MON2

Summary

MON2 (MON2 regulator of endosome-to-Golgi trafficking, HGNC:29177) is a protein-coding gene on chromosome 12q14.1, encoding Protein MON2 homolog (Q7Z3U7). Plays a role in regulating membrane trafficking of cargo proteins. It is a selective cancer dependency (DepMap: 11.8% of cell lines).

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in Golgi to endosome transport; protein targeting to vacuole; and retrograde transport, endosome to Golgi. Located in Golgi apparatus and early endosome membrane.

Source: NCBI Gene 23041 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 197 total
• GTEx eGene: eQTL in 5 tissues, sQTL in 10 (q < 0.05)
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.43 (moderately constrained)
• MANE Select transcript: NM_015026
• Notable: 197 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29177
Approved symbol	MON2
Name	MON2 regulator of endosome-to-Golgi trafficking
Location	12q14.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1040
Ensembl gene	ENSG00000061987
Ensembl biotype	protein_coding
OMIM	616822
Entrez	23041

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 17 protein_coding, 7 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000393630

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 6, TSL 2: 3, TSL 3: 2, TSL 5: 2

ENST00000393630, ENST00000393629, ENST00000546600, ENST00000546751, ENST00000547095, ENST00000547287, ENST00000549286, ENST00000549378, ENST00000549539, ENST00000551307, ENST00000551397, ENST00000552115, ENST00000552738, ENST00000641654, ENST00000854041, ENST00000854042, ENST00000854043, ENST00000914365, ENST00000953601, ENST00000953602, ENST00000953603, ENST00001042052, ENST00001042053, ENST00001042054, ENST00001042055, ENST00001095384, ENST00001111714, ENST00001116728, ENST00001116729, ENST00001139050

RefSeq mRNA: 5 — MANE Select: NM_015026 NM_001278469, NM_001278470, NM_001278471, NM_001278472, NM_015026

CCDS: CCDS31849, CCDS61175, CCDS61177, CCDS61178

Canonical transcript exons

ENST00000393630 — 35 exons

Exon	Start	End
ENSE00003459455	62532438	62532670
ENSE00003464043	62508286	62508480
ENSE00003468543	62580297	62580420
ENSE00003470669	62535525	62535709
ENSE00003472122	62566014	62566031
ENSE00003486231	62588074	62588156
ENSE00003490119	62538096	62538176
ENSE00003497690	62493915	62494042
ENSE00003501225	62565237	62565380
ENSE00003507393	62560491	62561113
ENSE00003514713	62537151	62537263
ENSE00003515746	62585294	62585501
ENSE00003516432	62555994	62556192
ENSE00003525510	62544898	62545008
ENSE00003547960	62571392	62571582
ENSE00003552003	62534845	62534926
ENSE00003559463	62525949	62526102
ENSE00003566789	62538415	62538505
ENSE00003576516	62552881	62553174
ENSE00003578128	62546897	62547072
ENSE00003578227	62578445	62578505
ENSE00003578575	62501573	62501698
ENSE00003578903	62537602	62537706
ENSE00003579576	62484170	62484233
ENSE00003583757	62543097	62543198
ENSE00003584395	62524515	62524639
ENSE00003606969	62498919	62499048
ENSE00003637152	62495016	62495147
ENSE00003639645	62538252	62538325
ENSE00003647058	62566322	62566450
ENSE00003656431	62525084	62525220
ENSE00003670276	62500783	62500880
ENSE00003690110	62549668	62549830
ENSE00003841246	62466826	62467318
ENSE00004794080	62592586	62600476

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 95.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6418 / max 342.1206, expressed in 1815 samples.

Highest expression (Bgee): body of pancreas, tibia, calcaneal tendon, mucosa of paranasal sinus, tibial nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MON2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	1.8e-09	-0.41	12:62586800:T:A
Lung	sqtl	2.1e-08	-0.27	12:62581527:C:T
Artery Aorta	eqtl	2.2e-07	+0.24	12:62273946:T:C
Skin Sun Exposed Lower leg	sqtl	2.6e-07	-0.32	12:62570772:T:C
Nerve Tibial	sqtl	2.6e-06	-0.38	12:62605374:C:G
Artery Tibial	sqtl	2.7e-05	-0.33	12:62567100:A:G
Adipose Visceral Omentum	sqtl	5.0e-05	-0.33	12:62592091:C:A
Adipose Subcutaneous	sqtl	6.4e-05	-0.30	12:62581527:C:T
Pituitary	sqtl	9.2e-03	-0.42	12:62592840:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-02	-0.10	12:62453005:T:C
Artery Aorta	sqtl	1.2e-02	-0.32	12:62586800:T:A
Breast Mammary Tissue	sqtl	1.4e-02	-0.33	12:62551465:G:A
Thyroid	eqtl	1.5e-02	+0.13	12:62600162:G:A
Lung	eqtl	2.3e-02	+0.41	12:62811827:C:A
Esophagus Muscularis	eqtl	3.6e-02	+0.13	12:63148572:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
126396	32.6418	1815

