GBF1

Summary

GBF1 (golgi brefeldin A resistant guanine nucleotide exchange factor 1, HGNC:4181) is a protein-coding gene on chromosome 10q24.32, encoding Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (Q92538). Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP wi…. It is a common-essential gene (DepMap: required in 98.4% of cancer cell lines).

This gene encodes a member of the Sec7 domain family. The encoded protein is a guanine nucleotide exchange factor that regulates the recruitment of proteins to membranes by mediating GDP to GTP exchange. The encoded protein is localized to the Golgi apparatus and plays a role in vesicular trafficking by activating ADP ribosylation factor 1. The encoded protein has also been identified as an important host factor for viral replication. Multiple transcript variants have been observed for this gene.

Source: NCBI Gene 8729 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth Disease, axonal, type 2GG (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 18
• Clinical variants (ClinVar): 409 total — 2 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 23
• Cancer dependency (DepMap): dependent in 98.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_001377137

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4181
Approved symbol	GBF1
Name	golgi brefeldin A resistant guanine nucleotide exchange factor 1
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0248, ARF1GEF
Ensembl gene	ENSG00000107862
Ensembl biotype	protein_coding
OMIM	603698
Entrez	8729

Gene structure

Transcript identifiers

Ensembl transcripts: 126 — 48 protein_coding, 48 nonsense_mediated_decay, 18 protein_coding_CDS_not_defined, 12 retained_intron

ENST00000369983, ENST00000476019, ENST00000673650, ENST00000674034, ENST00000676474, ENST00000676482, ENST00000676513, ENST00000676558, ENST00000676560, ENST00000676561, ENST00000676606, ENST00000676673, ENST00000676682, ENST00000676735, ENST00000676802, ENST00000676807, ENST00000676854, ENST00000676861, ENST00000676877, ENST00000676900, ENST00000676927, ENST00000676934, ENST00000676939, ENST00000676985, ENST00000676993, ENST00000677017, ENST00000677098, ENST00000677100, ENST00000677235, ENST00000677240, ENST00000677247, ENST00000677269, ENST00000677431, ENST00000677439, ENST00000677461, ENST00000677487, ENST00000677491, ENST00000677504, ENST00000677506, ENST00000677522, ENST00000677607, ENST00000677618, ENST00000677627, ENST00000677629, ENST00000677642, ENST00000677655, ENST00000677662, ENST00000677683, ENST00000677719, ENST00000677776, ENST00000677797, ENST00000677811, ENST00000677838, ENST00000677842, ENST00000677852, ENST00000677871, ENST00000677917, ENST00000677947, ENST00000677956, ENST00000677975, ENST00000678007, ENST00000678014, ENST00000678036, ENST00000678126, ENST00000678127, ENST00000678157, ENST00000678215, ENST00000678222, ENST00000678268, ENST00000678292, ENST00000678293, ENST00000678319, ENST00000678344, ENST00000678351, ENST00000678401, ENST00000678417, ENST00000678426, ENST00000678453, ENST00000678476, ENST00000678486, ENST00000678504, ENST00000678514, ENST00000678527, ENST00000678530, ENST00000678558, ENST00000678571, ENST00000678575, ENST00000678585, ENST00000678604, ENST00000678665, ENST00000678666, ENST00000678722, ENST00000678742, ENST00000678767, ENST00000678806, ENST00000678826, ENST00000678840, ENST00000678923, ENST00000678924, ENST00000678941, ENST00000679003, ENST00000679013, ENST00000679040, ENST00000679080, ENST00000679084, ENST00000679087, ENST00000679093, ENST00000679139, ENST00000679155, ENST00000679186, ENST00000679203, ENST00000679238, ENST00000679253, ENST00000679280, ENST00000679288, ENST00000679298, ENST00000679305, ENST00000679317, ENST00000871604, ENST00000871605, ENST00000871606, ENST00000871607, ENST00000871608, ENST00000916344, ENST00000916345, ENST00000965494

RefSeq mRNA: 20 — MANE Select: NM_001377137 NM_001199378, NM_001199379, NM_001377137, NM_001377138, NM_001377139, NM_001377140, NM_001377141, NM_001391922, NM_001391923, NM_001391924, NM_001391925, NM_001391926, NM_001391927, NM_001391928, NM_001391929, NM_001391930, NM_001391931, NM_001411003, NM_001411027, NM_004193

