GMFB

Summary

GMFB (glia maturation factor beta, HGNC:4373) is a protein-coding gene on chromosome 14q22.2, encoding Glia maturation factor beta (P60983). This protein causes differentiation of brain cells, stimulation of neural regeneration, and inhibition of proliferation of tumor cells.

Predicted to enable Arp2/3 complex binding activity. Predicted to be involved in actin filament debranching and negative regulation of Arp2/3 complex-mediated actin nucleation. Predicted to act upstream of or within learning and locomotory behavior. Predicted to be active in cortical actin cytoskeleton.

Source: NCBI Gene 2764 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 22 total — 1 pathogenic
• MANE Select transcript: NM_004124

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4373
Approved symbol	GMFB
Name	glia maturation factor beta
Location	14q22.2
Locus type	gene with protein product
Status	Approved
Aliases	GMF
Ensembl gene	ENSG00000197045
Ensembl biotype	protein_coding
OMIM	601713
Entrez	2764

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000358056, ENST00000553333, ENST00000553566, ENST00000553952, ENST00000554163, ENST00000554247, ENST00000554682, ENST00000554908, ENST00000628554, ENST00000866823, ENST00000932199, ENST00000942924

RefSeq mRNA: 1 — MANE Select: NM_004124 NM_004124

CCDS: CCDS9718

Canonical transcript exons

ENST00000358056 — 7 exons

Exon	Start	End
ENSE00001375419	54480874	54480956
ENSE00001920762	54474485	54478159
ENSE00003562267	54483671	54483767
ENSE00003597735	54479786	54479859
ENSE00003603200	54482153	54482202
ENSE00003625586	54481409	54481458
ENSE00003690381	54488925	54488980

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.0254 / max 1484.7063, expressed in 1807 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143320	32.0792	1798
143321	6.3692	1617
143318	0.3160	104
143317	0.1452	46
143319	0.1158	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.16	gold quality
cranial nerve II	UBERON:0000941	99.07	gold quality
middle temporal gyrus	UBERON:0002771	99.07	gold quality
medial globus pallidus	UBERON:0002477	98.99	gold quality
globus pallidus	UBERON:0001875	98.92	gold quality
CA1 field of hippocampus	UBERON:0003881	98.78	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.68	gold quality
secondary oocyte	CL:0000655	98.67	gold quality
subthalamic nucleus	UBERON:0001906	98.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.64	gold quality
lateral globus pallidus	UBERON:0002476	98.62	gold quality
medulla oblongata	UBERON:0001896	98.60	gold quality
inferior olivary complex	UBERON:0002127	98.59	gold quality
entorhinal cortex	UBERON:0002728	98.54	gold quality
substantia nigra pars compacta	UBERON:0001965	98.49	gold quality
inferior vagus X ganglion	UBERON:0005363	98.44	gold quality
oocyte	CL:0000023	98.39	gold quality
endothelial cell	CL:0000115	98.39	gold quality
orbitofrontal cortex	UBERON:0004167	98.36	gold quality
superior vestibular nucleus	UBERON:0007227	98.31	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.07	gold quality
trigeminal ganglion	UBERON:0001675	98.01	gold quality
parietal lobe	UBERON:0001872	97.83	gold quality
pons	UBERON:0000988	97.80	gold quality
postcentral gyrus	UBERON:0002581	97.80	gold quality
corpus callosum	UBERON:0002336	97.79	gold quality
germinal epithelium of ovary	UBERON:0001304	97.77	gold quality
olfactory bulb	UBERON:0002264	97.76	gold quality
superior frontal gyrus	UBERON:0002661	97.76	gold quality
parietal pleura	UBERON:0002400	97.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

234 targeting GMFB, 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-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 11)

• GMFB promoted T-cell differentiation into CD4-/CD8+ cells when analysed by two-colour flow cytometry. (PMID:16115230)
• There is a significant increase in GMF beta protein expression levels in IFN beta-1a treated LX-2 cells. (PMID:18171522)
• GMF co-localizes with amyloid plaques and neurofibrillary tangles in Alzheimer brains, implicating significant upregulation of GMF expression under conditions of neurodegeneration. (PMID:21835226)
• The distribution of GMF-immunoreactive cells in and around amyloid plaques and neurofibrillary tangles suggests involvement of GMF in inflammatory responses through reactive glia and a role of GMF in Alzheimer disease pathology. (PMID:22035352)
• GMF-beta is an important player in glioma progression via promoting neovascularization. (PMID:26515590)
• GMF and ApoE4 were strongly expressed and co-associated in amyloid plaques (APs) and in the reactive astrocytes surrounding APs in Alzheimer’s disease. (PMID:29172001)
• GMF acts as an important upstream regulator of PGC-1alpha in promoting dopaminergic neuronal death through its effect on oxidative stress-mediated apoptosis. (PMID:29383690)
• MicroRNA-5195-3p alleviates high glucoseinduced injury in human ARPE-19 cells by targeting GMFB. (PMID:34793551)
• G9a Inhibition Promotes Neuroprotection through GMFB Regulation in Alzheimer’s Disease. (PMID:37307824)
• Parkinson’s Disease Dementia Patients: Expression of Glia Maturation Factor in the Brain. (PMID:38256254)
• SUMOylation of GMFB regulates its stability and function in retinal pigment epithelial cells under hyperglycemia. (PMID:38657921)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gmfb	ENSDARG00000028327
mus_musculus	Gmfb	ENSMUSG00000062014
rattus_norvegicus	Gmfb	ENSRNOG00000064480
drosophila_melanogaster	GMF	FBGN0028894
caenorhabditis_elegans		WBGENE00021758

