METRN

Summary

METRN (meteorin, glial cell differentiation regulator, HGNC:14151) is a protein-coding gene on chromosome 16p13.3, encoding Meteorin (Q9UJH8). Involved in both glial cell differentiation and axonal network formation during neurogenesis.

Meteorin regulates glial cell differentiation and promotes the formation of axonal networks during neurogenesis (Nishino et al., 2004 [PubMed 15085178]).

Source: NCBI Gene 79006 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 92 total
• MANE Select transcript: NM_024042

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14151
Approved symbol	METRN
Name	meteorin, glial cell differentiation regulator
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC2601
Ensembl gene	ENSG00000103260
Ensembl biotype	protein_coding
OMIM	610998
Entrez	79006

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000219542, ENST00000564661, ENST00000567076, ENST00000568223, ENST00000568415, ENST00000570132, ENST00000936477

RefSeq mRNA: 1 — MANE Select: NM_024042 NM_024042

CCDS: CCDS10422

Canonical transcript exons

ENST00000568223 — 4 exons

Exon	Start	End
ENSE00000664200	715584	715984
ENSE00000945860	715118	715393
ENSE00002608616	717071	719655
ENSE00003556169	716933	716992

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 98.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.4234 / max 269.6695, expressed in 1684 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151979	22.5922	1683
151980	0.6546	321
151981	0.1766	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.99	gold quality
right uterine tube	UBERON:0001302	98.81	gold quality
spinal cord	UBERON:0002240	98.73	gold quality
caudate nucleus	UBERON:0001873	98.64	gold quality
nucleus accumbens	UBERON:0001882	98.64	gold quality
amygdala	UBERON:0001876	98.61	gold quality
right frontal lobe	UBERON:0002810	97.99	gold quality
putamen	UBERON:0001874	97.83	gold quality
anterior cingulate cortex	UBERON:0009835	97.73	gold quality
cingulate cortex	UBERON:0003027	97.71	gold quality
ventral tegmental area	UBERON:0002691	97.68	gold quality
adenohypophysis	UBERON:0002196	97.54	gold quality
hypothalamus	UBERON:0001898	97.53	gold quality
prefrontal cortex	UBERON:0000451	96.98	gold quality
inferior vagus X ganglion	UBERON:0005363	96.97	gold quality
decidua	UBERON:0002450	96.86	gold quality
apex of heart	UBERON:0002098	96.84	gold quality
superior vestibular nucleus	UBERON:0007227	96.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.40	gold quality
tibial nerve	UBERON:0001323	96.37	gold quality
pituitary gland	UBERON:0000007	96.25	gold quality
subthalamic nucleus	UBERON:0001906	95.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.70	gold quality
forebrain	UBERON:0001890	95.55	gold quality
cerebellar cortex	UBERON:0002129	95.50	gold quality
cerebellar hemisphere	UBERON:0002245	95.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.50	gold quality
frontal cortex	UBERON:0001870	95.45	gold quality
Ammon’s horn	UBERON:0001954	95.42	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	3569.40
E-GEOD-137537	yes	2337.83
E-MTAB-9435	yes	1958.61
E-HCAD-56	yes	1049.56
E-MTAB-10485	yes	575.23
E-ANND-3	yes	4.77
E-MTAB-10018	no	431.77
E-MTAB-9154	no	229.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting METRN, 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-4425	100.00	67.59	1049
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-661	99.09	65.94	2062

Literature-anchored findings (GeneRIF, showing 4)

• Meteorin plays important roles in both glial cell differentiation and axonal network formation during neurogenesis. (PMID:15085178)
• The joint measurements of circulating METRN levels in the first trimester and systolic blood pressure and weight in the second trimester significantly increase the probabilities of predicting preeclampsia. (PMID:26121675)
• Over expression of METRN predicts poor clinical prognosis in colorectal cancer. (PMID:31859449)
• Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRalpha pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance. (PMID:33867829)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	metrn	ENSDARG00000030367
mus_musculus	Metrn	ENSMUSG00000002274
rattus_norvegicus	Metrn	ENSRNOG00000019692

Paralogs (1): METRNL (ENSG00000176845)

Protein

Protein identifiers

Meteorin — Q9UJH8 (reviewed: Q9UJH8)

All UniProt accessions (5): Q9UJH8, H3BSC8, H3BUM1, I3L2T3, J3KMW6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in both glial cell differentiation and axonal network formation during neurogenesis. Promotes astrocyte differentiation and transforms cerebellar astrocytes into radial glia. Also induces axonal extension in small and intermediate neurons of sensory ganglia by activating nearby satellite glia.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Similarity. Belongs to the meteorin family.

