GMFG

Summary

GMFG (glia maturation factor gamma, HGNC:4374) is a protein-coding gene on chromosome 19q13.2, encoding Glia maturation factor gamma (O60234).

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 be located in extracellular region; ficolin-1-rich granule lumen; and secretory granule lumen. Predicted to be active in cortical actin cytoskeleton.

Source: NCBI Gene 9535 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 29 total
• Druggable target: yes
• MANE Select transcript: NM_004877

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4374
Approved symbol	GMFG
Name	glia maturation factor gamma
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000130755
Ensembl biotype	protein_coding
OMIM	604104
Entrez	9535

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000253054, ENST00000594700, ENST00000595207, ENST00000595636, ENST00000596583, ENST00000597595, ENST00000598034, ENST00000598218, ENST00000600322, ENST00000601387, ENST00000601731, ENST00000602185, ENST00000904715, ENST00000968994

RefSeq mRNA: 3 — MANE Select: NM_004877 NM_001301008, NM_001411106, NM_004877

CCDS: CCDS12532, CCDS74364, CCDS92613

Canonical transcript exons

ENST00000597595 — 7 exons

Exon	Start	End
ENSE00003065455	39335974	39336043
ENSE00003183432	39328359	39328548
ENSE00003509014	39333077	39333126
ENSE00003587682	39335435	39335531
ENSE00003590849	39329544	39329626
ENSE00003624091	39335261	39335310
ENSE00003644736	39329000	39329073

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 99.59.

FANTOM5 (CAGE): breadth broad, TPM avg 51.3502 / max 1727.8254, expressed in 863 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180854	50.6917	861
180852	0.6585	151

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.59	gold quality
leukocyte	CL:0000738	99.54	gold quality
mononuclear cell	CL:0000842	99.54	gold quality
granulocyte	CL:0000094	99.47	gold quality
bone marrow	UBERON:0002371	99.22	gold quality
spleen	UBERON:0002106	99.11	gold quality
blood	UBERON:0000178	99.05	gold quality
bone marrow cell	CL:0002092	98.81	gold quality
trabecular bone tissue	UBERON:0002483	98.81	gold quality
right lung	UBERON:0002167	98.74	gold quality
lymph node	UBERON:0000029	98.25	gold quality
periodontal ligament	UBERON:0008266	98.11	gold quality
upper lobe of left lung	UBERON:0008952	97.70	gold quality
vermiform appendix	UBERON:0001154	97.57	gold quality
omental fat pad	UBERON:0010414	97.36	gold quality
peritoneum	UBERON:0002358	97.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.14	gold quality
thymus	UBERON:0002370	97.01	gold quality
upper lobe of lung	UBERON:0008948	96.97	gold quality
gall bladder	UBERON:0002110	96.59	gold quality
tendon of biceps brachii	UBERON:0008188	95.72	gold quality
rectum	UBERON:0001052	95.19	gold quality
colonic epithelium	UBERON:0000397	94.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.65	gold quality
adipose tissue	UBERON:0001013	94.54	gold quality
caecum	UBERON:0001153	94.29	gold quality
connective tissue	UBERON:0002384	94.11	gold quality
lung	UBERON:0002048	93.61	gold quality
right lobe of thyroid gland	UBERON:0001119	93.27	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1302.81
E-MTAB-10662	yes	630.67
E-GEOD-130473	yes	143.99
E-MTAB-6701	yes	88.33
E-HCAD-1	yes	81.25
E-HCAD-4	yes	49.35
E-HCAD-10	yes	43.31
E-MTAB-8142	yes	37.97
E-MTAB-10287	yes	36.41
E-CURD-122	yes	34.71
E-CURD-88	yes	33.06
E-MTAB-8410	yes	31.19
E-GEOD-134144	yes	27.87
E-CURD-46	yes	22.36
E-MTAB-10042	yes	16.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting GMFG, 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-4282	99.99	75.36	6408
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-9900	96.06	65.48	557

Literature-anchored findings (GeneRIF, showing 13)