CCDS: CCDS7533, CCDS91328, CCDS91329, CCDS91330, CCDS91331, CCDS91332, CCDS91333, CCDS91334, CCDS91335, CCDS91336

Canonical transcript exons

ENST00000369983 — 40 exons

Exon	Start	End
ENSE00000722583	102344051	102344182
ENSE00000722587	102351843	102351951
ENSE00000722599	102358039	102358186
ENSE00000722602	102358506	102358729
ENSE00000722612	102360184	102360395
ENSE00000722616	102361022	102361120
ENSE00000722619	102361718	102361912
ENSE00000722622	102362475	102362664
ENSE00000722626	102363256	102363396
ENSE00000722630	102363710	102363798
ENSE00000722634	102365397	102365599
ENSE00000722639	102366383	102366506
ENSE00000722644	102367085	102367210
ENSE00000722647	102367478	102367560
ENSE00000722651	102368218	102368454
ENSE00000722653	102368739	102368832
ENSE00000722654	102369211	102369387
ENSE00000722655	102369711	102369775
ENSE00000722657	102369861	102369984
ENSE00000722658	102370174	102370245
ENSE00000722659	102370384	102370478
ENSE00000722660	102370707	102370860
ENSE00000722662	102375359	102375584
ENSE00000722663	102376272	102376432
ENSE00000722665	102376560	102376800
ENSE00000722669	102376935	102377140
ENSE00000722673	102379284	102379434
ENSE00000722677	102379521	102379651
ENSE00000722682	102379853	102379954
ENSE00000722687	102380249	102380362
ENSE00000722690	102380506	102380686
ENSE00000722693	102381127	102381255
ENSE00000811504	102351256	102351374
ENSE00001026428	102352458	102352518
ENSE00001100976	102260050	102260116
ENSE00001136564	102353600	102353654
ENSE00001451422	102258929	102259034
ENSE00001451424	102245532	102245781
ENSE00003904487	102359267	102359435
ENSE00003936997	102382056	102382896

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.8629 / max 438.0609, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106694	58.6582	1823
106695	0.2047	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	98.95	gold quality
ventricular zone	UBERON:0003053	98.17	gold quality
adenohypophysis	UBERON:0002196	98.04	gold quality
sural nerve	UBERON:0015488	97.76	gold quality
stromal cell of endometrium	CL:0002255	97.54	gold quality
right lobe of thyroid gland	UBERON:0001119	97.24	gold quality
ganglionic eminence	UBERON:0004023	97.24	gold quality
apex of heart	UBERON:0002098	97.17	gold quality
cortical plate	UBERON:0005343	97.07	gold quality
mucosa of transverse colon	UBERON:0004991	96.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.80	gold quality
left lobe of thyroid gland	UBERON:0001120	96.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.64	gold quality
pituitary gland	UBERON:0000007	96.52	gold quality
cerebellar hemisphere	UBERON:0002245	96.42	gold quality
adrenal tissue	UBERON:0018303	96.35	gold quality
cerebellar cortex	UBERON:0002129	96.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.24	gold quality
metanephros cortex	UBERON:0010533	96.14	gold quality
right uterine tube	UBERON:0001302	96.07	gold quality
right frontal lobe	UBERON:0002810	96.07	gold quality
transverse colon	UBERON:0001157	96.02	gold quality
granulocyte	CL:0000094	96.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.83	gold quality
right lobe of liver	UBERON:0001114	95.80	gold quality
left testis	UBERON:0004533	95.77	gold quality
minor salivary gland	UBERON:0001830	95.75	gold quality
lower esophagus mucosa	UBERON:0035834	95.72	gold quality
skin of leg	UBERON:0001511	95.71	gold quality
skin of abdomen	UBERON:0001416	95.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-76312	yes	105.67
E-ANND-3	yes	9.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting GBF1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-130A-5P	99.33	70.26	2623

