NGRN

Summary

NGRN (neugrin, neurite outgrowth associated, HGNC:18077) is a protein-coding gene on chromosome 15q26.1, encoding Neugrin (Q9NPE2). Plays an essential role in mitochondrial ribosome biogenesis. It is a selective cancer dependency (DepMap: 10.8% of cell lines).

Enables rRNA binding activity. Involved in mitochondrial ribosome assembly and positive regulation of mitochondrial translation. Located in several cellular components, including mitochondrion; mitotic spindle; and nuclear body.

Source: NCBI Gene 51335 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 51 total
• Cancer dependency (DepMap): dependent in 10.8% of screened cell lines
• MANE Select transcript: NM_001033088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18077
Approved symbol	NGRN
Name	neugrin, neurite outgrowth associated
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	DSC92
Ensembl gene	ENSG00000182768
Ensembl biotype	protein_coding
OMIM	616718
Entrez	51335

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000331497, ENST00000379095, ENST00000411845, ENST00000885215, ENST00000885216, ENST00000939262, ENST00000961528

RefSeq mRNA: 1 — MANE Select: NM_001033088 NM_001033088

CCDS: CCDS32329

Canonical transcript exons

ENST00000379095 — 3 exons

Exon	Start	End
ENSE00001479750	90265672	90265876
ENSE00001605534	90271188	90272211
ENSE00003638144	90266288	90266398

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.8267 / max 943.8670, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148429	60.4286	1822
148430	11.0742	1781
148432	1.4928	946
148433	0.5795	253
148434	0.5357	155
148437	0.5346	263
148431	0.1812	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsolateral prefrontal cortex	UBERON:0009834	99.51	gold quality
superior frontal gyrus	UBERON:0002661	99.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.46	gold quality
right frontal lobe	UBERON:0002810	99.45	gold quality
prefrontal cortex	UBERON:0000451	99.44	gold quality
frontal cortex	UBERON:0001870	99.43	gold quality
cerebral cortex	UBERON:0000956	99.39	gold quality
primary visual cortex	UBERON:0002436	99.39	gold quality
cortical plate	UBERON:0005343	99.36	gold quality
nucleus accumbens	UBERON:0001882	99.35	gold quality
hypothalamus	UBERON:0001898	99.35	gold quality
amygdala	UBERON:0001876	99.33	gold quality
caudate nucleus	UBERON:0001873	99.32	gold quality
putamen	UBERON:0001874	99.32	gold quality
temporal lobe	UBERON:0001871	99.30	gold quality
anterior cingulate cortex	UBERON:0009835	99.23	gold quality
Ammon’s horn	UBERON:0001954	99.21	gold quality
ganglionic eminence	UBERON:0004023	99.21	gold quality
brain	UBERON:0000955	99.19	gold quality
substantia nigra	UBERON:0002038	99.19	gold quality
gastrocnemius	UBERON:0001388	99.12	gold quality
muscle of leg	UBERON:0001383	99.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.92	gold quality
ventricular zone	UBERON:0003053	98.91	gold quality
cerebellar cortex	UBERON:0002129	98.83	gold quality
cerebellar hemisphere	UBERON:0002245	98.83	gold quality
cerebellum	UBERON:0002037	98.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.72	gold quality
skeletal muscle tissue	UBERON:0001134	98.57	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	1251.11
E-HCAD-10	yes	4.70
E-HCAD-5	no	15.41
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting NGRN, 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-4803	99.98	71.99	3117
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-602	97.09	61.68	156

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.8% of screened cell lines.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ngrn	ENSDARG00000061314
mus_musculus	Ngrn	ENSMUSG00000047084
rattus_norvegicus	Ngrn	ENSRNOG00000013553

Protein

Protein identifiers

Neugrin — Q9NPE2 (reviewed: Q9NPE2)

Alternative names: Mesenchymal stem cell protein DSC92, Neurite outgrowth-associated protein, Spinal cord-derived protein FI58G

All UniProt accessions (2): A0A087WWE0, Q9NPE2

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in mitochondrial ribosome biogenesis. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation of core subunits of the oxidative phosphorylation system.

Subunit / interactions. Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA. Interacts with 16S mt-rRNA; this interaction is direct.

Subcellular location. Nucleus. Secreted. Mitochondrion membrane.

Tissue specificity. Expressed at high levels in heart, brain and skeletal muscle. In brain, mainly expressed in neurons rather than glial cells.

