NXPH3	GLRA2	P23416	418
NXPH3	TNNC2	P02585	413
NXPH3	PLEKHG7	Q6ZR37	412
NXPH3	LGI2	Q8N0V4	399
NXPH3	NRXN2	Q9P2S2	374
NXPH3	KCNS3	Q9BQ31	363
NXPH3	TMEM213	A2RRL7	361
NXPH3	CECR2	Q9BXF3	346
NXPH3	NETO2	Q8NC67	333
NXPH3	CLXN	Q9HAE3	327
NXPH3	KCNK4	Q9NYG8	318
NXPH3	AKNAD1	Q5T1N1	313

IntAct

11 interactions, top by confidence:

A	B	Type	Score
NXPH3	TUBA4A	psi-mi:“MI:0914”(association)	0.530
NXPH3	ABL1	psi-mi:“MI:0915”(physical association)	0.400
CRK	NXPH3	psi-mi:“MI:0915”(physical association)	0.400
NXPH3	SRC	psi-mi:“MI:0915”(physical association)	0.400
NXPH3	NCK1	psi-mi:“MI:0915”(physical association)	0.400
TAB1	NXPH3	psi-mi:“MI:0915”(physical association)	0.370
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
NXPH3	ACACB	psi-mi:“MI:0914”(association)	0.350
NXPH3	NXPH4	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): PALD1 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), SUFU (Affinity Capture-MS), LMF1 (Affinity Capture-MS), DCP2 (Affinity Capture-MS), SUFU (Affinity Capture-MS), PALD1 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), DCP2 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), NXPH3 (Negative Genetic), SUFU (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), LMF1 (Affinity Capture-MS)

ESM2 similar proteins: B2RZ42, E9PY61, F8W2C9, J3QPP8, O00253, O02695, O77559, O95157, P01311, P01313, P01322, P01323, P01325, P06306, P15473, P17936, P20959, P21743, P24591, P47876, P47878, P49192, P55107, P55108, P56388, P56722, P97737, Q08DX6, Q16568, Q16849, Q4RU86, Q58CS8, Q60673, Q62587, Q62865, Q68RJ9, Q6PRD1, Q6Q484, Q6S5C2, Q6UX46

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

278 predictions. Top by Δscore:

Variant	Effect	Δscore
17:49578593:TA:T	acceptor_loss	1.0000
17:49578594:A:AC	acceptor_loss	1.0000
17:49578594:A:AG	acceptor_gain	1.0000
17:49578595:G:GG	acceptor_gain	1.0000
17:49576028:G:T	donor_gain	0.9900
17:49576274:G:GG	donor_gain	0.9900
17:49578595:GGTC:G	acceptor_gain	0.9900
17:49576270:TCTG:T	donor_gain	0.9800
17:49578593:T:G	acceptor_gain	0.9800
17:49576271:CTG:C	donor_gain	0.9700
17:49578592:A:AG	acceptor_gain	0.9700
17:49578594:AG:A	acceptor_gain	0.9700
17:49578595:GG:G	acceptor_gain	0.9700
17:49578595:GGT:G	acceptor_gain	0.9700
17:49578595:GGTCA:G	acceptor_gain	0.9700
17:49576261:T:TA	donor_gain	0.9600
17:49576262:A:AA	donor_gain	0.9600
17:49576272:TG:T	donor_gain	0.9600
17:49576273:GG:G	donor_gain	0.9600
17:49577082:G:GT	donor_gain	0.9600
17:49577677:G:GT	donor_gain	0.9600
17:49578592:ATAG:A	acceptor_gain	0.9600
17:49576254:TGCA:T	donor_gain	0.9500
17:49576255:GCAG:G	donor_gain	0.9500
17:49576256:CAGG:C	donor_gain	0.9500
17:49576276:GAGTG:G	donor_loss	0.9500
17:49576151:G:GT	donor_gain	0.9400
17:49577316:GCA:G	donor_gain	0.9300
17:49577398:T:TA	donor_gain	0.9300
17:49577399:A:AA	donor_gain	0.9300

AlphaMissense

1650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:49578888:T:C	L116P	0.999
17:49578936:T:A	V132D	0.999
17:49579064:T:C	C175R	0.999
17:49579171:G:C	W210C	0.999
17:49579171:G:T	W210C	0.999
17:49579177:C:G	C212W	0.999
17:49579199:T:C	C220R	0.999
17:49579200:G:A	C220Y	0.999
17:49579201:T:G	C220W	0.999
17:49578894:T:A	V118D	0.998
17:49578899:G:T	G120W	0.998
17:49578900:G:A	G120E	0.998
17:49578974:T:C	S145P	0.998
17:49579010:T:C	F157L	0.998
17:49579011:T:G	F157C	0.998
17:49579012:C:A	F157L	0.998
17:49579012:C:G	F157L	0.998
17:49579064:T:A	C175S	0.998
17:49579065:G:A	C175Y	0.998
17:49579065:G:C	C175S	0.998
17:49579066:C:G	C175W	0.998
17:49579169:T:A	W210R	0.998
17:49579169:T:C	W210R	0.998
17:49579175:T:A	C212S	0.998
17:49579175:T:C	C212R	0.998
17:49579176:G:A	C212Y	0.998
17:49579176:G:C	C212S	0.998
17:49579236:T:C	L232P	0.998
17:49579250:T:C	C237R	0.998
17:49579251:G:A	C237Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000060935 (17:49582385 C>T), RS1000068528 (17:49577004 G>C), RS1000222754 (17:49581233 G>T), RS1000349968 (17:49575384 G>T), RS1000568411 (17:49580081 C>G), RS1000847044 (17:49575916 C>A,T), RS1001253523 (17:49574578 C>T), RS1001336817 (17:49576310 G>A), RS1001403147 (17:49580891 T>C), RS1001688734 (17:49581123 A>C), RS1002181852 (17:49581797 C>G,T), RS1002613527 (17:49580834 T>A), RS1002807190 (17:49578406 T>C,G), RS1003084257 (17:49574109 G>A), RS1003346541 (17:49578463 G>A)

Disease associations

OMIM: gene MIM:604636 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	4
trichostatin A	affects expression, decreases expression	2
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
beta-lapachone	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
CGP 52608	increases reaction, affects binding	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Diazinon	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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