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• detailed subcellular localization to the cis-Golgi (PMID:12047556)
• novel interaction between p115 and Golgi-specific brefeldin-A-resistant factor 1 (GBF1) (PMID:12634853)
• characterization of alternatively spliced and truncated forms of GBF1 defines regions important for activity (PMID:12646181)
• an Arf1-GBF1-Brefeldin A complex is formed and has a longer residence time on Golgi membranes than GBF1 or Arf1 alone (PMID:15616190)
• A continuous cycle of recruitment and dissociation of GBF1 to membranes is required for sustained ARF activation and COP I recruitment that underlies ER-Golgi traffic. (PMID:15813748)
• GBF1 is recruited to the endogenous IRF-9 promoter, and interacts with C/EBP-beta, IL-1, and IL-6 (PMID:16318580)
• These observations strongly suggest that GBF1 regulates COPI membrane recruitment in the early secretory pathway. (PMID:16926190)
• Two different poliovirus proteins independently recruit different Arf GEFs (GBF1 and BIG1/2) to membranes as part of cellular pathways utilized by the virus to form its membranous replication complex. (PMID:17079330)
• analysis of the binding domain in GBF1 showed that the extreme N terminus, the dimerization/cyclophilin binding domain, and the homology upstream of Sec7 domain are required for the interaction with coxsackievirus protein 3A (PMID:17329336)
• These data support a model where Rab1b-GTP induces GBF1 recruitment at the ERES interface and at the Golgi complex where it is required for COPII/COPI exchange or COPI vesicle formation, respectively. (PMID:17429068)
• Required for GGA adaptor protein recruitment to Golgi membranes; plays a role in the proper processing and sorting of lysosomal cargo. (PMID:17666033)
• These findings suggest that a secretory pathway capable of trafficking soluble proteins can be maintained in cells in which COPI recruitment is compromised by GBF1 depletion. (PMID:17956946)
• COPII is the only coat required for sorting and export from the endoplasmic reticulum exit sites, whereas GBF1, but not BIGs, is required for COPI recruitment, Golgi subcompartmentalization, and cargo progression to the cell surface. (PMID:18003980)
• GBF1 is a AMPK substrate and AMPK-mediated phosphorylation of GBF1 at Thr(1337) has a critical role, presumably by attenuating function of GBF1, in disassembly of the Golgi apparatus induced under stress conditions that lower the intracellular ATP (PMID:18063581)
• Unfolded protein response and cell death after depletion of brefeldin A-inhibited guanine nucleotide-exchange protein GBF1. (PMID:18287014)
• GDP-bound class II Arfs associate with the ER-Golgi intermediate compartment independently of GBF1 (PMID:18524849)
• siRNAs demonstrate that GBF1-mediated ARF1 activation is required for efficient MHV RNA replication (PMID:18551169)
• AG1478 inhibits GBF1, a large nucleotide exchange factor for the ADP-ribosylation factor, in a Sec7 domain-dependent manner and mimics the phenotype of a GBF1 mutant that has an inactive mutation (PMID:18799457)
• GBF1 is responsible for the sensitivity of poliovirus infection to BFA, and is required for virus replication (PMID:19023417)
• crucial for coxsackievirus B3 RNA replication (PMID:19740986)
• GBF1 is a cellular factor required for HCV infection. (PMID:19906930)
• The authors demonstrate that Rab1b-activated GBF1 and ARF1 are involved in Ebolavirus virion formation, suggesting that both the COPII and COPI transport systems play a role in Ebolavirus VP40-mediated particle formation. (PMID:20164217)
• Data propose that the phosphorylation and membrane dissociation of GBF1 and the consequent reduction in ARF-GTP levels in mitosis are important for changes in Golgi dynamics (PMID:20175751)
• The brefeldin A block of poliovirus replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. (PMID:20497182)
• Data suggest that Rab1 contributes to the specificity and timing of GBF1 recruitment by activating PI4KIIIalpha, and that the PtdIns(4)P produced then allows GBF1 to bind to Golgi membranes and activate Arf1. (PMID:20530568)
• Both human and canine GBF1 can be inhibited by compound LG186, a small molecule derived from Exo2, a small molecule inhibitor of secretion and Shiga toxin cytotoxicity. (PMID:20854417)
• The COG (conserved oligomeric Golgi) complex plays a role in the localization, but not membrane association of GBF1. (PMID:21722633)
• GBF1 and ATGL interact directly and in cells, through multiple contact sites on each protein. (PMID:21789191)
• We hypothesize that sphingomyelin acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by GBF1-dependent pathway is essential for inclusion growth and stability. (PMID:21909260)
• The GBF1 participated in delivery of adipose triglyceride lipase (ATGL) onto the lipid droplets(LD) surface (PMID:22185782)
• the vesicular transport proteins ARF1 and GBF1 colocalized with PI4KIIIbeta and were both required for HCV replication (PMID:22359663)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• GBF1-mediated Arf1 activation is necessary to unify cell polarity during chemotaxis (PMID:22573891)
• an early acting GEF (GBF1) activates ARFs that mediate recruitment of late acting GEFs (BIG1/2) to coordinate coating events within the pre-Golgi/Golgi/TGN continuum. (PMID:23386609)
• These data suggest that AMPK-GBF1-Arf1 signaling is involved in the regulation of Golgi fragmentation during mitosis. (PMID:23418352)
• Study provides evidence that GBF-1 is required in endoplasmic reticulum structure and endosomal traffic. (PMID:23840591)
• GBF1 causes increased Arf-GTP production at the Golgi, consistent with a feed-forward self-limiting mechanism of Arf activation. (PMID:24213530)
• GBF1 plays a critical role early in dengue infection that is independent of its role in the maintenance of Golgi structure. (PMID:24855065)
• Although human rhinovirus 3A protein was previously shown to interact with ACBD3, these data suggest that PI4KIIIbeta recruitment occurred independently of both GBF1 and ACBD3. (PMID:25410869)
• The role of GBF1 in poliovirus replication is independent of its Arf activating function. (PMID:25653442)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	gbf1	ENSDARG00000027016
mus_musculus	Gbf1	ENSMUSG00000025224
rattus_norvegicus	Gbf1	ENSRNOG00000026048
drosophila_melanogaster	siz	FBGN0026179
drosophila_melanogaster	Sec71	FBGN0028538
drosophila_melanogaster	garz	FBGN0264560
caenorhabditis_elegans		WBGENE00007703
caenorhabditis_elegans		WBGENE00008685
caenorhabditis_elegans	agef-1	WBGENE00012386

