NRSN2

Summary

NRSN2 (neurensin 2, HGNC:16229) is a protein-coding gene on chromosome 20p13, encoding Neurensin-2 (Q9GZP1). May play a role in maintenance and/or transport of vesicles.

Predicted to be involved in nervous system development. Located in plasma membrane.

Source: NCBI Gene 80023 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001323682

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16229
Approved symbol	NRSN2
Name	neurensin 2
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	dJ1103G7.6
Ensembl gene	ENSG00000125841
Ensembl biotype	protein_coding
OMIM	610666
Entrez	80023

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 33 protein_coding

ENST00000382285, ENST00000382291, ENST00000470439, ENST00000492242, ENST00000608467, ENST00000608736, ENST00000608875, ENST00000609179, ENST00000609504, ENST00000714400, ENST00000714401, ENST00000714402, ENST00000714403, ENST00000714404, ENST00000890616, ENST00000890617, ENST00000890618, ENST00000890619, ENST00000890620, ENST00000890621, ENST00000890622, ENST00000890623, ENST00000890624, ENST00000890625, ENST00000890626, ENST00000914904, ENST00000914905, ENST00000914906, ENST00000914907, ENST00000914908, ENST00000970935, ENST00000970936, ENST00000970937

RefSeq mRNA: 8 — MANE Select: NM_001323682 NM_001323679, NM_001323680, NM_001323681, NM_001323682, NM_001323683, NM_001323684, NM_001323685, NM_024958

CCDS: CCDS12996

Canonical transcript exons

ENST00000382285 — 5 exons

Exon	Start	End
ENSE00001491551	353210	354862
ENSE00001491552	347434	347512
ENSE00001491647	349249	349363
ENSE00003710328	349638	349832
ENSE00004023857	347111	347142

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 98.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.4538 / max 223.8310, expressed in 1638 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183020	18.2432	1613
183019	1.0065	496
183017	0.8264	581
183018	0.6963	479
183022	0.4727	268
183023	0.1922	73
183021	0.0165	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.11	gold quality
anterior cingulate cortex	UBERON:0009835	97.59	gold quality
cingulate cortex	UBERON:0003027	97.51	gold quality
prefrontal cortex	UBERON:0000451	96.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.92	gold quality
cerebellar hemisphere	UBERON:0002245	95.75	gold quality
cerebellar cortex	UBERON:0002129	95.66	gold quality
adenohypophysis	UBERON:0002196	95.66	gold quality
caudate nucleus	UBERON:0001873	95.38	gold quality
left adrenal gland	UBERON:0001234	94.60	gold quality
left adrenal gland cortex	UBERON:0035825	94.60	gold quality
right adrenal gland	UBERON:0001233	94.56	gold quality
amygdala	UBERON:0001876	94.50	gold quality
nucleus accumbens	UBERON:0001882	94.45	gold quality
frontal cortex	UBERON:0001870	94.29	gold quality
right adrenal gland cortex	UBERON:0035827	94.21	gold quality
neocortex	UBERON:0001950	94.19	gold quality
cortical plate	UBERON:0005343	94.07	gold quality
cerebellum	UBERON:0002037	93.39	gold quality
stromal cell of endometrium	CL:0002255	93.33	gold quality
pituitary gland	UBERON:0000007	93.05	gold quality
putamen	UBERON:0001874	92.73	gold quality
apex of heart	UBERON:0002098	92.73	gold quality
cerebral cortex	UBERON:0000956	92.43	gold quality
hypothalamus	UBERON:0001898	92.42	gold quality
right ovary	UBERON:0002118	92.02	gold quality
adrenal cortex	UBERON:0001235	92.00	gold quality
adrenal gland	UBERON:0002369	92.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	6.68
E-ANND-3	yes	5.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting NRSN2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3127-3P	98.94	67.34	1055

Literature-anchored findings (GeneRIF, showing 8)

