NRN1L

Summary

NRN1L (neuritin 1 like, HGNC:29811) is a protein-coding gene on chromosome 16q22.1, encoding Neuritin-like protein (Q496H8).

The protein encoded by this gene is extracellular and enhances both neurite growth and neuronal survival. The encoded protein is found both as a GPI anchored membrane-bound form and as a secreted form. This activity-related ligand functions as a homodimer or heterodimer.

Source: NCBI Gene 123904 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_198443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29811
Approved symbol	NRN1L
Name	neuritin 1 like
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	UNQ2446, MRCC2446
Ensembl gene	ENSG00000188038
Ensembl biotype	protein_coding
Entrez	123904

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000339176, ENST00000576147, ENST00000576758

RefSeq mRNA: 2 — MANE Select: NM_198443 NM_001348682, NM_198443

CCDS: CCDS10850

Canonical transcript exons

ENST00000339176 — 3 exons

Exon	Start	End
ENSE00001382483	67885722	67885854
ENSE00001384007	67885974	67886368
ENSE00002659087	67884885	67884982

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 79.92.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4366 / max 257.7276, expressed in 258 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154691	1.4366	258

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.92	silver quality
putamen	UBERON:0001874	78.14	gold quality
adrenal tissue	UBERON:0018303	77.77	gold quality
caudate nucleus	UBERON:0001873	75.16	gold quality
nucleus accumbens	UBERON:0001882	74.93	gold quality
adenohypophysis	UBERON:0002196	74.49	gold quality
cerebellar hemisphere	UBERON:0002245	74.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.23	gold quality
cerebellar cortex	UBERON:0002129	74.08	gold quality
cerebellum	UBERON:0002037	73.98	gold quality
pituitary gland	UBERON:0000007	73.48	gold quality
hypothalamus	UBERON:0001898	72.83	gold quality
apex of heart	UBERON:0002098	70.50	gold quality
granulocyte	CL:0000094	70.36	gold quality
brain	UBERON:0000955	69.65	gold quality
left ovary	UBERON:0002119	68.96	gold quality
amygdala	UBERON:0001876	68.68	gold quality
temporal lobe	UBERON:0001871	68.66	gold quality
substantia nigra	UBERON:0002038	68.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	67.86	gold quality
right ovary	UBERON:0002118	67.59	gold quality
Ammon’s horn	UBERON:0001954	67.55	gold quality
prefrontal cortex	UBERON:0000451	66.83	gold quality
tibial nerve	UBERON:0001323	66.78	gold quality
right uterine tube	UBERON:0001302	66.59	gold quality
ovary	UBERON:0000992	66.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.26	gold quality
anterior cingulate cortex	UBERON:0009835	65.98	gold quality
popliteal artery	UBERON:0002250	65.69	gold quality
tibial artery	UBERON:0007610	65.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	37.47
E-MTAB-6142	no	10.08
E-ANND-3	no	0.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting NRN1L, 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-4492	99.87	68.25	3611
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6782-3P	97.60	67.75	931

Literature-anchored findings (GeneRIF, showing 1)

• CPG15 and CPG15-2 perform similar cellular functions but may play distinct roles in vivo through their cell-type- and tissue-specific transcriptional regulation. (PMID:18265009)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrn1lb	ENSDARG00000061149
danio_rerio	nrn1la	ENSDARG00000069368
mus_musculus	Nrn1l	ENSMUSG00000044287

Paralogs (1): NRN1 (ENSG00000124785)

Protein

Protein identifiers

Neuritin-like protein — Q496H8 (reviewed: Q496H8)

All UniProt accessions (3): Q496H8, I3L2K6, J3QS81

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Similarity. Belongs to the neuritin family.

RefSeq proteins (2): NP_001335611, NP_940845* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026144	Neuritin_fam	Family

Pfam: PF15056

UniProt features (4 total): signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q496H8-F1	73.23	0.32

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 139

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 56 (showing top): chr16q22, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_GROWTH, GOBP_NEUROGENESIS, FOXO1_01, NKX61_01, TGANTCA_AP1_C, NRF2_Q4, GOBP_DEVELOPMENTAL_CELL_GROWTH, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, CCCNNGGGAR_OLF1_01, GOBP_DEVELOPMENTAL_GROWTH_INVOLVED_IN_MORPHOGENESIS, NFE2_01, FOXO4_02

GO Biological Process (2): neuron projection extension (GO:1990138), nervous system development (GO:0007399)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), axon (GO:0030424), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
developmental cell growth	1
neuron projection morphogenesis	1
developmental growth involved in morphogenesis	1
system development	1
protein binding	1
binding	1
cell periphery	1
neuron projection	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

215 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRN1L	KIAA1143	Q96AT1	540
NRN1L	RPRML	Q8N4K4	526
NRN1L	TSTD1	Q8NFU3	428
NRN1L	PLA2G4F	Q68DD2	398
NRN1L	ZC3H3	Q8IXZ2	375
NRN1L	DIPK1A	Q5T7M9	374
NRN1L	SHROOM4	Q9ULL8	371
NRN1L	PLA2G4D	Q86XP0	366
NRN1L	CFAP65	Q6ZU64	358
NRN1L	CERCAM	Q5T4B2	351
NRN1L	SLC35A5	Q9BS91	350
NRN1L	SLC25A2	Q9BXI2	336
NRN1L	PLAC1	Q9HBJ0	330
NRN1L	MICALL2	Q8IY33	319
NRN1L	NUDT12	Q9BQG2	311

