NXPH4

Summary

NXPH4 (neurexophilin 4, HGNC:8078) is a protein-coding gene on chromosome 12q13.3, encoding Neurexophilin-4 (O95158). 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. Predicted to be active in GABA-ergic synapse.

Source: NCBI Gene 11247 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_007224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8078
Approved symbol	NXPH4
Name	neurexophilin 4
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	NPH4
Ensembl gene	ENSG00000182379
Ensembl biotype	protein_coding
OMIM	604637
Entrez	11247

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000349394, ENST00000555154, ENST00000556415

RefSeq mRNA: 1 — MANE Select: NM_007224 NM_007224

CCDS: CCDS8933

Canonical transcript exons

ENST00000349394 — 2 exons

Exon	Start	End
ENSE00001318640	57216794	57217026
ENSE00002514274	57224878	57226449

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 86.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2117 / max 108.7133, expressed in 1064 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126175	3.0302	1038
126177	0.0993	33
126178	0.0665	21
126176	0.0157	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	86.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.84	gold quality
cerebellar hemisphere	UBERON:0002245	82.38	gold quality
skin of abdomen	UBERON:0001416	82.30	gold quality
cerebellar cortex	UBERON:0002129	82.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.25	gold quality
skin of leg	UBERON:0001511	81.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.29	silver quality
cerebellum	UBERON:0002037	80.29	gold quality
zone of skin	UBERON:0000014	79.58	gold quality
hair follicle	UBERON:0002073	79.43	gold quality
cortical plate	UBERON:0005343	79.43	gold quality
upper arm skin	UBERON:0004263	78.46	gold quality
secondary oocyte	CL:0000655	76.42	silver quality
stromal cell of endometrium	CL:0002255	73.68	gold quality
cervix squamous epithelium	UBERON:0006922	73.60	gold quality
embryo	UBERON:0000922	72.87	gold quality
apex of heart	UBERON:0002098	70.90	gold quality
prefrontal cortex	UBERON:0000451	69.84	gold quality
lower esophagus mucosa	UBERON:0035834	69.75	gold quality
ventricular zone	UBERON:0003053	69.52	gold quality
pancreatic ductal cell	CL:0002079	69.29	silver quality
skin of hip	UBERON:0001554	68.83	gold quality
cartilage tissue	UBERON:0002418	67.79	silver quality
CA1 field of hippocampus	UBERON:0003881	67.52	gold quality
cerebellar vermis	UBERON:0004720	67.18	gold quality
minor salivary gland	UBERON:0001830	66.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	66.10	gold quality
frontal cortex	UBERON:0001870	65.75	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	65.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting NXPH4, 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-4692	100.00	67.32	2066
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-1224-3P	97.24	65.92	851
HSA-MIR-6515-5P	97.08	65.48	1219

Literature-anchored findings (GeneRIF, showing 2)

• A novel EZH2/NXPH4/CDKN2A axis is involved in regulating the proliferation and migration of non-small cell lung cancer cells. (PMID:34919637)
• Neurexophilin 4 is a prognostic biomarker correlated with immune infiltration in bladder cancer. (PMID:35758021)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nxph4	ENSMUSG00000040258
rattus_norvegicus	Nxph4	ENSRNOG00000025059

Paralogs (3): NXPH1 (ENSG00000122584), NXPH2 (ENSG00000144227), NXPH3 (ENSG00000182575)

Protein

Protein identifiers

Neurexophilin-4 — O95158 (reviewed: O95158)

All UniProt accessions (2): G3V5C5, O95158

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, spleen, and testis.