• NRSN2 could be a tumor suppressor gene for hepatocellular carcinoma and a candidate biomarker for long-term survival in HCC (PMID:19824122)
• SOX12 and NRSN2 were identified as candidate genes that may be involved in the developmental defects in 20p13 microdeletion. (PMID:24019301)
• our findings suggest that NRSN2 promotes non-small cell lung cancer cell growth through PI3K/Akt/mTOR pathway (PMID:26045763)
• Down regulated NRSN2 promotes cell proliferation and cell survival in hepatocellular liver cancer. (PMID:26055238)
• NRSN2 could promote ovarian cancer cell proliferation, invasion and chemoresistance in ovarian adenocarcinoma. (PMID:27908706)
• E2F1-activated NRSN2 promotes esophageal squamous cell carcinoma progression through AKT/mTOR pathway. (PMID:35662041)
• miR-488-3p Represses Malignant Behaviors and Facilitates Autophagy of Osteosarcoma Cells by Targeting Neurensin-2. (PMID:37365792)
• LncRNA LUESCC promotes esophageal squamous cell carcinoma by targeting the miR-6785-5p/NRSN2 axis. (PMID:38457049)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nrsn2	ENSMUSG00000059361

Paralogs (1): NRSN1 (ENSG00000152954)

Protein

Protein identifiers

Neurensin-2 — Q9GZP1 (reviewed: Q9GZP1)

All UniProt accessions (9): Q9GZP1, A0A087WVS5, A0AAQ5BI16, A0AAQ5BI19, V9GY99, V9GYN1, V9GYV8, V9GYY0, V9GZ28

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in maintenance and/or transport of vesicles.

Subcellular location. Membrane.

Similarity. Belongs to the VMP family.

RefSeq proteins (8): NP_001310608, NP_001310609, NP_001310610, NP_001310611, NP_001310612, NP_001310613, NP_001310614, NP_079234 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024883	Neurensin	Family

Pfam: PF14927

UniProt features (8 total): sequence variant 3, transmembrane region 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZP1-F1	63.97	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): RORA1_01, TGACCTY_ERR1_Q2, AACTTT_UNKNOWN, GOCC_NEURON_PROJECTION, RFX1_02, TGACCTTG_SF1_Q6, GOCC_CELL_BODY, GOCC_SOMATODENDRITIC_COMPARTMENT, BLALOCK_ALZHEIMERS_DISEASE_DN, ER_Q6_02, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, MIKKELSEN_ES_ICP_WITH_H3K4ME3, KRIEG_HYPOXIA_NOT_VIA_KDM3A, CAMP_UP.V1_UP, OISHI_CHOLANGIOMA_STEM_CELL_LIKE_UP

GO Biological Process (1): nervous system development (GO:0007399)

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

GO Cellular Component (6): plasma membrane (GO:0005886), transport vesicle (GO:0030133), neuron projection (GO:0043005), neuronal cell body (GO:0043025), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
binding	1
membrane	1
cell periphery	1
endomembrane system	1
cytoplasmic vesicle	1
plasma membrane bounded cell projection	1
somatodendritic compartment	1
cell body	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRSN2	SOX12	O15370	528
NRSN2	ZBBX	A8MT70	519
NRSN2	GJD4	Q96KN9	480
NRSN2	SOX15	P35717	478
NRSN2	HMGXB3	Q12766	478
NRSN2	NXPH4	O95158	462
NRSN2	CLCC1	Q96S66	462
NRSN2	FSTL5	Q8N475	431
NRSN2	ASPDH	A6ND91	429
NRSN2	FAM174A	Q8TBP5	422
NRSN2	TRIB3	Q96RU7	421
NRSN2	CNTN4	Q8IWV2	418
NRSN2	SNCB	Q16143	413
NRSN2	DPP10	Q8N608	410
NRSN2	IL17REL	Q6ZVW7	408

IntAct

24 interactions, top by confidence:

A	B	Type	Score
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
SGTA	NRSN2	psi-mi:“MI:0915”(physical association)	0.560
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
NRSN2	ZDHHC17	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TSPAN10	KLRG2	psi-mi:“MI:0914”(association)	0.350
TACSTD2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
RNF149	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PDGFRB	HIP1R	psi-mi:“MI:0914”(association)	0.350
NRSN2	MZT2B	psi-mi:“MI:0914”(association)	0.350
SLC4A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SGTA	NRSN2	psi-mi:“MI:0915”(physical association)	0.000
ANKZF1	NRSN2	psi-mi:“MI:0915”(physical association)	0.000
GOLM1	NRSN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): NRSN2 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS), FITM2 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS), NRSN2 (Two-hybrid), NRSN2 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS), FITM2 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS), NRSN2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: P97799, Q5HZK2, Q8IZ57, Q9GZP1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