• characterized the promoter region and found the putative cis-acting regulatory elements responsible for promoter activity (PMID:12591611)
• GMFG is a hematopoietic-specific protein that may mediate the pluripotentiality and lineage commitment of human hematopoietic stem cells (PMID:17127212)
• regulates the migration and adherence of human T lymphocytes (PMID:22510515)
• our findings suggest that GMFG functions as a negative regulator of TLR4 signaling by facilitating TLR4 endocytic trafficking in macrophages (PMID:23677465)
• Together, the results suggest that GMFG functions by a mechanism similar to that of other ADF/cofilin family members, displaying a preference for ADP-Arp2/3 complex and undergoing inhibition by phosphorylation of a serine residue near the N terminus. (PMID:23897816)
• In this study, knockdown of GMF-gamma by RNA interference enhanced actin polymerization and contraction in human airway smooth muscle (HASM) cells and tissues without affecting myosin phosphorylation. (PMID:24818551)
• These results indicate that the effects of GMFG on monocyte migration and adhesion probably occur through preventing ubiquitin-mediated proteasome degradation of alpha5beta1-integrin and facilitating effective beta1-integrin recycling back to the plasma membrane. (PMID:26895964)
• High GMF-GAMMA expression is associated with colorectal cancer metastasis. (PMID:28075454)
• GMFgamma phosphorylation by c-Abl has an important role in coordinating lamellipodial and focal adhesion dynamics to regulate cell migration (PMID:30811945)
• Bioinformatics and survival analysis of glia maturation factor-gamma in pan-cancers. (PMID:33863293)
• RNF144A exerts tumor suppressor function in breast cancer through targeting YY1 for proteasomal degradation to downregulate GMFG expression. (PMID:35103856)
• GMFG (glia maturation factor gamma) inhibits lung cancer growth by activating p53 signaling pathway. (PMID:35383531)
• High Level of GMFG Correlated to Poor Clinical Outcome and Promoted Cell Migration and Invasion through EMT Pathway in Triple-Negative Breast Cancer. (PMID:37372337)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gmfg	ENSMUSG00000060791
rattus_norvegicus	Gmfg	ENSRNOG00000019838
drosophila_melanogaster	GMF	FBGN0028894
caenorhabditis_elegans		WBGENE00021758

Paralogs (1): GMFB (ENSG00000197045)

Protein

Protein identifiers

Glia maturation factor gamma — O60234 (reviewed: O60234)

All UniProt accessions (9): O60234, M0QX47, M0QXC2, M0QXZ6, M0QYG8, M0QYJ8, M0R0C1, M0R1D2, M0R2P2

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed predominantly in lung, heart and placenta.

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

RefSeq proteins (3): NP_001287937, NP_001398035, NP_004868* (*=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 (18 total): strand 6, helix 5, sequence variant 2, initiator methionine 1, chain 1, domain 1, modified residue 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3L50	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60234-F1	94.33	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

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 298 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_BNIP2, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOCC_SECRETORY_GRANULE, MODULE_45, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOMF_GROWTH_FACTOR_ACTIVITY, TGACCTY_ERR1_Q2, TANG_SENESCENCE_TP53_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, MODULE_75, GNF2_ICAM3, ROZANOV_MMP14_TARGETS_UP

GO Biological Process (4): protein phosphorylation (GO:0006468), 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 (7): extracellular region (GO:0005576), cortical actin cytoskeleton (GO:0030864), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813), nucleus (GO:0005634), cytoplasm (GO:0005737), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phosphorylation	1
protein modification process	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
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GMFG	ACTR2	P61160	660
GMFG	TWF2	Q6IBS0	560
GMFG	TWF1	Q12792	516
GMFG	WASF2	Q9Y6W5	491
GMFG	CFL2	Q9Y281	470
GMFG	CFL1	P23528	470
GMFG	ECD	O95905	455
GMFG	WDR1	O75083	408
GMFG	DBNL	P84070	402
GMFG	ARPIN	Q7Z6K5	388
GMFG	A0A0A6YYH1	A0A0A6YYH1	384
GMFG	DBN1	Q16643	383
GMFG	RPS20	P17075	377
GMFG	Q32Q12	Q32Q12	352
GMFG	CORO1A	P31146	351

IntAct

14 interactions, top by confidence:

A	B	Type	Score
GMFB	GMFG	psi-mi:“MI:0914”(association)	0.530
GMFG	PRUNE1	psi-mi:“MI:0914”(association)	0.530
CAMK1D	GMFG	psi-mi:“MI:0915”(physical association)	0.370
GMFG	VANGL1	psi-mi:“MI:0915”(physical association)	0.370
GMFG	HSPA14	psi-mi:“MI:0914”(association)	0.350
SPATA8	GMFG	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
GMFG	CLSTN1	psi-mi:“MI:0914”(association)	0.350
GMFB	RIPK2	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
	GMFG	psi-mi:“MI:0915”(physical association)	0.000
GMFG	PSD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): GMFG (Affinity Capture-MS), PRUNE (Affinity Capture-MS), LANCL2 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), GMFG (Affinity Capture-MS), GMFG (Affinity Capture-MS), VAT1 (Affinity Capture-MS), PRUNE (Affinity Capture-MS), GMFG (Affinity Capture-MS), LANCL2 (Affinity Capture-MS), FN3K (Affinity Capture-MS), GMFG (Affinity Capture-MS), CLSTN1 (Affinity Capture-MS), GMFG (Affinity Capture-MS), GMFG (Protein-peptide)