RefSeq proteins (1): NP_076947* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051998	Meteorin-like	Family

UniProt features (7 total): disulfide bond 5, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJH8-F1	82.95	0.49

Functional residue map

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

Disulfide bonds (5): 30–51, 82–118, 171–242, 174–266, 184–288

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, PRAMOONJAGO_SOX4_TARGETS_DN, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, SMID_BREAST_CANCER_LUMINAL_B_UP, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, WCTCNATGGY_UNKNOWN, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, VDR_Q3, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_GLIAL_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS

GO Biological Process (7): axonogenesis (GO:0007409), glial cell differentiation (GO:0010001), positive regulation of axonogenesis (GO:0050772), radial glial cell differentiation (GO:0060019), signal transduction (GO:0007165), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (1): hormone activity (GO:0005179)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
cell differentiation	1
gliogenesis	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
glial cell differentiation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
cellular developmental process	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METRN	FNDC5	Q8NAU1	699
METRN	BDNF	P23560	584
METRN	NTF3	P20783	579
METRN	PRR35	P0CG20	517
METRN	UCP1	P25874	509
METRN	NGF	P01138	507
METRN	FGF21	Q9NSA1	507
METRN	KBTBD12	Q3ZCT8	466
METRN	VWC2	Q2TAL6	461
METRN	MSTN	O14793	453
METRN	RRP36	Q96EU6	445
METRN	TOGARAM1	Q9Y4F4	428
METRN	IHO1	Q8IYA8	417
METRN	RUSC1	Q9BVN2	415
METRN	KCNG3	Q8TAE7	412

IntAct

46 interactions, top by confidence:

A	B	Type	Score
DNASE1L2	HSPA5	psi-mi:“MI:0914”(association)	0.620
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
SERPINA6	METRN	psi-mi:“MI:0915”(physical association)	0.400
METRN	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
A2M	PZP	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
A2M	BMP7	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
PI15		psi-mi:“MI:0914”(association)	0.350
ISLR		psi-mi:“MI:0914”(association)	0.350
PTPRN	KCNK1	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
FMOD	QSOX1	psi-mi:“MI:0914”(association)	0.350
CRLF1	MANBA	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-RNA), METRN (Two-hybrid), METRN (Affinity Capture-RNA), METRN (Affinity Capture-RNA), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS), METRN (Affinity Capture-MS)

ESM2 similar proteins: A0A5F4BST2, A0PJX4, A0RZB4, A1L515, A2A9Q0, A2BDG0, A6QQ85, A6XN32, A9JSM3, B0FP48, D3YZZ2, D4A2Q0, E5RIL1, F1SAM7, P01183, Q1RMK9, Q3UPR0, Q3ZCQ3, Q5BIV7, Q5BIV9, Q5BK01, Q5GH56, Q5GH64, Q5GH72, Q5SNT2, Q5T7M4, Q6IEE6, Q6PRD1, Q6UWJ8, Q70RD5, Q864V4, Q86UD0, Q8BWU1, Q8BX43, Q8CCB5, Q8IVY1, Q8K064, Q8K2Y3, Q8K5A9, Q8N9H8

Diamond homologs: A1L2K1, Q5Q0T9, Q5RJL6, Q641Q3, Q7ZV46, Q8C1Q4, Q8VE43, Q9UJH8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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
Extracellular matrix organization	6	9.2×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	5	20.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

571 predictions. Top by Δscore:

Variant	Effect	Δscore
16:715981:GACG:G	donor_gain	1.0000
16:715983:CGGTG:C	donor_loss	1.0000
16:715985:G:GA	donor_loss	1.0000
16:715985:G:GG	donor_gain	1.0000
16:715986:T:G	donor_loss	1.0000
16:715983:CG:C	donor_gain	0.9900
16:715984:GG:G	donor_gain	0.9900
16:716474:G:T	donor_gain	0.9900
16:717069:A:AG	acceptor_gain	0.9900
16:717070:G:GG	acceptor_gain	0.9900
16:715982:ACG:A	donor_gain	0.9800
16:716473:GGA:G	donor_gain	0.9800
16:717070:GTA:G	acceptor_gain	0.9800
16:715971:TCTCG:T	donor_gain	0.9700
16:715980:AGACG:A	donor_gain	0.9700
16:715981:GACGG:G	donor_gain	0.9700
16:716474:G:GT	donor_gain	0.9600
16:716928:GCCA:G	acceptor_loss	0.9600
16:716929:CCA:C	acceptor_loss	0.9600
16:716930:CA:C	acceptor_loss	0.9600
16:716931:A:AC	acceptor_loss	0.9600
16:716932:G:GT	acceptor_loss	0.9600
16:716932:GGT:G	acceptor_gain	0.9600
16:716932:GGTGC:G	acceptor_gain	0.9600
16:715987:GAGTG:G	donor_loss	0.9500
16:716931:A:AG	acceptor_gain	0.9500
16:716932:G:GG	acceptor_gain	0.9500
16:717070:GT:G	acceptor_gain	0.9500
16:716931:AG:A	acceptor_gain	0.9400
16:716931:AGGT:A	acceptor_gain	0.9400

AlphaMissense

1851 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:715653:G:C	W58C	0.977
16:715653:G:T	W58C	0.977
16:715868:T:G	F130C	0.977
16:715385:G:C	W32C	0.970
16:715385:G:T	W32C	0.970
16:715867:T:C	F130L	0.969
16:715869:C:A	F130L	0.969
16:715869:C:G	F130L	0.969
16:717322:T:C	F273L	0.968
16:717324:C:A	F273L	0.968
16:717324:C:G	F273L	0.968
16:715762:T:C	F95L	0.963
16:715764:C:A	F95L	0.963
16:715764:C:G	F95L	0.963
16:715921:T:C	F148L	0.959
16:715923:T:A	F148L	0.959
16:715923:T:G	F148L	0.959
16:715651:T:A	W58R	0.958
16:715651:T:C	W58R	0.958
16:715915:T:C	F146L	0.956
16:715916:T:C	F146S	0.956
16:715917:C:A	F146L	0.956
16:715917:C:G	F146L	0.956
16:715763:T:G	F95C	0.946
16:715916:T:G	F146C	0.946
16:715744:T:C	F89L	0.945
16:715746:C:A	F89L	0.945
16:715746:C:G	F89L	0.945
16:717256:T:C	F251L	0.944
16:717258:C:A	F251L	0.944

dbSNP variants (sampled 300 via entrez): RS1000567164 (16:713622 C>A,G), RS1000578260 (16:713888 T>C), RS1001158385 (16:717240 C>A,G), RS1001191934 (16:719335 C>G), RS1001250614 (16:715406 G>A,C,T), RS1001853954 (16:717415 A>C,G,T), RS1002457134 (16:716722 G>A), RS1002583720 (16:716458 G>A,C), RS1003000343 (16:719237 C>G,T), RS1003136097 (16:713566 A>G), RS1003179549 (16:714957 C>A,G,T), RS1003284900 (16:719529 G>A), RS1003317594 (16:719786 A>C,G), RS1003590116 (16:716145 G>A), RS1003595447 (16:716327 C>G,T)

Disease associations

OMIM: gene MIM:610998 | 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
GCST012226_128	Waist circumference adjusted for body mass index	7.000000e-11
GCST012227_357	Hip circumference adjusted for BMI	7.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	5
sodium arsenite	increases expression, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
dicrotophos	decreases expression	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
bleomycetin	increases expression	1
exemestane	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	decreases expression	1
deguelin	decreases expression	1
K 7174	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
thifluzamide	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Antimycin A	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Cyclophosphamide	affects response to substance, affects cotreatment	1
Doxorubicin	affects cotreatment, affects response to substance	1
Fluorouracil	affects cotreatment, affects response to substance	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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