Paralogs (15): CYTH3 (ENSG00000008256), PSD (ENSG00000059915), MON2 (ENSG00000061987), ARFGEF1 (ENSG00000066777), CYTH4 (ENSG00000100055), CYTH2 (ENSG00000105443), CYTH1 (ENSG00000108669), IQSEC3 (ENSG00000120645), ARFGEF2 (ENSG00000124198), IQSEC2 (ENSG00000124313), PSD4 (ENSG00000125637), IQSEC1 (ENSG00000144711), PSD2 (ENSG00000146005), PSD3 (ENSG00000156011), FBXO8 (ENSG00000164117)

Protein

Protein identifiers

Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 — Q92538 (reviewed: Q92538)

All UniProt accessions (84): Q92538, A0A669KB10, A0A669KBG8, A0A7I2V2F8, A0A7I2V2G6, A0A7I2V2I0, A0A7I2V2L1, A0A7I2V2L4, A0A7I2V2L5, A0A7I2V2Q1, A0A7I2V2Q5, A0A7I2V2Q6, A0A7I2V2U1, A0A7I2V2Y7, A0A7I2V2Z8, A0A7I2V300, A0A7I2V305, A0A7I2V306, A0A7I2V329, A0A7I2V336, A0A7I2V338, A0A7I2V342, A0A7I2V350, A0A7I2V3A8, A0A7I2V3B1, A0A7I2V3E5, A0A7I2V3H2, A0A7I2V3J0, A0A7I2V3Q4, A0A7I2V3R2, A0A7I2V3S0, A0A7I2V3Y5, A0A7I2V3Y7, A0A7I2V452, A0A7I2V470, A0A7I2V489, A0A7I2V4E0, A0A7I2V4F1, A0A7I2V4F9, A0A7I2V4H1, A0A7I2V4K2, A0A7I2V4L8, A0A7I2V4M3, A0A7I2V4M6, A0A7I2V4N5, A0A7I2V4N7, A0A7I2V4Q7, A0A7I2V4V3, A0A7I2V4V8, A0A7I2V4W6, A0A7I2V4X4, A0A7I2V4Z4, A0A7I2V514, A0A7I2V528, A0A7I2V529, A0A7I2V541, A0A7I2V578, A0A7I2V5C9, A0A7I2V5I9, A0A7I2V5S3, A0A7I2V5T8, A0A7I2V5V9, A0A7I2V5W2, A0A7I2V5Z1, A0A7I2V5Z2, A0A7I2V622, A0A7I2V662, A0A7I2V6D0, A0A7I2V6G3, A0A7I2YQ62, A0A7I2YQ65, A0A7I2YQ79, A0A7I2YQA6, A0A7I2YQB8, A0A7I2YQC3, A0A7I2YQC6, A0A7I2YQD3, A0A7I2YQE0, A0A7I2YQJ5, A0A7I2YQM0, A0A7I2YQM2, A0A7I2YQN3, A0A7I2YQN6, A0A7I2YQP6

UniProt curated annotations — full annotation on UniProt →

Function. Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP with GTP. Recruitment to cis-Golgi membranes requires membrane association of Arf-GDP and can be regulated by ARF1, ARF3, ARF4 and ARF5. Involved in the recruitment of the COPI coat complex to the endoplasmic reticulum exit sites (ERES), and the endoplasmic reticulum-Golgi intermediate (ERGIC) and cis-Golgi compartments which implicates ARF1 activation. Involved in COPI vesicle-dependent retrograde transport from the ERGIC and cis-Golgi compartments to the endoplasmic reticulum (ER). Involved in the trans-Golgi network recruitment of GGA1, GGA2, GGA3, BIG1, BIG2, and the AP-1 adaptor protein complex related to chlathrin-dependent transport; the function requires its GEF activity (probably at least in part on ARF4 and ARF5). Has GEF activity towards ARF1. Has in vitro GEF activity towards ARF5. Involved in the processing of PSAP. Required for the assembly of the Golgi apparatus. The AMPK-phosphorylated form is involved in Golgi disassembly during mitotis and under stress conditions. May be involved in the COPI vesicle-dependent recruitment of PNPLA2 to lipid droplets; however, this function is under debate. In neutrophils, involved in G protein-coupled receptor (GPCR)-mediated chemotaxis und superoxide production. Proposed to be recruited by phosphatidylinositol-phosphates generated upon GPCR stimulation to the leading edge where it recruits and activates ARF1, and is involved in recruitment of GIT2 and the NADPH oxidase complex. Plays a role in maintaining mitochondrial morphology.

