NXPE4

Summary

NXPE4 (neurexophilin and PC-esterase domain family member 4, HGNC:23117) is a protein-coding gene on chromosome 11q23.2, encoding NXPE family member 4 (Q6UWF7).

Located in extracellular exosome.

Source: NCBI Gene 54827 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001077639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23117
Approved symbol	NXPE4
Name	neurexophilin and PC-esterase domain family member 4
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20127
Ensembl gene	ENSG00000137634
Ensembl biotype	protein_coding
OMIM	618133
Entrez	54827

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000375478, ENST00000424261, ENST00000873916, ENST00000873917, ENST00000873918, ENST00000873919, ENST00000873920, ENST00000873921, ENST00000873922, ENST00000873923, ENST00000960740

RefSeq mRNA: 2 — MANE Select: NM_001077639 NM_001077639, NM_017678

CCDS: CCDS41718, CCDS44737

Canonical transcript exons

ENST00000375478 — 6 exons

Exon	Start	End
ENSE00000747506	114580132	114580338
ENSE00001125935	114595592	114595786
ENSE00001467206	114570591	114571473
ENSE00001467209	114582288	114583021
ENSE00003472427	114594664	114594769
ENSE00003616950	114581725	114581786

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 97.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4097 / max 171.0137, expressed in 14 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122374	0.1535	7
122372	0.1299	10
122375	0.1086	9
122373	0.0176	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	97.67	gold quality
colonic mucosa	UBERON:0000317	97.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.14	gold quality
mucosa of transverse colon	UBERON:0004991	97.05	gold quality
parotid gland	UBERON:0001831	95.31	gold quality
buccal mucosa cell	CL:0002336	91.63	gold quality
transverse colon	UBERON:0001157	88.00	gold quality
calcaneal tendon	UBERON:0003701	78.37	gold quality
colonic epithelium	UBERON:0000397	77.27	gold quality
vermiform appendix	UBERON:0001154	77.02	gold quality
large intestine	UBERON:0000059	76.10	gold quality
colon	UBERON:0001155	75.33	gold quality
caecum	UBERON:0001153	75.19	gold quality
ileal mucosa	UBERON:0000331	72.05	silver quality
intestine	UBERON:0000160	69.37	gold quality
tendon	UBERON:0000043	66.33	gold quality
epithelium of nasopharynx	UBERON:0001951	65.30	gold quality
saliva-secreting gland	UBERON:0001044	60.63	gold quality
tonsil	UBERON:0002372	59.75	gold quality
bone marrow cell	CL:0002092	59.70	silver quality
diaphragm	UBERON:0001103	59.70	gold quality
corpus epididymis	UBERON:0004359	59.08	gold quality
triceps brachii	UBERON:0001509	58.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	57.06	gold quality
gluteal muscle	UBERON:0002000	56.77	gold quality
prostate gland	UBERON:0002367	55.51	gold quality
nasal cavity epithelium	UBERON:0005384	55.18	gold quality
cardia of stomach	UBERON:0001162	54.54	gold quality
minor salivary gland	UBERON:0001830	51.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	51.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	50.47
E-ANND-3	yes	8.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting NXPE4, 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-4425	100.00	67.59	1049
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-496	98.66	69.80	931
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-449C-3P	97.75	67.86	462
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-411-5P	97.11	66.82	601
HSA-MIR-4714-5P	97.04	67.76	955
HSA-MIR-617	96.79	65.96	738
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-5591-3P	96.23	67.03	489
HSA-MIR-4259	95.68	65.25	582
HSA-MIR-1914-3P	95.07	63.37	762

Literature-anchored findings (GeneRIF, showing 1)

• Neurexophilin and PC-esterase domain family member 4 (NXPE4) and prostate androgen-regulated mucin-like protein 1 (PARM1) as prognostic biomarkers for colorectal cancer. (PMID:31297877)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nxpe4	ENSMUSG00000044229
rattus_norvegicus	Nxpe4	ENSRNOG00000070472

Paralogs (3): NXPE1 (ENSG00000095110), NXPE3 (ENSG00000144815), NXPE2 (ENSG00000204361)

Protein

Protein identifiers

NXPE family member 4 — Q6UWF7 (reviewed: Q6UWF7)

Alternative names: Protein FAM55D

All UniProt accessions (1): Q6UWF7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the NXPE family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWF7-1	1	yes
Q6UWF7-2	2

RefSeq proteins (2): NP_001071107, NP_060148 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR026845	NXPH/NXPE	Family
IPR057106	NXPE4_C	Domain

Pfam: PF06312, PF24536

UniProt features (13 total): glycosylation site 7, sequence variant 2, signal peptide 1, chain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWF7-F1	90.72	0.83

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 (7): 29, 38, 47, 48, 92, 160, 210