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_009155* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010450	Nxph	Family
IPR026845	NXPH/NXPE	Family

Pfam: PF06312

UniProt features (15 total): region of interest 5, glycosylation site 4, sequence conflict 3, signal peptide 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95158-F1	62.29	0.15

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): 143, 149, 72, 133

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): CREL_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BENPORATH_ES_WITH_H3K27ME3, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_255, MODULE_317, AREB6_01, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, AP2_Q3, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, SP1_Q2_01, GOBP_CELL_CELL_SIGNALING, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (2): neuropeptide signaling pathway (GO:0007218), modulation of chemical synaptic transmission (GO:0050804)

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

GO Cellular Component (3): extracellular region (GO:0005576), GABA-ergic synapse (GO:0098982), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
protein binding	1
cellular anatomical structure	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXPH4	NRXN1	Q9ULB1	893
NXPH4	NRXN2	Q9P2S2	602
NXPH4	CPLX3	Q8WVH0	559
NXPH4	GPATCH4	Q5T3I0	484
NXPH4	TMEM52	Q8NDY8	480
NXPH4	CABP7	Q86V35	464
NXPH4	NRSN2	Q9GZP1	462
NXPH4	SINHCAF	Q9NP50	444
NXPH4	RASSF8	Q8NHQ8	423
NXPH4	KCNG4	Q8TDN1	407
NXPH4	SLC17A6	Q9P2U8	377
NXPH4	PLEKHA2	Q9HB19	373
NXPH4	C1QL2	Q7Z5L3	371
NXPH4	NPHP4	O75161	370
NXPH4	NOS1AP	O75052	354

IntAct

38 interactions, top by confidence:

A	B	Type	Score
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
MMP26	SLC25A20	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
MFAP4	CRLF1	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
NAGA	TMEM223	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
CST9L	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350
LY86	PLXNB2	psi-mi:“MI:0914”(association)	0.350
SFTPA2	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
PON2	ENTPD6	psi-mi:“MI:0914”(association)	0.350
EFNA2	C1QL1	psi-mi:“MI:0914”(association)	0.350
LCN9	C1QL1	psi-mi:“MI:0914”(association)	0.350
LY6H	NXPH4	psi-mi:“MI:0914”(association)	0.350
PCDHB3	ESYT2	psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
EPHA7	PLOD2	psi-mi:“MI:0914”(association)	0.350
OIT3	WNT10B	psi-mi:“MI:0914”(association)	0.350
ECEL1	ADAM10	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Reconstituted Complex), NXPH4 (Affinity Capture-MS), NXPH4 (Reconstituted Complex), NXPH4 (Affinity Capture-RNA), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), NXPH4 (Affinity Capture-MS)

ESM2 similar proteins: A2ATD1, B1AKI9, B2RZ42, D4A6L0, O00451, O08842, O13157, O14795, O95156, O95157, O95158, P0DJQ9, P17863, P56159, P58417, P97785, Q0VGY8, Q28145, Q4KUS2, Q5E9M6, Q5E9X0, Q5F3L9, Q5QQ49, Q5QQ50, Q5QQ51, Q5QQ56, Q5QQ57, Q5R530, Q5RAD6, Q61199, Q61200, Q62768, Q62769, Q62997, Q63366, Q811B1, Q86Y38, Q8BJQ9, Q8N3T6, Q8QFV1

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	9	6.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