IntAct

5 interactions, top by confidence:

A	B	Type	Score
NRN1L	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
NRN1L	SLC39A10	psi-mi:“MI:0915”(physical association)	0.400
UBQLN2	NRN1L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): NRN1L (Reconstituted Complex), NRN1L (Two-hybrid), SLC39A10 (Affinity Capture-MS)

ESM2 similar proteins: A0MLS4, A2BDG0, A2BDG5, A2BDG9, A2RRL7, A3KN25, A6NGB7, G1TZA0, O14669, O77751, O77801, O95868, P01286, P02820, P02822, P0DUJ6, P24807, P25063, P27177, P41547, P51460, P63292, P98162, Q01524, Q08DF2, Q1ECT8, Q1JPW9, Q496H8, Q58CU5, Q5CZK3, Q5G860, Q5G863, Q5HZE8, Q60549, Q64697, Q6BEG6, Q7TPG6, Q8C4W3, Q8R182, Q923S2

Diamond homologs: O08957, Q2KIC6, Q496H8, Q5U523, Q6DGP8, Q8C4W3, Q8CFV4, Q90ZM9, Q9NPD7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

384 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67884979:CTCGG:C	donor_loss	1.0000
16:67884980:TCGGT:T	donor_loss	1.0000
16:67884981:CGGTG:C	donor_loss	1.0000
16:67884982:GGT:G	donor_loss	1.0000
16:67884983:G:GG	donor_gain	1.0000
16:67884983:G:T	donor_loss	1.0000
16:67884984:T:A	donor_loss	1.0000
16:67885721:GTCCT:G	acceptor_gain	1.0000
16:67885737:T:TA	acceptor_gain	1.0000
16:67884985:GAGT:G	donor_loss	0.9900
16:67885720:A:AG	acceptor_gain	0.9900
16:67885721:G:GG	acceptor_gain	0.9900
16:67885721:GTCC:G	acceptor_gain	0.9900
16:67885741:A:AG	acceptor_gain	0.9900
16:67885742:G:GG	acceptor_gain	0.9900
16:67885742:GCA:G	acceptor_gain	0.9900
16:67885850:TGCAG:T	donor_loss	0.9900
16:67885853:AGGTA:A	donor_loss	0.9900
16:67885855:G:GA	donor_loss	0.9900
16:67884978:CCTCG:C	donor_gain	0.9800
16:67884979:CTCG:C	donor_gain	0.9800
16:67884980:TCG:T	donor_gain	0.9800
16:67884981:CG:C	donor_gain	0.9800
16:67884982:GG:G	donor_gain	0.9800
16:67885738:G:A	acceptor_gain	0.9800
16:67885742:GC:G	acceptor_gain	0.9800
16:67885721:GTC:G	acceptor_gain	0.9700
16:67885721:GT:G	acceptor_gain	0.9500
16:67885834:C:T	donor_gain	0.9500
16:67885852:C:T	donor_gain	0.9500

AlphaMissense

1033 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67886046:G:C	W95C	0.995
16:67886046:G:T	W95C	0.995
16:67885980:G:C	W73C	0.992
16:67885980:G:T	W73C	0.992
16:67885987:T:C	F76L	0.984
16:67885989:C:A	F76L	0.984
16:67885989:C:G	F76L	0.984
16:67885988:T:G	F76C	0.983
16:67885788:T:G	F49C	0.982
16:67885787:T:C	F49L	0.973
16:67885789:C:A	F49L	0.973
16:67885789:C:G	F49L	0.973
16:67885788:T:C	F49S	0.967
16:67885978:T:A	W73R	0.961
16:67885978:T:C	W73R	0.961
16:67885988:T:C	F76S	0.959
16:67886044:T:A	W95R	0.956
16:67886044:T:C	W95R	0.956
16:67886093:T:C	L111S	0.950
16:67885796:T:C	C52R	0.948
16:67886104:T:A	C115S	0.945
16:67886105:G:C	C115S	0.945
16:67885850:T:A	C70S	0.943
16:67885851:G:C	C70S	0.943
16:67886000:C:A	A80D	0.943
16:67885796:T:A	C52S	0.942
16:67885797:G:C	C52S	0.942
16:67885800:T:A	L53H	0.940
16:67885812:G:T	G57V	0.939
16:67886020:T:A	C87S	0.933

dbSNP variants (sampled 300 via entrez): RS1001308848 (16:67883857 C>T), RS1002574737 (16:67887555 C>G), RS1002623305 (16:67887066 G>A), RS1002830792 (16:67888816 A>G), RS1003218996 (16:67887052 G>A), RS1004112170 (16:67889336 T>A,C,G), RS1004146088 (16:67886413 G>A,T), RS1004496431 (16:67886774 C>T), RS1004657234 (16:67884738 G>C), RS1005637898 (16:67887860 G>A), RS1005764997 (16:67885648 C>G,T), RS1006231663 (16:67885506 C>G), RS1006512898 (16:67884673 C>G), RS1006612826 (16:67885201 G>A), RS1007058327 (16:67888710 G>T)

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

2 associations (top):

Study	Trait	p-value
GCST002539_84	Schizophrenia	2.000000e-08
GCST006803_42	Schizophrenia	4.000000e-08

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
Cisplatin	affects expression, affects cotreatment, decreases expression	2
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Benzo(a)pyrene	increases methylation	1
Fonofos	increases methylation	1
Gallic Acid	decreases expression	1
Parathion	increases methylation	1
Silver	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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