Paralogs (1): GMFG (ENSG00000130755)

Protein

Protein identifiers

Glia maturation factor beta — P60983 (reviewed: P60983)

All UniProt accessions (3): P60983, G3V3X4, G3V4P8

UniProt curated annotations — full annotation on UniProt →

Function. This protein causes differentiation of brain cells, stimulation of neural regeneration, and inhibition of proliferation of tumor cells.

Post-translational modifications. Phosphorylated; stimulated by phorbol ester.

Similarity. Belongs to the actin-binding proteins ADF family. GMF subfamily.

RefSeq proteins (1): NP_004115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002108	ADF-H	Domain
IPR011171	GMF	Family
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily

Pfam: PF00241

UniProt features (4 total): initiator methionine 1, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60983-F1	94.24	0.92

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 286 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_COGNITION, MORF_MBD4, GOBP_BEHAVIOR, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_RAB5A, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_RAD21, GOMF_GROWTH_FACTOR_ACTIVITY

GO Biological Process (7): protein phosphorylation (GO:0006468), nervous system development (GO:0007399), learning (GO:0007612), locomotory behavior (GO:0007626), negative regulation of Arp2/3 complex-mediated actin nucleation (GO:0034316), actin filament debranching (GO:0071846), signal transduction (GO:0007165)

GO Molecular Function (5): actin binding (GO:0003779), protein kinase inhibitor activity (GO:0004860), enzyme activator activity (GO:0008047), growth factor activity (GO:0008083), Arp2/3 complex binding (GO:0071933)

GO Cellular Component (1): cortical actin cytoskeleton (GO:0030864)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphorylation	1
protein modification process	1
system development	1
learning or memory	1
behavior	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
negative regulation of actin nucleation	1
actin filament severing	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytoskeletal protein binding	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
receptor ligand activity	1
protein-containing complex binding	1
actin cytoskeleton	1
cortical cytoskeleton	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

15 interactions, top by confidence:

A	B	Type	Score
GMFB	GMFG	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
GRB2	MYO1C	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
AHSP	GMFB	psi-mi:“MI:0914”(association)	0.350
BCAS2	ISY1-RAB43	psi-mi:“MI:0914”(association)	0.350
CORO2B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
GMFB	RIPK2	psi-mi:“MI:0914”(association)	0.350
IL2RG	BBOX1	psi-mi:“MI:0914”(association)	0.350
TRAF6	GMFB	psi-mi:“MI:0915”(physical association)	0.000
GMFB	IKBKE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): GMFB (Co-fractionation), GMFB (Co-fractionation), GMFB (Co-fractionation), HNRNPH2 (Co-fractionation), PFDN6 (Co-fractionation), SETD3 (Co-fractionation), GMFB (Affinity Capture-MS), GMFB (Affinity Capture-Western), GMFG (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), GMFB (Affinity Capture-Western), MAPK3 (Affinity Capture-Western), ALAD (Affinity Capture-MS), CARM1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS)

ESM2 similar proteins: A4FUD6, B0BN93, B5DGH9, O60234, O80526, P10668, P18760, P21566, P23528, P45591, P45592, P60983, P60984, P84169, Q05AY2, Q148F1, Q15437, Q1LUA8, Q28C65, Q2QNG7, Q3B8M3, Q3SZN2, Q3T102, Q4R5C0, Q4R6G8, Q56JZ9, Q5E964, Q5E9F7, Q5G6V9, Q5R5G2, Q5R6P6, Q5RCC1, Q5U4Y2, Q5XHH8, Q5ZK03, Q5ZLA5, Q63228, Q6B7M7, Q6DRI1, Q6GNI4

Diamond homologs: O13808, O60234, P60983, P60984, Q56JZ9, Q5R6P6, Q63228, Q80T18, Q9CQI3, Q9ERL7, Q9VJL6, O94399, Q17A58, C4LVG4, P78929, Q12792, Q298X4, Q56JV6, Q5I082, Q5R7N2, Q5RFH1, Q5RJR2, Q5ZM35, Q640W2, Q68F50, Q6GMH3, Q6IBS0, Q759P0, Q7QG28, Q7ZXP0, Q869T1, Q91YR1, Q96VU9, Q9VFM9, Q9Z0P5, O15902, O49606, P0CM06, P0CM07, P0DJ26