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ABL1	“down-regulates activity”	GMFG	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

902 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39329039:C:CA	donor_gain	1.0000
19:39329516:T:A	donor_gain	1.0000
19:39335433:A:AC	donor_gain	1.0000
19:39335434:C:CC	donor_gain	1.0000
19:39335532:C:CC	acceptor_gain	1.0000
19:39336000:T:TA	donor_gain	1.0000
19:39329547:CAGGG:C	donor_gain	0.9900
19:39333123:TGTT:T	acceptor_gain	0.9900
19:39333127:C:CC	acceptor_gain	0.9900
19:39333133:C:CT	acceptor_gain	0.9900
19:39333134:A:T	acceptor_gain	0.9900
19:39333141:C:CT	acceptor_gain	0.9900
19:39335271:T:TA	donor_gain	0.9900
19:39335311:C:CC	acceptor_gain	0.9900
19:39335434:CTT:C	donor_gain	0.9900
19:39335527:TCAGA:T	acceptor_gain	0.9900
19:39335528:CAGA:C	acceptor_gain	0.9900
19:39335528:CAGAC:C	acceptor_gain	0.9900
19:39335530:GA:G	acceptor_gain	0.9900
19:39335950:C:A	donor_gain	0.9900
19:39329026:G:A	donor_gain	0.9800
19:39329543:CCCA:C	donor_gain	0.9800
19:39333071:GGATA:G	donor_loss	0.9800
19:39333072:GATAC:G	donor_loss	0.9800
19:39333073:ATACC:A	donor_loss	0.9800
19:39333074:TACCT:T	donor_loss	0.9800
19:39333075:A:AG	donor_loss	0.9800
19:39333126:TC:T	acceptor_loss	0.9800
19:39333127:C:CA	acceptor_loss	0.9800
19:39333128:T:A	acceptor_loss	0.9800

AlphaMissense

947 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39329036:A:C	S107R	0.999
19:39329036:A:T	S107R	0.999
19:39329038:T:G	S107R	0.999
19:39335443:G:T	A31D	0.999
19:39329040:C:T	G106E	0.998
19:39329047:A:C	Y104D	0.998
19:39329052:A:G	M102T	0.998
19:39329052:A:T	M102K	0.998
19:39329561:A:T	I89N	0.998
19:39328505:A:G	L134P	0.997
19:39329025:A:G	L111P	0.997
19:39329033:T:A	K108N	0.997
19:39329033:T:G	K108N	0.997
19:39329043:G:T	A105E	0.997
19:39329568:A:G	C87R	0.997
19:39329585:C:G	R81P	0.997
19:39329618:A:T	V70D	0.997
19:39329623:G:C	F68L	0.997
19:39329623:G:T	F68L	0.997
19:39329624:A:G	F68S	0.997
19:39329625:A:G	F68L	0.997
19:39333080:G:T	P66H	0.997
19:39333107:A:G	L57P	0.997
19:39335444:C:G	A31P	0.997
19:39335482:A:G	L18P	0.997
19:39328520:A:G	L129P	0.996
19:39329000:C:A	K119N	0.996
19:39329000:C:G	K119N	0.996
19:39329551:G:C	S92R	0.996
19:39329551:G:T	S92R	0.996

dbSNP variants (sampled 300 via entrez): RS1000131960 (19:39328320 A>C), RS1000183909 (19:39333766 G>T), RS1000257006 (19:39334831 A>C), RS1000286575 (19:39335000 C>A), RS1000425457 (19:39333484 G>A), RS1000701308 (19:39334514 T>A,C), RS1000754965 (19:39334855 T>A,C), RS1001028358 (19:39328748 G>A,C), RS1001139553 (19:39330426 CT>C,CTT,CTTT), RS1001574921 (19:39329421 C>G), RS1001796225 (19:39335374 C>T), RS1002298182 (19:39330107 T>C), RS1002499201 (19:39331026 C>G), RS1002636432 (19:39330711 C>T), RS1002756766 (19:39337179 G>A)

Disease associations

OMIM: gene MIM:604104 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004744_53	Lung adenocarcinoma	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067026 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.63	Kd	2.354	nM	CHEMBL5653589
8.54	ED50	2.907	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148439: Binding affinity to human GMFG incubated for 45 mins by Kinobead based pull down assay	kd	0.0024	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases expression	2
triphenyl phosphate	affects expression	1
terbufos	decreases methylation	1
beta-lapachone	decreases expression	1
butyraldehyde	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	increases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Fonofos	decreases methylation	1
Ivermectin	decreases expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Parathion	decreases methylation	1
Quercetin	increases expression	1
Silicon Dioxide	increases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651481	Binding	Binding affinity to human GMFG incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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