780 predictions. Top by Δscore:

Variant	Effect	Δscore
20:347140:GAG:G	donor_gain	1.0000
20:347140:GAGG:G	donor_loss	1.0000
20:347141:AGGT:A	donor_loss	1.0000
20:353205:CCTA:C	acceptor_loss	1.0000
20:353206:CTA:C	acceptor_loss	1.0000
20:353208:A:AG	acceptor_gain	1.0000
20:353209:G:GC	acceptor_loss	1.0000
20:353209:G:GG	acceptor_gain	1.0000
20:353209:GATCA:G	acceptor_gain	1.0000
20:347138:GAGAG:G	donor_gain	0.9900
20:347143:G:GG	donor_gain	0.9900
20:347144:T:G	donor_loss	0.9900
20:349636:AGG:A	acceptor_gain	0.9900
20:349637:GGG:G	acceptor_gain	0.9900
20:349833:G:C	donor_loss	0.9900
20:349834:T:A	donor_loss	0.9900
20:353209:GA:G	acceptor_gain	0.9900
20:353209:GATC:G	acceptor_gain	0.9900
20:347493:G:GT	donor_gain	0.9800
20:349828:GGAAG:G	donor_gain	0.9800
20:349829:GAAG:G	donor_gain	0.9800
20:349829:GAAGG:G	donor_gain	0.9800
20:349833:G:GG	donor_gain	0.9800
20:353209:GAT:G	acceptor_gain	0.9800
20:349830:A:T	donor_gain	0.9700
20:353197:T:TA	acceptor_gain	0.9700
20:347999:GAC:G	donor_gain	0.9600
20:349615:GCT:G	acceptor_gain	0.9600
20:349636:AG:A	acceptor_gain	0.9600
20:349637:GG:G	acceptor_gain	0.9600

AlphaMissense

1310 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:349737:T:C	F32L	0.987
20:349739:C:A	F32L	0.987
20:349739:C:G	F32L	0.987
20:353246:G:C	G76R	0.981
20:353247:G:A	G76D	0.980
20:353376:G:A	G119D	0.978
20:353268:G:A	G83D	0.972
20:353347:C:A	N109K	0.968
20:353347:C:G	N109K	0.968
20:353375:G:C	G119R	0.967
20:353213:A:C	S65R	0.966
20:353215:C:A	S65R	0.966
20:353215:C:G	S65R	0.966
20:349738:T:G	F32C	0.964
20:353256:C:A	A79D	0.963
20:353225:G:A	G69R	0.962
20:353225:G:C	G69R	0.962
20:353267:G:C	G83R	0.962
20:353387:T:C	C123R	0.958
20:353375:G:T	G119C	0.956
20:353226:G:A	G69E	0.955
20:349723:C:T	S27F	0.951
20:349738:T:C	F32S	0.948
20:353253:C:A	A78E	0.947
20:353346:A:T	N109I	0.944
20:353255:G:C	A79P	0.943
20:353417:T:C	C133R	0.942
20:353259:T:C	L80P	0.940
20:353287:G:C	K89N	0.939
20:353287:G:T	K89N	0.939

dbSNP variants (sampled 300 via entrez): RS1000119801 (20:355342 T>A), RS1000332962 (20:349455 C>T), RS1000416098 (20:351770 C>A,G), RS1000680368 (20:346083 T>C), RS1000709181 (20:349054 A>G), RS1001067846 (20:359937 T>C), RS1001204926 (20:355629 A>C), RS1001434720 (20:358616 G>A,T), RS1001549 (20:354581 G>A,T), RS1001573232 (20:352988 G>A,C), RS1001742743 (20:348111 A>T), RS1002126251 (20:352571 C>T), RS1002240748 (20:352870 G>A), RS1002315603 (20:354210 T>C), RS1002364024 (20:347944 G>A)

Disease associations

OMIM: gene MIM:610666 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007010_4	Logical memory (delayed recall)	6.000000e-07
GCST007011_4	Logical memory (immediate recall)	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	2
Arsenic	increases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
abrine	decreases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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