Subunit / interactions. Can form homodimers and probably homotetramers. Interacts with COPG1; the interaction is independent of ARF1 activation. Interacts with ARF1, ARF3, ARF4 and ARF5. Interacts with RAB1B (GTP-bound form); required for GBF1 membrane association. Interacts with GGA1, GGA2 and GGA3. Interacts with USO1. Interacts (via SEC7 domain) with PNPLA2 (via C-terminus); the interaction is direct. Interacts with ARMH3. (Microbial infection) Interacts with poliovirus protein 3A.

Subcellular location. Golgi apparatus. cis-Golgi network. Endoplasmic reticulum-Golgi intermediate compartment. trans-Golgi network. Cytoplasm. Lipid droplet. Membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. AMPK-mediated phosphorylation at Thr-1338 is induced by 2-deoxyglucose (2-DG) and AICA ribonucleotide, and occurs during mitosis leading to membrane disassociation and inactivation of ARF1 during mitosis.

Disease relevance. Charcot-Marie-Tooth disease, axonal, type 2GG (CMT2GG) [MIM:606483] An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2GG is an autosomal dominant form characterized by slowly progressive distal muscle weakness and atrophy primarily affecting the lower limbs and causing difficulty walking. Some individuals may also have involvement of the hands. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by brefeldin A (BFA). Inhibited by golgicide A (GCA).

Domain organisation. The DCB (dimerization and cyclophilin-binding) and HUS (homology upstream of Sec7) domains are necessary for dimerization. The DCB domain is proposed to support constitutive homodimerization; the HUS domain interacts with the DCB domain which may occur intramolecular or intermolecular.

Isoforms (4)

UniProt ID	Names	Canonical?
Q92538-4	1	yes
Q92538-1	4
Q92538-2	2
Q92538-3	3

RefSeq proteins (20): NP_001186307, NP_001186308, NP_001364066, NP_001364067, NP_001364068, NP_001364069, NP_001364070, NP_001378851, NP_001378852, NP_001378853, NP_001378854, NP_001378855, NP_001378856, NP_001378857, NP_001378858, NP_001378859, NP_001378860, NP_001397932, NP_001397956, NP_004184 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000904	Sec7_dom	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR023394	Sec7_C_sf	Homologous_superfamily
IPR032691	Mon2/Sec7/BIG1-like_HUS	Domain
IPR035999	Sec7_dom_sf	Homologous_superfamily
IPR056604	GBF1-like_TPR	Domain

Pfam: PF01369, PF12783, PF23325

UniProt features (52 total): modified residue 13, region of interest 11, compositionally biased region 10, sequence variant 5, mutagenesis site 5, sequence conflict 4, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92538-F1	71.42	0.37

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 (13): 350, 353, 508, 663, 1299, 1317, 1319, 1321, 1336, 1338, 1476, 1774, 1785

Mutagenesis-validated functional residues (5):

Position	Phenotype
544	increases interaction with copg1 and pnpla2.
795	inhibits golgi membrane recruitment of gga1, gga2 and gga3; generates misprocessing of psap.
795	arrests retrograde ergic/cis-golgi-to-er transport at an early step and causes disassembly of the golgi and disassociati
833	confers bfa tolerance.
1338	prevents 2-dg-induced golgi disassembly.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-5620916	VxPx cargo-targeting to cilium
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-9918476	Assembly and Release of Dengue Virus Virions
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 312 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_VESICLE_LOCALIZATION, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_VESICLE_ORGANIZATION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_TARGETING, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, YY1_Q6, EFC_Q6