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, BROWN_MYELOID_CELL_DEVELOPMENT_UP, MODULE_48, MODULE_95, XU_GH1_EXOGENOUS_TARGETS_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, CHYLA_CBFA2T3_TARGETS_DN, MODULE_163, DLX2_TARGET_GENES, MIR519E_5P, MIR515_5P, MIR519D_5P, GSE10325_MYELOID_VS_LUPUS_MYELOID_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXPE4	SAMD13	Q5VXD3	506
NXPE4	REP15	Q6BDI9	479
NXPE4	ZNF726	A6NNF4	402
NXPE4	ADPRM	Q3LIE5	399
NXPE4	CCDC154	A6NI56	395
NXPE4	C11orf71	Q6IPW1	394
NXPE4	ZNF700	Q9H0M5	371
NXPE4	C6orf136	Q5SQH8	349
NXPE4	OVCA2	Q8WZ82	318
NXPE4	CEACAM7	Q14002	317
NXPE4	CWH43	Q9H720	311
NXPE4	ZNF768	Q9H5H4	310
NXPE4	CHST5	Q9GZS9	307
NXPE4	PCED1B	Q96HM7	303
NXPE4	SPINK4	O60575	283

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730

BioGRID (5): NXPE4 (Biochemical Activity), NXPE4 (Affinity Capture-MS), NXPE4 (Cross-Linking-MS (XL-MS)), NXPE4 (Cross-Linking-MS (XL-MS)), NXPE4 (Affinity Capture-MS)

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

833 predictions. Top by Δscore:

Variant	Effect	Δscore
11:114584573:C:CT	acceptor_gain	0.9900
11:114584574:A:T	acceptor_gain	0.9900
11:114584581:T:TC	acceptor_gain	0.9900
11:114571495:C:T	acceptor_gain	0.9800
11:114580130:A:AC	donor_gain	0.9700
11:114580131:C:CC	donor_gain	0.9700
11:114584581:T:C	acceptor_gain	0.9600
11:114571495:C:CT	acceptor_gain	0.9500
11:114584573:C:T	acceptor_gain	0.9500
11:114595586:TCATA:T	donor_loss	0.9500
11:114595588:ATACC:A	donor_loss	0.9500
11:114581656:A:T	acceptor_gain	0.9200
11:114581723:A:AC	donor_gain	0.9200
11:114581724:C:CC	donor_gain	0.9200
11:114582982:A:T	acceptor_gain	0.8900
11:114584580:A:C	acceptor_gain	0.8900
11:114584379:TCC:T	donor_gain	0.8800
11:114584380:C:CT	donor_gain	0.8800
11:114595592:C:A	donor_loss	0.8600
11:114581636:C:CC	acceptor_gain	0.8400
11:114583018:AAACC:A	acceptor_loss	0.8400
11:114583020:ACCTG:A	acceptor_loss	0.8400
11:114583021:CCTG:C	acceptor_loss	0.8400
11:114583022:C:A	acceptor_loss	0.8400
11:114583023:T:A	acceptor_loss	0.8400
11:114571496:A:T	acceptor_gain	0.8200
11:114583024:G:C	acceptor_loss	0.8100
11:114580140:CTGG:C	donor_gain	0.8000
11:114584381:C:CT	donor_gain	0.8000
11:114584587:C:CT	acceptor_gain	0.7900

AlphaMissense

3620 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:114582818:G:C	S100R	0.975
11:114582818:G:T	S100R	0.975
11:114582820:T:G	S100R	0.975
11:114582605:C:A	W171C	0.960
11:114582605:C:G	W171C	0.960
11:114582725:C:A	K131N	0.950
11:114582725:C:G	K131N	0.950
11:114582494:A:C	F208L	0.949
11:114582494:A:T	F208L	0.949
11:114582496:A:G	F208L	0.949
11:114582395:G:C	F241L	0.934
11:114582395:G:T	F241L	0.934
11:114582397:A:G	F241L	0.934
11:114582607:A:G	W171R	0.922
11:114582607:A:T	W171R	0.922
11:114582667:C:G	A151P	0.922
11:114582712:C:G	D136H	0.917
11:114582617:G:C	F167L	0.916
11:114582617:G:T	F167L	0.916
11:114582619:A:G	F167L	0.916
11:114582624:A:T	V165D	0.915
11:114582631:A:C	Y163D	0.908
11:114582673:C:G	A149P	0.906
11:114582699:G:T	A140D	0.903
11:114582710:A:C	D136E	0.900
11:114582710:A:T	D136E	0.900
11:114582636:C:A	G161V	0.897
11:114582711:T:G	D136A	0.895
11:114582506:G:C	F204L	0.894
11:114582506:G:T	F204L	0.894

dbSNP variants (sampled 300 via entrez): RS1000009320 (11:114613093 T>C), RS1000079857 (11:114632040 TATATA>T), RS1000091187 (11:114659516 C>T), RS1000121884 (11:114573969 A>G), RS1000145996 (11:114612859 A>C,G,T), RS1000198194 (11:114592189 A>C), RS1000264479 (11:114599254 T>A), RS1000274975 (11:114628870 A>G), RS1000313633 (11:114661181 T>C), RS1000372646 (11:114603242 C>G,T), RS1000388872 (11:114586399 C>G,T), RS1000461288 (11:114590472 T>G), RS1000472539 (11:114636768 T>C,G), RS1000502133 (11:114586508 A>G), RS1000507463 (11:114639340 G>A,C)

Disease associations

OMIM: gene MIM:618133 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001728_5	Ulcerative colitis	5.000000e-17
GCST004131_119	Inflammatory bowel disease	2.000000e-06
GCST004133_61	Ulcerative colitis	2.000000e-09
GCST009391_1364	Metabolite levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010366	lysophosphatidylethanolamine 16:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	affects binding, increases activity, increases expression	1
Acetaminophen	decreases expression	1
Ivermectin	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1

Clinical trials (associated diseases)

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