NRSN1

Summary

NRSN1 (neurensin 1, HGNC:17881) is a protein-coding gene on chromosome 6p22.3, encoding Neurensin-1 (Q8IZ57). May play an important role in neural organelle transport, and in transduction of nerve signals or in nerve growth.

Predicted to be involved in nervous system development. Predicted to be located in cytoplasmic vesicle and growth cone. Predicted to be active in neuron projection; neuronal cell body; and transport vesicle.

Source: NCBI Gene 140767 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_080723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17881
Approved symbol	NRSN1
Name	neurensin 1
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	p24
Ensembl gene	ENSG00000152954
Ensembl biotype	protein_coding
OMIM	616630
Entrez	140767

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000378475, ENST00000378477, ENST00000378478, ENST00000378491, ENST00000463207, ENST00000468195, ENST00000475830, ENST00000892078, ENST00000892079, ENST00000892080, ENST00000944487, ENST00000944488

RefSeq mRNA: 1 — MANE Select: NM_080723 NM_080723

CCDS: CCDS4549

Canonical transcript exons

ENST00000378491 — 4 exons

Exon	Start	End
ENSE00001085328	24128128	24128200
ENSE00001282051	24126215	24126340
ENSE00001477714	24145548	24147530
ENSE00003650908	24134319	24134516

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 96.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.9235 / max 473.6693, expressed in 162 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66378	6.9235	162

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsolateral prefrontal cortex	UBERON:0009834	96.76	gold quality
anterior cingulate cortex	UBERON:0009835	96.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.19	gold quality
prefrontal cortex	UBERON:0000451	96.07	gold quality
nucleus accumbens	UBERON:0001882	95.85	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.58	gold quality
right frontal lobe	UBERON:0002810	95.52	gold quality
frontal cortex	UBERON:0001870	95.48	gold quality
hypothalamus	UBERON:0001898	95.30	gold quality
neocortex	UBERON:0001950	95.09	gold quality
amygdala	UBERON:0001876	94.97	gold quality
superior frontal gyrus	UBERON:0002661	94.68	gold quality
putamen	UBERON:0001874	94.55	gold quality
caudate nucleus	UBERON:0001873	94.33	gold quality
middle temporal gyrus	UBERON:0002771	93.84	gold quality
cerebral cortex	UBERON:0000956	93.74	gold quality
forebrain	UBERON:0001890	93.64	gold quality
temporal lobe	UBERON:0001871	93.53	gold quality
pituitary gland	UBERON:0000007	93.04	gold quality
postcentral gyrus	UBERON:0002581	92.77	gold quality
entorhinal cortex	UBERON:0002728	92.22	gold quality
parietal lobe	UBERON:0001872	91.94	gold quality
pons	UBERON:0000988	91.82	gold quality
brain	UBERON:0000955	91.80	gold quality
primary visual cortex	UBERON:0002436	91.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.75	gold quality
adenohypophysis	UBERON:0002196	91.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.54	gold quality
cortical plate	UBERON:0005343	91.44	gold quality
occipital lobe	UBERON:0002021	90.21	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	1363.40
E-MTAB-3929	yes	348.13
E-ANND-3	yes	4.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting NRSN1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606

Literature-anchored findings (GeneRIF, showing 5)

• Cloning, expression and characterization of VMP gene. (PMID:12463420)
• dilysine retrieval signal-containing p24 proteins, p24alpha(2) and p24delta(1), bind with gamma-secretase complexes and collaborate in attenuating gamma-cleavage of beta-amyloid precursor protein (PMID:20807314)
• GAL, GAP43 and NRSN1 single nucleotide polymorphisms and related gene-gene interaction networks might be involved in the altered susceptibility to Hirschsprung disease in the Han Chinese population. (PMID:29654647)
• Neuregulin-1 promotes mitochondrial biogenesis, attenuates mitochondrial dysfunction, and prevents hypoxia/reoxygenation injury in neonatal cardiomyocytes. (PMID:32037595)
• Developmental dyslexia susceptibility genes DNAAF4, DCDC2, and NRSN1 are associated with brain function in fluently reading adolescents and young adults. (PMID:38610086)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrsn1l	ENSDARG00000056572
danio_rerio	nrsn1	ENSDARG00000111235
mus_musculus	Nrsn1	ENSMUSG00000048978
rattus_norvegicus	Nrsn1	ENSRNOG00000017444

Paralogs (1): NRSN2 (ENSG00000125841)

Protein

Protein identifiers

Neurensin-1 — Q8IZ57 (reviewed: Q8IZ57)

Alternative names: Neuro-p24, Vesicular membrane protein of 24 kDa

All UniProt accessions (3): Q8IZ57, Q5VTS0, Q5VTS2

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in neural organelle transport, and in transduction of nerve signals or in nerve growth. May play a role in neurite extension. May play a role in memory consolidation.