GO Biological Process (25): cell activation involved in immune response (GO:0002263), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), post-Golgi vesicle-mediated transport (GO:0006892), Golgi to endosome transport (GO:0006895), Golgi organization (GO:0007030), regulation of mitotic cell cycle (GO:0007346), protein transport (GO:0015031), neutrophil chemotaxis (GO:0030593), regulation of ARF protein signal transduction (GO:0032012), protein localization to Golgi apparatus (GO:0034067), retrograde transport, endosome to Golgi (GO:0042147), COPI coating of Golgi vesicle (GO:0048205), cilium assembly (GO:0060271), establishment of monopolar cell polarity (GO:0061162), protein localization to endoplasmic reticulum exit site (GO:0070973), Golgi disassembly (GO:0090166), endoplasmic reticulum-Golgi intermediate compartment organization (GO:0097111), cellular response to virus (GO:0098586), reactive oxygen species biosynthetic process (GO:1903409), protein localization to endoplasmic reticulum tubular network (GO:1903420), regulation of protein localization to cell surface (GO:2000008), endomembrane system organization (GO:0010256), vesicle-mediated transport (GO:0016192), endosomal transport (GO:0016197)

GO Molecular Function (5): guanyl-nucleotide exchange factor activity (GO:0005085), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (15): Golgi membrane (GO:0000139), peroxisome (GO:0005777), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), cis-Golgi network (GO:0005801), trans-Golgi network (GO:0005802), lipid droplet (GO:0005811), cytosol (GO:0005829), membrane (GO:0016020), cell leading edge (GO:0031252), cytoplasm (GO:0005737), endomembrane system (GO:0012505), Golgi apparatus subcompartment (GO:0098791)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Dengue Virus Infection	2
Membrane Trafficking	1
Cargo trafficking to the periciliary membrane	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
intercellular transport	3
Golgi vesicle transport	3
Golgi apparatus	3
intracellular membrane-bounded organelle	3
cytosolic transport	2
organelle organization	2
phosphatidylinositol phosphate binding	2
binding	2
Golgi apparatus subcompartment	2
cell activation	1
immune effector process	1
immune response	1
intracellular transport	1
post-Golgi vesicle-mediated transport	1
endomembrane system organization	1
mitotic cell cycle	1
regulation of cell cycle	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
granulocyte chemotaxis	1
neutrophil migration	1
ARF protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
protein localization to organelle	1
endosomal transport	1
COPI-coated vesicle budding	1
Golgi transport vesicle coating	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
establishment of cell polarity	1
establishment or maintenance of monopolar cell polarity	1

Protein interactions and networks

STRING

1711 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GBF1	ARF1	P10947	796
GBF1	ARF6	P26438	739
GBF1	PI4KB	P78405	691
GBF1	RABIF	P47224	667
GBF1	CDKN2A	P42771	635
GBF1	RAB6A	P20340	614
GBF1	COPB1	P53618	562
GBF1	CIAO1	O76071	542
GBF1	RSAD2	Q8WXG1	535
GBF1	ARFGAP1	Q8N6T3	531
GBF1	ACBD3	Q9H3P7	529
GBF1	ARF4	P18085	520
GBF1	RAB1B	Q9H0U4	507
GBF1	ARFRP1	Q13795	490
GBF1	ARFGAP3	Q9NP61	488

IntAct

183 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
YWHAG	GBF1	psi-mi:“MI:0915”(physical association)	0.820
YWHAB	WDR62	psi-mi:“MI:0914”(association)	0.770
MILR1	INPPL1	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
IRS4	PIK3R2	psi-mi:“MI:0914”(association)	0.640
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
STK16	UNC119B	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
	GBF1	psi-mi:“MI:0914”(association)	0.500
GBF1		psi-mi:“MI:0915”(physical association)	0.500

BioGRID (542): GBF1 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), GBF1 (Co-fractionation), PUS7 (Co-fractionation), RBM26 (Co-fractionation), VARS (Co-fractionation), GBF1 (Affinity Capture-MS), GBF1 (Proximity Label-MS), GBF1 (Biochemical Activity), GBF1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5G2, A2AFR3, A7MBL8, B9EJ86, E1C1R4, E1C3P4, F1LXF1, O94806, O94967, P0C6S7, P0CAX5, P11274, P22682, Q0V9G5, Q14161, Q14CM0, Q15139, Q16513, Q1RMU2, Q3KR37, Q3LAC4, Q3UGM2, Q5RED8, Q5T6S3, Q5U252, Q62101, Q66H62, Q6DFZ1, Q6P5G6, Q6PAJ1, Q70Z35, Q7Z6G8, Q80TI0, Q80TQ2, Q80YA9, Q8BIZ1, Q8BWW9, Q8BY87, Q8K1Y2, Q8NEL9

Diamond homologs: A0A0G2JUG7, A2A5R2, A5PKW4, D4A631, E1JIT7, F1MUS9, F4IXW2, F4JN05, F4JSZ5, F4K2K3, G3X9K3, G5EET6, O08967, O13690, O13817, O43739, O46382, P11075, P34512, P39993, P47102, P63034, P63035, P97694, P97696, Q10491, Q15438, Q2KI41, Q2PFD7, Q3TES0, Q42510, Q54KA7, Q5DTT2, Q5DU25, Q5E9G6, Q5JU85, Q6DFZ1, Q6DN90, Q6P1I6, Q76M68