227 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57217025:AGG:A	donor_loss	1.0000
12:57217026:GGT:G	donor_loss	1.0000
12:57217022:GGAAG:G	donor_gain	0.9900
12:57217023:GAAGG:G	donor_gain	0.9900
12:57217024:A:T	donor_gain	0.9900
12:57217028:T:A	donor_loss	0.9900
12:57217023:GAAG:G	donor_gain	0.9800
12:57217027:G:GG	donor_gain	0.9800
12:57224875:CAGGC:C	acceptor_loss	0.9800
12:57224876:A:AC	acceptor_loss	0.9800
12:57224876:A:AG	acceptor_gain	0.9800
12:57224877:G:GC	acceptor_loss	0.9800
12:57224877:G:GG	acceptor_gain	0.9800
12:57224877:GGCC:G	acceptor_gain	0.9800
12:57224871:T:TA	acceptor_gain	0.9700
12:57224874:ACAG:A	acceptor_gain	0.9700
12:57224875:C:G	acceptor_gain	0.9700
12:57217025:AG:A	donor_gain	0.9600
12:57217026:GG:G	donor_gain	0.9600
12:57224869:C:CA	acceptor_gain	0.9600
12:57224874:A:AG	acceptor_gain	0.9600
12:57221368:G:GA	donor_gain	0.9500
12:57217024:AAG:A	donor_gain	0.8800
12:57221367:T:TA	donor_gain	0.8800
12:57224876:AG:A	acceptor_gain	0.8800
12:57224877:GG:G	acceptor_gain	0.8800
12:57217654:G:T	donor_gain	0.8700
12:57224869:C:A	acceptor_loss	0.8700
12:57224877:GGC:G	acceptor_gain	0.8600
12:57216985:G:GT	donor_gain	0.8200

AlphaMissense

1970 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57225144:G:C	W108C	1.000
12:57225144:G:T	W108C	1.000
12:57225239:T:C	F140S	1.000
12:57225275:T:A	V152D	1.000
12:57225622:T:A	W268R	1.000
12:57225622:T:C	W268R	1.000
12:57225624:G:C	W268C	1.000
12:57225624:G:T	W268C	1.000
12:57225628:T:C	C270R	1.000
12:57225629:G:A	C270Y	1.000
12:57225630:T:G	C270W	1.000
12:57225652:T:C	C278R	1.000
12:57225653:G:A	C278Y	1.000
12:57225654:T:G	C278W	1.000
12:57225703:T:C	C295R	1.000
12:57225704:G:A	C295Y	1.000
12:57225705:C:G	C295W	1.000
12:57225142:T:A	W108R	0.999
12:57225142:T:C	W108R	0.999
12:57225145:G:T	G109W	0.999
12:57225151:T:C	F111L	0.999
12:57225153:C:A	F111L	0.999
12:57225153:C:G	F111L	0.999
12:57225179:T:C	F120S	0.999
12:57225185:T:C	L122P	0.999
12:57225196:G:C	G126R	0.999
12:57225197:G:A	G126D	0.999
12:57225203:T:A	I128N	0.999
12:57225203:T:G	I128S	0.999
12:57225209:A:T	D130V	0.999

dbSNP variants (sampled 300 via entrez): RS1000858428 (12:57222532 A>C,T), RS1000960402 (12:57215859 C>A), RS1001031318 (12:57221429 TG>T,TGG), RS1001360971 (12:57222106 C>T), RS1001796876 (12:57215158 G>C,T), RS1001981910 (12:57226026 C>A,T), RS1002292889 (12:57221834 T>C), RS1002621296 (12:57216357 G>A), RS1002717547 (12:57217389 G>A), RS1002858079 (12:57224929 C>T), RS1002961079 (12:57219575 C>T), RS1003156326 (12:57223023 G>A), RS1003294520 (12:57220612 A>T), RS1003495257 (12:57226142 C>G,T), RS1003593071 (12:57222876 G>A)

Disease associations

OMIM: gene MIM:604637 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002539_15	Schizophrenia	2.000000e-12
GCST003992_42	Photic sneeze reflex	1.000000e-15
GCST004521_233	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST006803_97	Schizophrenia	3.000000e-11
GCST008154_75	Trunk fat mass	7.000000e-06
GCST008916_2	Asthma	2.000000e-08
GCST009600_112	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	6.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome

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
Particulate Matter	decreases expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
trichostatin A	affects expression	1
beta-lapachone	increases expression, decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Resveratrol	increases expression, affects cotreatment	1
Decitabine	decreases expression, affects reaction	1
Aldehydes	increases expression	1
Copper	affects cotreatment, increases expression	1
Dexamethasone	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Niclosamide	increases expression	1
Oxygen	increases expression	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Zinc	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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