NXPE2

Summary

NXPE2 (neurexophilin and PC-esterase domain family member 2, HGNC:26331) is a protein-coding gene on chromosome 11q23.2, encoding NXPE family member 2 (Q96DL1).

Predicted to be located in membrane.

Source: NCBI Gene 120406 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 173 total
• MANE Select transcript: NM_182495

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26331
Approved symbol	NXPE2
Name	neurexophilin and PC-esterase domain family member 2
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25224
Ensembl gene	ENSG00000204361
Ensembl biotype	protein_coding
Entrez	120406

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000389586

RefSeq mRNA: 1 — MANE Select: NM_182495 NM_182495

CCDS: CCDS44738

Canonical transcript exons

ENST00000389586 — 6 exons

Exon	Start	End
ENSE00001467201	114698045	114698778
ENSE00001467203	114679657	114679762
ENSE00001506299	114706395	114707069
ENSE00001506300	114705781	114705996
ENSE00001506301	114703991	114704052
ENSE00002321280	114678527	114678601

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 79.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1573 / max 66.9184, expressed in 19 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116822	0.0961	18
116820	0.0307	11
116821	0.0305	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	79.64	gold quality
rectum	UBERON:0001052	79.46	gold quality
colonic epithelium	UBERON:0000397	71.74	gold quality
mucosa of transverse colon	UBERON:0004991	71.05	gold quality
transverse colon	UBERON:0001157	67.47	gold quality
saliva-secreting gland	UBERON:0001044	61.78	gold quality
smooth muscle tissue	UBERON:0001135	61.38	gold quality
minor salivary gland	UBERON:0001830	59.51	gold quality
vermiform appendix	UBERON:0001154	59.43	gold quality
ventricular zone	UBERON:0003053	58.46	gold quality
duodenum	UBERON:0002114	58.22	gold quality
tonsil	UBERON:0002372	57.90	gold quality
colon	UBERON:0001155	57.36	gold quality
intestine	UBERON:0000160	56.15	gold quality
small intestine	UBERON:0002108	52.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	51.35	gold quality
endometrium	UBERON:0001295	50.24	gold quality
stromal cell of endometrium	CL:0002255	48.60	gold quality
muscle tissue	UBERON:0002385	45.25	gold quality
gall bladder	UBERON:0002110	45.21	gold quality
ganglionic eminence	UBERON:0004023	44.47	silver quality
muscle layer of sigmoid colon	UBERON:0035805	43.02	gold quality
tibial artery	UBERON:0007610	42.72	gold quality
popliteal artery	UBERON:0002250	42.70	gold quality
islet of Langerhans	UBERON:0000006	42.62	gold quality
skeletal muscle tissue	UBERON:0001134	41.48	gold quality
cortical plate	UBERON:0005343	40.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	40.14	gold quality
prefrontal cortex	UBERON:0000451	40.02	gold quality
myometrium	UBERON:0001296	39.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.58

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nxpe2	ENSMUSG00000032028
rattus_norvegicus	Nxpe2	ENSRNOG00000027847

Paralogs (3): NXPE1 (ENSG00000095110), NXPE4 (ENSG00000137634), NXPE3 (ENSG00000144815)

Protein

Protein identifiers

NXPE family member 2 — Q96DL1 (reviewed: Q96DL1)

Alternative names: Protein FAM55B

All UniProt accessions (1): Q96DL1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Miscellaneous. Gene prediction based on EST data and similarity to mouse ortholog.

Similarity. Belongs to the NXPE family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96DL1-1	1	yes
Q96DL1-3	2

RefSeq proteins (1): NP_872301* (*=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 (5 total): splice variant 2, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DL1-F1	89.77	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, VANLOO_SP3_TARGETS_DN, PEDRIOLI_MIR31_TARGETS_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_BALBC_MOUSE_DN, DLX6_TARGET_GENES, MSX1_TARGET_GENES, GSE14308_TH17_VS_NATURAL_TREG_DN, DESCARTES_MAIN_FETAL_LENS_FIBRE_CELLS, LHX2_TARGET_GENES, GSE39820_IL1B_IL6_VS_IL1B_IL6_IL23A_TREATED_CD4_TCELL_UP, GSE369_PRE_VS_POST_IL6_INJECTION_IFNG_KO_LIVER_UP, GSE19888_ADENOSINE_A3R_INH_VS_INH_PRETREAT_AND_ACT_WITH_TCELL_MEMBRANES_MAST_CELL_DN, GSE21774_CD56_BRIGHT_VS_DIM_CD62L_POSITIVE_NK_CELL_UP, GSE21774_CD56_BRIGHT_VS_DIM_CD62L_POSITIVE_NK_CELL_DN, GSE21546_SAP1A_KO_VS_SAP1A_KO_AND_ELK1_KO_ANTI_CD3_STIM_DP_THYMOCYTES_UP

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXPE2	MMD	Q15546	504
NXPE2	STARD13	Q9Y3M8	418
NXPE2	LHFPL1	Q86WI0	400
NXPE2	C11orf71	Q6IPW1	398
NXPE2	TMEM132E	Q6IEE7	387
NXPE2	FRMPD3	Q5JV73	379
NXPE2	ZNFX1	Q9P2E3	371
NXPE2	HHIPL2	Q6UWX4	360
NXPE2	HEMGN	Q9BXL5	355
NXPE2	TXNDC15	Q96J42	351
NXPE2	SPTB	P11277	348
NXPE2	ASB11	Q8WXH4	343
NXPE2	MROH2B	Q7Z745	339
NXPE2	OR2H2	O95918	320
NXPE2	IGSF9B	Q9UPX0	314

