MON1A

Summary

MON1A (MON1 vesicular trafficking associated A, HGNC:28207) is a protein-coding gene on chromosome 3p21.31, encoding Vacuolar fusion protein MON1 homolog A (Q86VX9). Plays an important role in membrane trafficking through the secretory apparatus.

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in protein secretion. Predicted to act upstream of or within establishment of localization in cell; intracellular iron ion homeostasis; and protein transport. Part of Mon1-Ccz1 complex.

Source: NCBI Gene 84315 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 87 total — 1 likely-pathogenic
• MANE Select transcript: NM_032355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28207
Approved symbol	MON1A
Name	MON1 vesicular trafficking associated A
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC13272, SAND1
Ensembl gene	ENSG00000164077
Ensembl biotype	protein_coding
OMIM	611464
Entrez	84315

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000296473, ENST00000417270, ENST00000455683, ENST00000473451, ENST00000483022, ENST00000486107, ENST00000493206, ENST00000642691, ENST00000645862, ENST00000864154, ENST00000864155, ENST00000864156, ENST00000864157, ENST00000864158, ENST00000864159, ENST00000948760, ENST00000948761, ENST00000948762, ENST00000948763, ENST00000948764, ENST00000948765, ENST00000948766

RefSeq mRNA: 2 — MANE Select: NM_032355 NM_001142501, NM_032355

CCDS: CCDS2808, CCDS46830

Canonical transcript exons

ENST00000296473 — 6 exons

Exon	Start	End
ENSE00001081170	49911526	49912011
ENSE00001350848	49909253	49909400
ENSE00001376118	49910119	49910884
ENSE00001627622	49908873	49909154
ENSE00003603702	49929609	49929811
ENSE00003823082	49913220	49913359

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 87.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.1930 / max 44.0516, expressed in 1683 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42287	4.3425	1645
42288	0.8505	536

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	87.81	gold quality
kidney epithelium	UBERON:0004819	86.70	gold quality
prefrontal cortex	UBERON:0000451	86.26	gold quality
cortical plate	UBERON:0005343	85.77	gold quality
right frontal lobe	UBERON:0002810	85.11	gold quality
anterior cingulate cortex	UBERON:0009835	84.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.38	gold quality
frontal cortex	UBERON:0001870	83.76	gold quality
gastrocnemius	UBERON:0001388	83.67	gold quality
neocortex	UBERON:0001950	83.65	gold quality
duodenum	UBERON:0002114	83.35	gold quality
muscle of leg	UBERON:0001383	82.87	gold quality
amygdala	UBERON:0001876	82.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.84	gold quality
epithelial cell of pancreas	CL:0000083	82.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.78	gold quality
apex of heart	UBERON:0002098	82.72	gold quality
mucosa of transverse colon	UBERON:0004991	82.55	gold quality
hypothalamus	UBERON:0001898	82.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.35	gold quality
putamen	UBERON:0001874	82.32	gold quality
nucleus accumbens	UBERON:0001882	82.14	gold quality
spinal cord	UBERON:0002240	82.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.00	gold quality
cerebral cortex	UBERON:0000956	81.98	gold quality
caudate nucleus	UBERON:0001873	81.83	gold quality
jejunal mucosa	UBERON:0000399	81.80	gold quality
substantia nigra	UBERON:0002038	81.45	gold quality
forebrain	UBERON:0001890	81.38	gold quality
granulocyte	CL:0000094	81.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting MON1A, 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-6752-3P	99.72	66.71	1587
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628

Literature-anchored findings (GeneRIF, showing 1)

• a role for Mon1a in anterograde trafficking through the secretory apparatus. (PMID:22665492)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mon1a	ENSDARG00000078585
mus_musculus	Mon1a	ENSMUSG00000032583
rattus_norvegicus	Mon1a	ENSRNOG00000018502
drosophila_melanogaster	Mon1	FBGN0031640
caenorhabditis_elegans		WBGENE00018321

Paralogs (1): MON1B (ENSG00000103111)

Protein

Protein identifiers

Vacuolar fusion protein MON1 homolog A — Q86VX9 (reviewed: Q86VX9)

All UniProt accessions (2): A0A0A0MSQ9, Q86VX9

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in membrane trafficking through the secretory apparatus. Not involved in endocytic trafficking to lysosomes. Acts in concert with CCZ1, as a guanine exchange factor (GEF) for RAB7, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form.

Subunit / interactions. Interacts with CCZ1. Found in a complex with RMC1, CCZ1, MON1A and MON1B. The MON1A-CCZ1B complex interacts with RIMOC1. The MON1A-CCZ1B complex interacts with RAB7A and this interaction is enhanced in the presence of RIMOC1.