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PRKAA1	down-regulates	GBF1	phosphorylation
AMPK	down-regulates	GBF1	phosphorylation
CSNK2A1	“down-regulates quantity by destabilization”	GBF1	phosphorylation
SCF-betaTRCP	“down-regulates quantity by destabilization”	GBF1	ubiquitination
GBF1	“up-regulates activity”	ARF1	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 212 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
Activation of BAD and translocation to mitochondria	7	38.1×	5e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	33.6×	9e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	33.6×	9e-08
Activation of BH3-only proteins	7	24.8×	9e-07
RHO GTPases activate PKNs	8	18.1×	1e-06
Intrinsic Pathway for Apoptosis	8	16.7×	2e-06
Translocation of SLC2A4 (GLUT4) to the plasma membrane	12	13.2×	3e-08
DAP12 signaling	5	13.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	288
Likely benign	50
Benign	19

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1456216	NM_005029.4(PITX3):c.636_637dup (p.Gly213fs)	Pathogenic
468353	NM_005029.4(PITX3):c.640_656dup (p.Gly220fs)	Pathogenic
1675431	NM_001377137.1(GBF1):c.4384C>T (p.Arg1462Trp)	Likely pathogenic
372897	NM_005029.4(PITX3):c.646C>T (p.Gln216Ter)	Likely pathogenic
620191	NM_005029.4(PITX3):c.762C>A (p.Tyr254Ter)	Likely pathogenic
6938	NM_005029.4(PITX3):c.38G>A (p.Ser13Asn)	Likely pathogenic

SpliceAI

6285 predictions. Top by Δscore:

Variant	Effect	Δscore
10:102258925:GTA:G	acceptor_loss	1.0000
10:102258927:A:AG	acceptor_gain	1.0000
10:102258927:AG:A	acceptor_gain	1.0000
10:102258928:G:GG	acceptor_gain	1.0000
10:102258928:GG:G	acceptor_gain	1.0000
10:102258928:GGT:G	acceptor_gain	1.0000
10:102258928:GGTT:G	acceptor_gain	1.0000
10:102258928:GGTTT:G	acceptor_gain	1.0000
10:102259031:ACTGG:A	donor_loss	1.0000
10:102259032:CTGGT:C	donor_loss	1.0000
10:102259034:GGT:G	donor_loss	1.0000
10:102259035:G:GG	donor_gain	1.0000
10:102259035:GTA:G	donor_loss	1.0000
10:102259036:T:G	donor_loss	1.0000
10:102260037:ATGT:A	acceptor_gain	1.0000
10:102260038:T:G	acceptor_gain	1.0000
10:102260038:T:TA	acceptor_gain	1.0000
10:102260040:T:TA	acceptor_gain	1.0000
10:102260045:TACA:T	acceptor_loss	1.0000
10:102260046:A:AG	acceptor_gain	1.0000
10:102260046:ACAG:A	acceptor_gain	1.0000
10:102260047:C:G	acceptor_gain	1.0000
10:102260048:A:AG	acceptor_gain	1.0000
10:102260048:AG:A	acceptor_gain	1.0000
10:102260049:G:GA	acceptor_gain	1.0000
10:102260049:GG:G	acceptor_gain	1.0000
10:102260049:GGA:G	acceptor_gain	1.0000
10:102260049:GGAT:G	acceptor_gain	1.0000
10:102260095:G:GT	donor_gain	1.0000
10:102260114:CAG:C	donor_gain	1.0000

AlphaMissense

12179 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:102344107:T:C	S74P	1.000
10:102344123:G:A	G79D	1.000
10:102344141:C:A	A85E	1.000
10:102344144:T:A	L86H	1.000
10:102344144:T:C	L86P	1.000
10:102344153:T:A	V89D	1.000
10:102351303:G:C	A115P	1.000
10:102351307:T:A	V116D	1.000
10:102351316:C:A	A119D	1.000
10:102351321:T:C	F121L	1.000
10:102351322:T:C	F121S	1.000
10:102351322:T:G	F121C	1.000
10:102351323:T:A	F121L	1.000
10:102351323:T:G	F121L	1.000
10:102351345:G:C	D129H	1.000
10:102351355:T:A	V132D	1.000
10:102351358:T:C	L133P	1.000
10:102351370:T:C	L137P	1.000
10:102351847:T:C	L140P	1.000
10:102351856:T:C	L143P	1.000
10:102351873:G:C	G149R	1.000
10:102351874:G:A	G149D	1.000
10:102351883:T:C	L152P	1.000
10:102351920:C:G	C164W	1.000
10:102351925:G:C	R166P	1.000
10:102352464:T:G	L177W	1.000
10:102352475:G:C	A181P	1.000
10:102352488:T:A	L185H	1.000
10:102352488:T:C	L185P	1.000
10:102359411:T:C	F385L	1.000