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	GMFB	phosphorylation
PRKACA	“up-regulates activity”	GMFB	phosphorylation
CSNK2A1	unknown	GMFB	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564130	GRCh37/hg19 14q22.2(chr14:54250363-55362006)x1	Pathogenic

SpliceAI

881 predictions. Top by Δscore:

Variant	Effect	Δscore
14:54482201:CA:C	acceptor_gain	1.0000
14:54482203:C:CC	acceptor_gain	1.0000
14:54483666:CTTA:C	donor_loss	1.0000
14:54483667:TTACT:T	donor_loss	1.0000
14:54483668:TA:T	donor_loss	1.0000
14:54483669:A:AC	donor_gain	1.0000
14:54483669:AC:A	donor_loss	1.0000
14:54483670:C:CA	donor_gain	1.0000
14:54483670:CTT:C	donor_gain	1.0000
14:54483673:A:AC	donor_gain	1.0000
14:54483674:T:C	donor_gain	1.0000
14:54483763:TCACT:T	acceptor_gain	1.0000
14:54483764:CACT:C	acceptor_gain	1.0000
14:54483764:CACTC:C	acceptor_gain	1.0000
14:54483765:ACT:A	acceptor_gain	1.0000
14:54483766:CT:C	acceptor_gain	1.0000
14:54483766:CTCTA:C	acceptor_gain	1.0000
14:54483767:TCT:T	acceptor_gain	1.0000
14:54483768:C:A	acceptor_gain	1.0000
14:54483768:C:CC	acceptor_gain	1.0000
14:54483770:A:C	acceptor_gain	1.0000
14:54488921:TCA:T	donor_loss	1.0000
14:54488922:CA:C	donor_loss	1.0000
14:54488923:A:AT	donor_loss	1.0000
14:54488924:C:CA	donor_loss	1.0000
14:54478112:A:AC	donor_gain	0.9900
14:54478113:C:CC	donor_gain	0.9900
14:54478117:A:C	donor_gain	0.9900
14:54479822:A:AC	donor_gain	0.9900
14:54479823:C:CC	donor_gain	0.9900

AlphaMissense

937 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:54479822:A:C	S107R	0.999
14:54479822:A:T	S107R	0.999
14:54479824:T:G	S107R	0.999
14:54479826:C:T	G106E	0.999
14:54479829:G:T	A105D	0.999
14:54483679:G:T	A31D	0.999
14:54478116:A:G	L134S	0.998
14:54478131:A:G	L129P	0.998
14:54479838:A:G	M102T	0.998
14:54479838:A:T	M102K	0.998
14:54480891:A:T	I89N	0.998
14:54480914:T:A	R81S	0.998
14:54480914:T:G	R81S	0.998
14:54480953:G:C	F68L	0.998
14:54480953:G:T	F68L	0.998
14:54480954:A:G	F68S	0.998
14:54480955:A:G	F68L	0.998
14:54481412:G:T	P66H	0.998
14:54481439:A:G	L57P	0.998
14:54483680:C:G	A31P	0.998
14:54479808:A:T	V112D	0.997
14:54479811:A:G	L111P	0.997
14:54479830:C:G	A105P	0.997
14:54479833:A:C	Y104D	0.997
14:54480881:A:C	S92R	0.997
14:54480881:A:T	S92R	0.997
14:54480883:T:G	S92R	0.997
14:54480887:G:C	F90L	0.997
14:54480887:G:T	F90L	0.997
14:54480889:A:G	F90L	0.997

dbSNP variants (sampled 300 via entrez): RS1000039405 (14:54481856 G>C), RS1000330546 (14:54488858 A>C,G), RS1000663585 (14:54490121 C>T), RS1000916542 (14:54477551 A>C), RS1000966883 (14:54477814 A>G), RS1001532481 (14:54481303 G>A), RS1001555804 (14:54480753 C>A,T), RS1001579522 (14:54474143 A>G), RS1001752639 (14:54487347 C>G,T), RS1001798266 (14:54482736 T>C), RS1001891290 (14:54482506 T>C), RS1001914979 (14:54475769 A>C), RS1001983290 (14:54481737 T>A,C), RS1002264940 (14:54483035 C>G), RS1002576775 (14:54479148 A>G)

Disease associations

OMIM: gene MIM:601713 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001786_22	Dental caries	2.000000e-07
GCST001786_33	Dental caries	2.000000e-06
GCST003477_3	Monobrow thickness	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	3
Air Pollutants	affects expression, increases abundance, decreases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
bisphenol A	decreases methylation, decreases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
beta-lapachone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

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