Similarity. Belongs to the MON1/SAND family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q86VX9-1	1	yes
Q86VX9-2	2
Q86VX9-3	3
Q86VX9-4	4
Q86VX9-5	5

RefSeq proteins (2): NP_001135973, NP_115731* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004353	Mon1	Family
IPR043970	FUZ/MON1/HPS1_longin_3	Domain
IPR043971	FUZ/MON1/HPS1_longin_2	Domain
IPR043972	FUZ/MON1/HPS1_longin_1	Domain

Pfam: PF19036, PF19037, PF19038

UniProt features (13 total): splice variant 4, modified residue 4, region of interest 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9LOL	ELECTRON MICROSCOPY	2.85
9L0D	ELECTRON MICROSCOPY	3.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VX9-F1	73.30	0.55

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 (4): 128, 153, 158, 188

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 97 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, AAGCCAT_MIR135A_MIR135B, GOBP_PROTEIN_TARGETING, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GGAMTNNNNNTCCY_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, MYCMAX_01, USF_01, GOBP_SECRETION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_VACUOLE, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, P53_DECAMER_Q2

GO Biological Process (3): protein targeting to vacuole (GO:0006623), protein secretion (GO:0009306), vesicle-mediated transport (GO:0016192)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), Mon1-Ccz1 complex (GO:0035658)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein targeting	1
intracellular protein transport	1
vacuolar transport	1
protein localization to vacuole	1
establishment of protein localization to vacuole	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
transport	1
cellular process	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1
late endosome	1
guanyl-nucleotide exchange factor complex	1

Protein interactions and networks

STRING

1088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MON1A	CCZ1B	P86790	999
MON1A	RAB5A	P20339	967
MON1A	RABGEF1	Q9UJ41	841
MON1A	WDHD1	O75717	717
MON1A	GAPVD1	Q14C86	715
MON1A	RABEP1	Q15276	714
MON1A	EEA1	Q15075	695
MON1A	RABIF	P47224	675
MON1A	VPS39	Q96JC1	669
MON1A	APPL1	Q9UKG1	609
MON1A	VPS11	Q9H270	588
MON1A	VPS18	Q9P253	586
MON1A	VPS8	Q8N3P4	584
MON1A	SLC40A1	Q9NP59	575
MON1A	VPS16	Q9H269	575

IntAct

18 interactions, top by confidence:

A	B	Type	Score
MON1A	CCZ1	psi-mi:“MI:0915”(physical association)	0.590
MON1A	CCZ1	psi-mi:“MI:0914”(association)	0.590
CCZ1	RAB7A	psi-mi:“MI:2252”(guanine nucleotide exchange factor reaction)	0.590
SP6	CCZ1B	psi-mi:“MI:0914”(association)	0.530
rabx-5	MON1A	psi-mi:“MI:0915”(physical association)	0.460
VPS33A	MON1A	psi-mi:“MI:0915”(physical association)	0.400
TAB1	MON1A	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	MON1A	psi-mi:“MI:0915”(physical association)	0.370
MON1A	RGS2	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
SP6	GNB2	psi-mi:“MI:0914”(association)	0.350
RMC1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
RMC1	ARID1A	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
SP6	GPX1	psi-mi:“MI:0914”(association)	0.350
MON1A	MON1B	psi-mi:“MI:0403”(colocalization)	0.270
GFI1B	MON1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): MON1A (Affinity Capture-MS), MON1A (Co-fractionation), MON1A (Affinity Capture-MS), MON1A (Affinity Capture-MS), RAB7A (Co-localization), MON1A (Affinity Capture-MS), MON1A (Affinity Capture-MS), MON1A (Affinity Capture-MS), MON1A (Affinity Capture-MS), MON1A (Affinity Capture-Western), MON1A (Affinity Capture-Western), MON1A (Affinity Capture-MS), MON1A (Two-hybrid), MON1A (Two-hybrid), MON1A (Two-hybrid)

ESM2 similar proteins: A3R064, D3ZBP4, F1MH07, G3V8H4, O15211, O70248, O88888, O95382, O96018, P22455, P70218, Q0QWG9, Q12851, Q13470, Q14B98, Q2TBQ9, Q3MIN7, Q3UYI5, Q3V3V9, Q61085, Q61161, Q61193, Q6F5E8, Q6P597, Q6P5Z2, Q6P9Q4, Q80XL1, Q86UT5, Q86VX9, Q8BWA8, Q8IW93, Q8K031, Q8K045, Q8R5F8, Q8TDZ2, Q8TE68, Q8VDP3, Q92502, Q92918, Q969H4

Diamond homologs: A1CEH4, P0CO82, P0CO83, P53129, Q0CJY1, Q0U822, Q10150, Q17QV2, Q1E8Q5, Q2HFQ4, Q2ULR1, Q4I6S5, Q4R4E4, Q4WHL1, Q5BBI7, Q5ZIH2, Q6CCU8, Q6FU19, Q6PDG8, Q75EA2, Q7L1V2, Q86VX9, Q870Q4, Q8BMQ8, Q95KG9, Q9VR38, Q9YGN1, Q4PA36, Q5JL08, Q9SKN1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MON1A	“form complex”	“MON1-CCZ1 guanyl-nucleotide exchange factor complex, MON1A variant”	binding
MON1A	“form complex”	“MON1-CCZ1B guanyl-nucleotide exchange factor complex, MON1A variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	80
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3252073	NM_032355.4(MON1A):c.454C>T (p.Arg152Cys)	Likely pathogenic