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SCRIB	NXPE2	psi-mi:“MI:0915”(physical association)	0.400
NXPE2	DLG1	psi-mi:“MI:0915”(physical association)	0.400
ERBIN	NXPE2	psi-mi:“MI:0915”(physical association)	0.400
NXPE2	PGAP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): NXPE2 (Two-hybrid), NXPE2 (Two-hybrid), PGAP1 (Affinity Capture-MS), HELLS (Affinity Capture-MS), FAM213A (Affinity Capture-MS), MAVS (Affinity Capture-MS), LMF1 (Affinity Capture-MS), ARL8B (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	156
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

689 predictions. Top by Δscore:

Variant	Effect	Δscore
11:114698035:A:AG	acceptor_gain	1.0000
11:114698036:A:G	acceptor_gain	1.0000
11:114698043:A:AG	acceptor_gain	1.0000
11:114698044:G:GG	acceptor_gain	1.0000
11:114703987:GCAG:G	acceptor_loss	1.0000
11:114703988:CAGGT:C	acceptor_loss	1.0000
11:114703989:A:T	acceptor_loss	1.0000
11:114704053:G:GG	donor_gain	1.0000
11:114698038:A:AG	acceptor_gain	0.9900
11:114698040:TTCAG:T	acceptor_loss	0.9900
11:114698041:TCAG:T	acceptor_loss	0.9900
11:114698042:CAGTT:C	acceptor_loss	0.9900
11:114698043:A:AC	acceptor_loss	0.9900
11:114698044:GT:G	acceptor_gain	0.9900
11:114698044:GTT:G	acceptor_gain	0.9900
11:114698044:GTTC:G	acceptor_gain	0.9900
11:114698044:GTTCT:G	acceptor_gain	0.9900
11:114703989:A:AG	acceptor_gain	0.9900
11:114703990:G:GG	acceptor_gain	0.9900
11:114704048:CAACA:C	donor_gain	0.9900
11:114704049:AACAG:A	donor_loss	0.9900
11:114704050:ACA:A	donor_gain	0.9900
11:114704051:CA:C	donor_gain	0.9900
11:114704051:CAGTA:C	donor_loss	0.9900
11:114704052:AGTAA:A	donor_loss	0.9900
11:114704053:GT:G	donor_loss	0.9900
11:114704054:T:A	donor_loss	0.9900
11:114704055:A:AG	donor_loss	0.9900
11:114705780:GA:G	acceptor_gain	0.9900
11:114705780:GAGA:G	acceptor_gain	0.9900

AlphaMissense

3766 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:114698246:A:C	S112R	0.981
11:114698248:C:A	S112R	0.981
11:114698248:C:G	S112R	0.981
11:114698570:T:C	F220L	0.965
11:114698572:T:A	F220L	0.965
11:114698572:T:G	F220L	0.965
11:114698341:G:C	K143N	0.956
11:114698341:G:T	K143N	0.956
11:114698669:T:C	F253L	0.947
11:114698671:C:A	F253L	0.947
11:114698671:C:G	F253L	0.947
11:114706714:A:C	K488N	0.945
11:114706714:A:T	K488N	0.945
11:114705966:T:A	W372R	0.939
11:114705966:T:C	W372R	0.939
11:114698558:T:C	F216L	0.936
11:114698560:C:A	F216L	0.936
11:114698560:C:G	F216L	0.936
11:114706757:A:C	S503R	0.934
11:114706759:T:A	S503R	0.934
11:114706759:T:G	S503R	0.934
11:114706619:T:C	F457L	0.930
11:114706621:T:A	F457L	0.930
11:114706621:T:G	F457L	0.930
11:114705858:T:A	W336R	0.922
11:114705858:T:C	W336R	0.922
11:114698354:G:C	D148H	0.918
11:114698447:T:C	F179L	0.917
11:114698449:C:A	F179L	0.917
11:114698449:C:G	F179L	0.917

dbSNP variants (sampled 300 via entrez): RS1000009320 (11:114613093 T>C), RS1000013203 (11:114487352 C>G), RS1000063196 (11:114804189 A>T), RS1000070174 (11:114515176 C>T), RS1000070672 (11:114488506 G>A,C), RS1000079857 (11:114632040 TATATA>T), RS1000091187 (11:114659516 C>T), RS1000121884 (11:114573969 A>G), RS1000130618 (11:114742249 G>A,T), RS1000145996 (11:114612859 A>C,G,T), RS1000160062 (11:114708085 G>A,T), RS1000161844 (11:114559299 C>T), RS1000171967 (11:114510130 A>C), RS1000187193 (11:114505926 G>A), RS1000192169 (11:114696778 G>A)

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

7 associations (top):

Study	Trait	p-value
GCST000105_1	Urinary albumin excretion	2.000000e-06
GCST004495_37	BMI (adjusted for smoking behaviour)	4.000000e-08
GCST004497_136	Body mass index (joint analysis main effects and smoking interaction)	4.000000e-08
GCST004499_33	BMI in non-smokers	3.000000e-08
GCST007576_392	Chronotype	6.000000e-08
GCST008161_11	Waist circumference adjusted for body mass index	5.000000e-06
GCST011038_8	Parkinson’s disease progression (motor)	7.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004285	albuminuria
EFO:0004318	smoking behavior
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Cadmium	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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