dbSNP variants (sampled 300 via entrez): RS1000018555 (10:102337050 A>T), RS1000030706 (10:102358921 A>G), RS1000059136 (10:102288635 C>T), RS1000066281 (10:102289293 C>A), RS1000073720 (10:102336300 AAAAAAAAAAAAAAAG>A), RS1000086738 (10:102329670 A>G), RS1000098013 (10:102354631 T>C), RS1000107592 (10:102346311 G>A), RS1000131849 (10:102281256 C>T), RS1000138388 (10:102233605 G>A,C), RS1000189662 (10:102245839 T>A), RS1000189797 (10:102260741 T>C), RS1000191412 (10:102322116 T>A), RS1000217600 (10:102380040 A>G), RS1000269003 (10:102357704 A>C,T)

Disease associations

OMIM: gene MIM:603698 | disease phenotypes: MIM:107250, MIM:606483, MIM:610623, MIM:620378

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth Disease, axonal, type 2GG	Strong	Autosomal dominant
axonal neuropathy	Strong	Autosomal dominant

Mondo (5): anterior segment dysgenesis 1 (MONDO:0007138), Charcot-Marie-Tooth Disease, axonal, type 2GG (MONDO:0011675), cataract 11 multiple types (MONDO:0012527), Charcot-Marie-Tooth disease, dominant intermediate A (MONDO:0957273), axonal neuropathy (MONDO:0004183)

Orphanet (2): Autosomal dominant intermediate Charcot-Marie-Tooth disease type A (Orphanet:100043), Early onset non-syndromic cataract (Orphanet:91492)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001761	Pes cavus
HP:0001765	Hammertoe
HP:0002460	Distal muscle weakness
HP:0002936	Distal sensory impairment
HP:0003376	Steppage gait
HP:0003378	Axonal degeneration/regeneration
HP:0003383	Onion bulb formation
HP:0003393	Thenar muscle atrophy
HP:0003394	Muscle spasm
HP:0003445	EMG: neuropathic changes
HP:0003481	Segmental peripheral demyelination/remyelination
HP:0003596	Middle age onset
HP:0003693	Distal amyotrophy
HP:0007107	Segmental peripheral demyelination
HP:0009027	Foot dorsiflexor weakness
HP:0011462	Young adult onset
HP:0011463	Childhood onset

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002500_66	QT interval	3.000000e-08
GCST005235_18	Hand grip strength	1.000000e-09
GCST005316_346	Intelligence (MTAG)	4.000000e-09
GCST005316_352	Intelligence (MTAG)	9.000000e-10
GCST005316_74	Intelligence (MTAG)	2.000000e-13
GCST005956_50	Waist-to-hip ratio adjusted for BMI	8.000000e-06
GCST005958_15	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-06
GCST005962_36	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST006269_323	General cognitive ability	2.000000e-11
GCST008810_89	Smoking initiation (ever regular vs never regular)	2.000000e-08
GCST009325_2	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-09
GCST009524_145	Household income (MTAG)	1.000000e-12
GCST009524_82	Household income (MTAG)	2.000000e-08
GCST010002_298	Refractive error	3.000000e-22
GCST010173_177	Triglyceride levels	1.000000e-08
GCST010988_449	Adult body size	4.000000e-10
GCST90002388_574	Lymphocyte count	9.000000e-10
GCST90002389_454	Lymphocyte percentage of white cells	2.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0006941	grip strength measurement
EFO:0004337	intelligence
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0005670	smoking initiation
EFO:0009695	household income
EFO:0004530	triglyceride measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535344	Cataract, posterior polar, 4 (supp.)
C564702	Charcot-Marie-Tooth Disease, Dominant Intermediate A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Quercetin	increases expression, increases phosphorylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
coumarin	affects phosphorylation	1
cupric oxide	increases phosphorylation	1
ICG 001	decreases expression	1
abrine	increases expression	1
pentabrominated diphenyl ether 100	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
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Ivermectin	decreases expression	1
Dronabinol	increases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01847937	Not specified	COMPLETED	Magnetic Resonance Diagnostics of Diabetic Peripheral Neuropathy
NCT05641103	Not specified	COMPLETED	PREDIGA 2: Spanish Acronym of Educational and Diagnostic Project for Gaucher and ASMD