Subcellular location. Membrane. Cell projection. Neuron projection.

Tissue specificity. Expressed in brain. Not detectable in other tissues tested.

Similarity. Belongs to the VMP family.

RefSeq proteins (1): NP_542454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024883	Neurensin	Family

Pfam: PF14927

UniProt features (7 total): transmembrane region 2, sequence variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZ57-F1	69.20	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, BRN2_01, AACTTT_UNKNOWN, GOCC_NEURON_PROJECTION, GCM_MAPK10, CREBP1_01, LEE_TARGETS_OF_PTCH1_AND_SUFU_DN, NRSF_01, GOCC_CELL_BODY

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

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

GO Cellular Component (7): membrane (GO:0016020), transport vesicle (GO:0030133), growth cone (GO:0030426), cytoplasmic vesicle (GO:0031410), neuron projection (GO:0043005), neuronal cell body (GO:0043025), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
system development	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
site of polarized growth	1
distal axon	1
cytoplasm	1
intracellular vesicle	1
plasma membrane bounded cell projection	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRSN1	ARHGAP9	Q9BRR9	630
NRSN1	KIAA0319	Q5VV43	582
NRSN1	DCDC2	Q9UHG0	576
NRSN1	CAMK2N1	Q7Z7J9	541
NRSN1	MAPK13	O15264	488
NRSN1	SRRM4	A7MD48	469
NRSN1	KCNH4	Q9UQ05	436
NRSN1	KAAG1	Q9UBP8	435
NRSN1	NGEF	Q8N5V2	424
NRSN1	DNAAF4	Q8WXU2	424
NRSN1	HCRTR1	O43613	421
NRSN1	MAP6D1	Q9H9H5	400
NRSN1	C6orf62	Q9GZU0	399
NRSN1	ACOT13	Q9NPJ3	392
NRSN1	MRS2	Q9HD23	385

IntAct

24 interactions, top by confidence:

A	B	Type	Score
FATE1	NRSN1	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	RNF24	psi-mi:“MI:0915”(physical association)	0.560
FCGR1A	NRSN1	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	GPA33	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	LYVE1	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
NRSN1	IGLC7	psi-mi:“MI:0914”(association)	0.350
NRSN1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.000
NRSN1	SPACA1	psi-mi:“MI:0915”(physical association)	0.000
NRSN1	RNF24	psi-mi:“MI:0915”(physical association)	0.000
NRSN1	FCGR1A	psi-mi:“MI:0915”(physical association)	0.000
NRSN1	GPA33	psi-mi:“MI:0915”(physical association)	0.000
NRSN1	LYVE1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (177): NRSN1 (Two-hybrid), NRSN1 (Two-hybrid), NRSN1 (Two-hybrid), NRSN1 (Two-hybrid), NRSN1 (Two-hybrid), NRSN1 (Two-hybrid), NRSN1 (Two-hybrid), EGFL7 (Affinity Capture-MS), RHBDD1 (Affinity Capture-MS), MET (Affinity Capture-MS), B4GALT6 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), PTPN23 (Affinity Capture-MS), LGR4 (Affinity Capture-MS), FUT8 (Affinity Capture-MS)

ESM2 similar proteins: A6NCQ9, D2H6Z0, D2H788, D3ZBM4, D4A723, E1C2W7, P97432, P97799, Q13145, Q14596, Q3SWY0, Q3T0Y9, Q3TXX3, Q501R9, Q5F479, Q5R7K2, Q5RC94, Q5RF77, Q5T4F4, Q60943, Q60953, Q68D51, Q68EV7, Q6GND7, Q6INB3, Q6P7B7, Q6P9P8, Q80ZD7, Q80ZD8, Q810L3, Q86WK6, Q8BG47, Q8BGE4, Q8C432, Q8CEF8, Q8HYZ0, Q8IZ57, Q8JZL1, Q8N6D2, Q8N8N0

Diamond homologs: P97799, Q5HZK2, Q8IZ57, Q9GZP1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

761 predictions. Top by Δscore:

Variant	Effect	Δscore
6:24126297:C:G	donor_gain	1.0000
6:24126337:GGGG:G	donor_gain	1.0000
6:24126338:GGGG:G	donor_gain	1.0000
6:24128196:CAAAG:C	donor_loss	1.0000
6:24128197:AAAGG:A	donor_loss	1.0000
6:24128198:AAGGT:A	donor_loss	1.0000
6:24128199:AGGTA:A	donor_loss	1.0000
6:24128200:GGT:G	donor_loss	1.0000
6:24128202:T:G	donor_loss	1.0000
6:24129408:G:GT	donor_gain	1.0000
6:24129412:TTTCA:T	donor_gain	1.0000
6:24126338:GGG:G	donor_gain	0.9900
6:24126339:GG:G	donor_gain	0.9900
6:24126339:GGG:G	donor_gain	0.9900
6:24126340:GG:G	donor_gain	0.9900
6:24126341:G:A	donor_loss	0.9900
6:24126342:TAG:T	donor_loss	0.9900
6:24128123:AATAG:A	acceptor_loss	0.9900
6:24128125:TAGG:T	acceptor_loss	0.9900
6:24128126:A:AG	acceptor_gain	0.9900
6:24128126:AG:A	acceptor_gain	0.9900
6:24128127:G:GG	acceptor_gain	0.9900
6:24128127:GG:G	acceptor_gain	0.9900
6:24127096:A:T	donor_gain	0.9800
6:24128127:GGATT:G	acceptor_gain	0.9800
6:24128201:G:GG	donor_gain	0.9800
6:24129419:G:GG	donor_gain	0.9800
6:24134317:AGCTG:A	acceptor_gain	0.9800
6:24134318:GCT:G	acceptor_gain	0.9800
6:24134318:GCTGG:G	acceptor_gain	0.9800

AlphaMissense

1263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:24134424:T:C	F33L	0.994
6:24134426:T:A	F33L	0.994
6:24134426:T:G	F33L	0.994
6:24134425:T:C	F33S	0.980
6:24134425:T:G	F33C	0.977
6:24145728:T:C	C124R	0.975
6:24145735:G:A	G126E	0.974
6:24145584:G:A	G76R	0.972
6:24145584:G:C	G76R	0.972
6:24145585:G:A	G76E	0.967
6:24145563:G:C	G69R	0.965
6:24145714:G:A	G119E	0.965
6:24145564:G:A	G69D	0.962
6:24145737:G:C	G127R	0.960
6:24145713:G:A	G119R	0.957
6:24145713:G:C	G119R	0.957
6:24145734:G:A	G126R	0.955
6:24145734:G:C	G126R	0.955
6:24145738:G:A	G127D	0.954
6:24145755:T:C	C133R	0.953
6:24145685:C:A	N109K	0.942
6:24145685:C:G	N109K	0.942
6:24134404:T:A	V26D	0.941
6:24134401:G:A	G25E	0.935
6:24145605:G:C	G83R	0.935
6:24145606:G:A	G83D	0.930
6:24134407:G:C	R27P	0.927
6:24134416:T:C	L30P	0.924
6:24134404:T:C	V26A	0.920
6:24145716:G:C	A120P	0.920

dbSNP variants (sampled 300 via entrez): RS1000028123 (6:24137632 T>G), RS1000427877 (6:24124994 G>T), RS1000437205 (6:24135212 G>A), RS1000808923 (6:24128351 GT>G), RS1000846917 (6:24130599 C>A), RS1000973328 (6:24139524 G>A,C), RS1001048561 (6:24136563 C>T), RS1001415934 (6:24129929 G>C,T), RS1001502977 (6:24140450 T>C), RS1001614340 (6:24145982 T>A,C), RS1001640456 (6:24142476 G>A,T), RS1001817627 (6:24128522 C>G,T), RS1001923509 (6:24141453 T>TC), RS1002063541 (6:24146260 G>A,T), RS1002069858 (6:24146729 A>T)

Disease associations

OMIM: gene MIM:616630 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000905_3	Information processing speed	4.000000e-06
GCST002127_32	Periodontitis (Mean PAL)	4.000000e-06
GCST004750_77	Squamous cell lung carcinoma	3.000000e-06
GCST005023_34	Initial pursuit acceleration	5.000000e-08
GCST008114_27	Type 2 diabetes	2.000000e-06
GCST008438_3	Alzheimer’s disease in hypertension	1.000000e-06
GCST010479_73	Coronary artery disease	5.000000e-09
GCST90013406_201	Liver enzyme levels (alkaline phosphatase)	2.000000e-46

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004363	information processing speed
EFO:0008434	initial pursuit acceleration
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases expression	1
Acetaminophen	increases expression	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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