Induction. Highly up-regulated in neuroblastostoma cells by retinoic acid treatment inducing neurite outgrowth.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the neugrin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPE2-2	1	yes
Q9NPE2-3	2

RefSeq proteins (1): NP_001028260* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010487	NGRN/Rrg9	Family

Pfam: PF06413

UniProt features (15 total): glycosylation site 3, splice variant 2, sequence variant 2, sequence conflict 2, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPE2-F1	68.87	0.35

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): 41

Glycosylation sites (3): 158, 186, 268

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6793080	rRNA modification in the mitochondrion
R-HSA-9937008	Mitochondrial mRNA modification

MSigDB gene sets: 152 (showing top): GCM_MAP4K4, GOBP_RIBOSOME_BIOGENESIS, GCM_GSPT1, GCM_ZNF198, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_RIBOSOME_ASSEMBLY, GOBP_NEUROGENESIS, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANELLE_ASSEMBLY, GCM_SUFU, GCM_CALM1, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (4): neuron differentiation (GO:0030182), mitochondrial ribosome assembly (GO:0061668), positive regulation of mitochondrial translation (GO:0070131), cell differentiation (GO:0030154)

GO Molecular Function (3): RNA binding (GO:0003723), rRNA binding (GO:0019843), protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), nuclear body (GO:0016604), mitochondrial membrane (GO:0031966), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
rRNA processing in the mitochondrion	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	2
mitochondrion	2
cell differentiation	1
generation of neurons	1
ribosome assembly	1
mitochondrial translation	1
positive regulation of translation	1
regulation of mitochondrial translation	1
cellular developmental process	1
nucleic acid binding	1
RNA binding	1
binding	1
nuclear lumen	1
cytoplasm	1
intracellular organelle lumen	1
nucleoplasm	1
intracellular membraneless organelle	1
mitochondrial envelope	1
organelle membrane	1
spindle	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NGRN	RPUSD4	Q96CM3	877
NGRN	FASTKD2	Q9NYY8	861
NGRN	RPUSD3	Q6P087	846
NGRN	TRUB2	O95900	784
NGRN	RCC1L	Q96I51	779
NGRN	PTCD1	O75127	761
NGRN	GTPBP10	A4D1E9	676
NGRN	MRM3	Q9HC36	676
NGRN	NRGN	Q92686	575
NGRN	MTERF3	Q96E29	572
NGRN	MTG2	Q9H4K7	564
NGRN	MALSU1	Q96EH3	555
NGRN	DDX28	Q9NUL7	514
NGRN	MTERF4	Q7Z6M4	512
NGRN	NSUN4	Q96CB9	476

IntAct

126 interactions, top by confidence:

A	B	Type	Score
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
GTF2H5	NGRN	psi-mi:“MI:0915”(physical association)	0.560
YOD1	NGRN	psi-mi:“MI:0915”(physical association)	0.560
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
RBM3	PRMT5	psi-mi:“MI:0914”(association)	0.530
CIRBP	PRMT5	psi-mi:“MI:0914”(association)	0.530
RPL7	ZBTB24	psi-mi:“MI:0914”(association)	0.530
MRPL42	GATC	psi-mi:“MI:0914”(association)	0.530
RPL6	MRPS14	psi-mi:“MI:0914”(association)	0.530
RBMX	PTCD1	psi-mi:“MI:0914”(association)	0.530
DDX28	PTCD1	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530
HNRNPA1	PTCD1	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	psi-mi:“MI:0914”(association)	0.530
NGRN	RPL7	psi-mi:“MI:0914”(association)	0.530
RBM3	AARS2	psi-mi:“MI:0914”(association)	0.530
MRPL13	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SRSF3	CASC3	psi-mi:“MI:0914”(association)	0.530
NGRN	DCTD	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (300): NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), NGRN (Affinity Capture-MS), WBSCR16 (Affinity Capture-MS), RPUSD3 (Affinity Capture-MS)

ESM2 similar proteins: A0JPN4, A2AKB4, A6NDY0, A6NP61, A7E321, B0BNE4, B1ASB6, O54824, O88286, O95931, P60924, Q14005, Q14154, Q1XFL1, Q3T1H2, Q3TYG6, Q3ZBR0, Q49AM3, Q4R2Z8, Q4R747, Q4VXA5, Q5R7E7, Q5SU73, Q5SXM2, Q5SYB0, Q5XFR0, Q6NVP7, Q6P1D7, Q6ZUX3, Q7Z572, Q7ZXB8, Q80VM8, Q8BG34, Q8BIY3, Q8BLK9, Q8BP86, Q8IY92, Q8K124, Q93075, Q96FV0

Diamond homologs: A1C6R8, A1DHD8, A2QCR5, A3LTV8, A5DKF1, A5DZ02, A6ZRM7, A7EJ50, A7TIC4, B0XSW5, B2W722, B3LP57, B5VQJ9, B6HDT2, B6QGW6, B8MLF7, B8NHF2, C0SC25, C1GIF2, C4JXN2, C4R331, C5DD31, C5DTR1, C5FNG9, C5GEF3, C5JS82, C5PBQ8, C7GPE4, C8ZG19, D1ZQ10, D4AKN8, D4DHC4, E3L408, E3REX1, E4UQC3, O14211, P0C8Z6, P40156, Q0CYR5, Q0TY47