SpliceAI

890 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49909152:CAC:C	acceptor_gain	1.0000
3:49909247:CCTTA:C	donor_loss	1.0000
3:49909248:CTTA:C	donor_loss	1.0000
3:49909249:TTA:T	donor_loss	1.0000
3:49909250:TACCC:T	donor_loss	1.0000
3:49909251:A:AC	donor_gain	1.0000
3:49909251:A:T	donor_loss	1.0000
3:49909251:AC:A	donor_gain	1.0000
3:49909251:ACC:A	donor_gain	1.0000
3:49909252:C:CA	donor_loss	1.0000
3:49909252:C:CC	donor_gain	1.0000
3:49909252:CC:C	donor_gain	1.0000
3:49909252:CCC:C	donor_gain	1.0000
3:49909252:CCCAG:C	donor_gain	1.0000
3:49909396:CAGGG:C	acceptor_gain	1.0000
3:49909398:GGG:G	acceptor_gain	1.0000
3:49909399:GGC:G	acceptor_loss	1.0000
3:49909400:GCTG:G	acceptor_loss	1.0000
3:49909401:C:CC	acceptor_gain	1.0000
3:49909401:C:CG	acceptor_loss	1.0000
3:49910113:CCTCA:C	donor_loss	1.0000
3:49910114:CTCAC:C	donor_loss	1.0000
3:49910115:TCACC:T	donor_loss	1.0000
3:49910116:CA:C	donor_loss	1.0000
3:49910117:ACCTG:A	donor_loss	1.0000
3:49910118:C:CA	donor_loss	1.0000
3:49910881:CCAT:C	acceptor_gain	1.0000
3:49910882:CAT:C	acceptor_gain	1.0000
3:49910882:CATC:C	acceptor_gain	1.0000
3:49910885:C:CC	acceptor_gain	1.0000

AlphaMissense

4208 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49910367:G:C	F474L	1.000
3:49910367:G:T	F474L	1.000
3:49910369:A:G	F474L	1.000
3:49910408:A:G	W461R	1.000
3:49910408:A:T	W461R	1.000
3:49909075:A:G	L633P	0.999
3:49909135:A:G	L613P	0.999
3:49909140:A:C	F611L	0.999
3:49909140:A:T	F611L	0.999
3:49909142:A:G	F611L	0.999
3:49910150:A:C	Y547D	0.999
3:49910154:G:C	F545L	0.999
3:49910154:G:T	F545L	0.999
3:49910155:A:G	F545S	0.999
3:49910156:A:G	F545L	0.999
3:49910289:G:C	F500L	0.999
3:49910289:G:T	F500L	0.999
3:49910291:A:G	F500L	0.999
3:49910406:C:A	W461C	0.999
3:49910406:C:G	W461C	0.999
3:49910446:A:G	L448P	0.999
3:49910458:A:G	L444P	0.999
3:49910665:A:G	L375P	0.999
3:49910710:T:C	D360G	0.999
3:49910763:G:C	S342R	0.999
3:49910763:G:T	S342R	0.999
3:49910765:T:G	S342R	0.999
3:49910865:G:C	F308L	0.999
3:49910865:G:T	F308L	0.999
3:49910867:A:G	F308L	0.999

dbSNP variants (sampled 300 via entrez): RS1000097935 (3:49927176 G>A), RS1000760908 (3:49917256 G>A), RS1000854662 (3:49917433 C>T), RS1001200570 (3:49926536 A>G), RS1001367721 (3:49911474 G>A), RS1001669166 (3:49918104 A>G), RS1002050256 (3:49914611 G>A,C), RS1002187020 (3:49928371 A>T), RS1002196423 (3:49924199 C>A), RS1002262318 (3:49916855 T>A,C), RS1002396839 (3:49919770 A>T), RS1002398868 (3:49931703 C>A), RS1002449227 (3:49920147 C>T), RS1002708108 (3:49928129 C>A), RS1002759260 (3:49909701 G>A)

Disease associations

OMIM: gene MIM:611464 | disease phenotypes: MIM:214700

GenCC curated gene-disease

Mondo (1): congenital diarrhea (MONDO:0000824)

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST002783_172	Body mass index	7.000000e-07
GCST002783_226	Body mass index	5.000000e-07
GCST002783_571	Body mass index	1.000000e-06
GCST003795_3	Age at first birth	5.000000e-15
GCST004904_256	Body mass index	4.000000e-09
GCST005316_122	Intelligence (MTAG)	3.000000e-08
GCST006044_2	Age at first birth	2.000000e-06
GCST006045_5	Age at first birth	6.000000e-10
GCST006920_7	Regular attendance at a gym or sports club	6.000000e-10
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST008129_41	Body mass index	9.000000e-26
GCST008832_17	Gastroesophageal reflux disease	3.000000e-08
GCST009524_76	Household income (MTAG)	2.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST90002397_653	Mean spheric corpuscular volume	5.000000e-13
GCST90020029_1181	Waist circumference adjusted for body mass index	3.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009101	age at first birth measurement
EFO:0004337	intelligence
EFO:0009592	social interaction measurement
EFO:0009695	household income
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
jinfukang	increases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Oxygen	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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