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial translation initiation	15	27.2×	6e-16
Mitochondrial translation elongation	15	27.2×	6e-16
Mitochondrial ribosome-associated quality control	15	26.3×	6e-16
Mitochondrial translation	12	23.6×	4e-12
Mitochondrial translation termination	15	23.5×	3e-15
Translation	14	12.4×	2e-10
Transport of Mature mRNA derived from an Intron-Containing Transcript	5	10.9×	2e-03
Processing of Capped Intron-Containing Pre-mRNA	9	10.6×	6e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	5	36.8×	3e-05
mitochondrial translation	17	28.4×	8e-18
positive regulation of mRNA splicing, via spliceosome	5	26.1×	1e-04
regulation of alternative mRNA splicing, via spliceosome	6	14.1×	3e-04
mRNA transport	5	12.7×	3e-03
translation	12	11.9×	9e-08
RNA processing	5	10.5×	5e-03
mRNA splicing, via spliceosome	9	7.9×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

745 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90265866:G:GT	donor_gain	1.0000
15:90266394:A:G	donor_gain	0.9900
15:90265856:G:GT	donor_gain	0.9800
15:90265874:G:GT	donor_gain	0.9800
15:90265874:GAGGT:G	donor_loss	0.9800
15:90265876:GGTAC:G	donor_loss	0.9800
15:90265877:G:T	donor_loss	0.9800
15:90266286:A:AG	acceptor_gain	0.9800
15:90266287:G:GG	acceptor_gain	0.9800
15:90265870:TGGAG:T	donor_gain	0.9700
15:90265874:GAG:G	donor_gain	0.9700
15:90266287:GC:G	acceptor_gain	0.9700
15:90266394:ATACG:A	donor_loss	0.9700
15:90266396:ACG:A	donor_loss	0.9700
15:90266397:CGGTG:C	donor_loss	0.9700
15:90266398:GGTGA:G	donor_loss	0.9700
15:90266399:G:GG	donor_gain	0.9700
15:90266399:GTGAG:G	donor_loss	0.9700
15:90266400:TGAGA:T	donor_loss	0.9700
15:90266401:GAGAC:G	donor_loss	0.9700
15:90266410:GA:G	donor_gain	0.9700
15:90266692:GCA:G	donor_gain	0.9700
15:90265852:A:T	donor_gain	0.9600
15:90266287:GCA:G	acceptor_gain	0.9600
15:90266287:GCACC:G	acceptor_gain	0.9600
15:90266403:G:C	donor_loss	0.9600
15:90266693:C:T	donor_gain	0.9600
15:90267618:GGC:G	donor_gain	0.9600
15:90267619:GCG:G	donor_gain	0.9600
15:90265871:GGAGA:G	donor_gain	0.9500

AlphaMissense

1885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90271243:T:C	F111L	0.994
15:90271245:T:A	F111L	0.994
15:90271245:T:G	F111L	0.994
15:90271232:T:C	L107S	0.990
15:90271235:C:A	A108D	0.984
15:90271193:T:C	L94S	0.981
15:90266395:T:C	I91T	0.980
15:90271216:T:A	W102R	0.979
15:90271216:T:C	W102R	0.979
15:90271288:T:C	F126L	0.978
15:90271290:T:A	F126L	0.978
15:90271290:T:G	F126L	0.978
15:90271274:T:A	V121D	0.972
15:90271234:G:C	A108P	0.971
15:90266398:G:C	R92P	0.967
15:90271244:T:C	F111S	0.965
15:90271265:T:A	I118N	0.965
15:90271218:G:C	W102C	0.964
15:90271218:G:T	W102C	0.964
15:90271750:T:C	F280L	0.963
15:90271752:C:A	F280L	0.963
15:90271752:C:G	F280L	0.963
15:90271272:A:C	R120S	0.962
15:90271272:A:T	R120S	0.962
15:90266366:G:C	R81S	0.958
15:90266366:G:T	R81S	0.958
15:90266382:G:C	A87P	0.957
15:90271250:T:A	V113D	0.957
15:90271243:T:A	F111I	0.954
15:90266395:T:A	I91K	0.948

dbSNP variants (sampled 300 via entrez): RS1000280670 (15:90267815 A>G), RS1000284543 (15:90268000 CGTTTGTTT>C,CGTTT,CGTTTGTTTGTTT), RS1000696502 (15:90268020 G>A), RS1003068902 (15:90269924 A>G), RS1003409078 (15:90271312 C>A), RS1003452079 (15:90269672 C>A,G,T), RS1003684193 (15:90263726 C>A,T), RS1004854797 (15:90265293 A>G,T), RS1005473924 (15:90267116 C>G), RS1006041786 (15:90271905 T>C), RS1006365562 (15:90265950 G>A,T), RS1006469759 (15:90265649 G>A,T), RS1006948112 (15:90270398 C>T), RS1007260590 (15:90267779 A>G), RS1007486289 (15:90264497 C>G,T)

Disease associations

OMIM: gene MIM:616718 | 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
GCST009597_254	Multiple sclerosis	1.000000e-12
GCST012481_11	Cerebral amyloid angiopathy in Alzheimer’s disease	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
epigallocatechin gallate	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	affects expression	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Sarin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Zinc	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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