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	95.98	gold quality
tibia	UBERON:0000979	95.44	gold quality
calcaneal tendon	UBERON:0003701	94.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.71	gold quality
tibial nerve	UBERON:0001323	94.61	gold quality
adrenal tissue	UBERON:0018303	94.54	gold quality
corpus callosum	UBERON:0002336	94.38	gold quality
right uterine tube	UBERON:0001302	94.20	gold quality
skin of leg	UBERON:0001511	93.51	gold quality
left ovary	UBERON:0002119	93.45	gold quality
skin of abdomen	UBERON:0001416	93.34	gold quality
minor salivary gland	UBERON:0001830	93.33	gold quality
pylorus	UBERON:0001166	93.24	gold quality
mucosa of stomach	UBERON:0001199	93.22	gold quality
left lobe of thyroid gland	UBERON:0001120	93.07	gold quality
adenohypophysis	UBERON:0002196	92.98	gold quality
right lobe of liver	UBERON:0001114	92.97	gold quality
endocervix	UBERON:0000458	92.96	gold quality
descending thoracic aorta	UBERON:0002345	92.93	gold quality
right ovary	UBERON:0002118	92.90	gold quality
superficial temporal artery	UBERON:0001614	92.89	gold quality
thyroid gland	UBERON:0002046	92.89	gold quality
right lobe of thyroid gland	UBERON:0001119	92.75	gold quality
superior surface of tongue	UBERON:0007371	92.72	gold quality
saliva-secreting gland	UBERON:0001044	92.70	gold quality
zone of skin	UBERON:0000014	92.61	gold quality
pituitary gland	UBERON:0000007	92.60	gold quality
popliteal artery	UBERON:0002250	92.59	gold quality
tibial artery	UBERON:0007610	92.59	gold quality
aorta	UBERON:0000947	92.49	gold quality
ascending aorta	UBERON:0001496	92.46	gold quality
metanephros cortex	UBERON:0010533	92.42	gold quality
ectocervix	UBERON:0012249	92.41	gold quality
thoracic aorta	UBERON:0001515	92.40	gold quality
body of uterus	UBERON:0009853	92.35	gold quality
cardia of stomach	UBERON:0001162	92.29	gold quality
left coronary artery	UBERON:0001626	92.20	gold quality
mouth mucosa	UBERON:0003729	92.17	gold quality
right coronary artery	UBERON:0001625	92.16	gold quality
right lung	UBERON:0002167	92.11	gold quality
coronary artery	UBERON:0001621	92.05	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.76	gold quality
tongue squamous epithelium	UBERON:0006919	91.76	silver quality
pancreas	UBERON:0001264	91.75	gold quality
peritoneum	UBERON:0002358	91.74	gold quality
omental fat pad	UBERON:0010414	91.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.66	gold quality
rectum	UBERON:0001052	91.62	gold quality
fundus of stomach	UBERON:0001160	91.61	gold quality
epithelium of nasopharynx	UBERON:0001951	91.50	gold quality
adipose tissue	UBERON:0001013	91.44	gold quality
vagina	UBERON:0000996	91.42	gold quality
bronchial epithelial cell	CL:0002328	91.41	gold quality
uterine cervix	UBERON:0000002	91.38	gold quality
jejunal mucosa	UBERON:0000399	91.31	gold quality
connective tissue	UBERON:0002384	91.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.26	gold quality
inferior vagus X ganglion	UBERON:0005363	91.18	gold quality
spleen	UBERON:0002106	91.14	gold quality
cervix squamous epithelium	UBERON:0006922	91.14	silver quality
stomach	UBERON:0000945	91.13	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.09	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.08	gold quality
tonsil	UBERON:0002372	91.07	gold quality
body of stomach	UBERON:0001161	90.94	gold quality
hair follicle	UBERON:0002073	90.90	gold quality
transverse colon	UBERON:0001157	90.84	gold quality
upper leg skin	UBERON:0004262	90.83	gold quality
upper lobe of left lung	UBERON:0008952	90.80	gold quality
endometrium	UBERON:0001295	90.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.78	gold quality
substantia nigra pars compacta	UBERON:0001965	90.76	gold quality
sural nerve	UBERON:0015488	90.75	gold quality
liver	UBERON:0002107	90.72	gold quality
subthalamic nucleus	UBERON:0001906	90.70	gold quality
sigmoid colon	UBERON:0001159	90.68	gold quality
bone marrow cell	CL:0002092	90.62	gold quality
upper lobe of lung	UBERON:0008948	90.58	gold quality
esophagus mucosa	UBERON:0002469	90.57	gold quality
lateral globus pallidus	UBERON:0002476	90.56	gold quality
secondary oocyte	CL:0000655	90.54	gold quality
buccal mucosa cell	CL:0002336	90.54	gold quality
uterus	UBERON:0000995	90.54	gold quality
lower esophagus	UBERON:0013473	90.54	gold quality
ovary	UBERON:0000992	90.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.53	gold quality
esophagus	UBERON:0001043	90.52	gold quality
intestine	UBERON:0000160	90.48	gold quality
colon	UBERON:0001155	90.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.47	gold quality
saphenous vein	UBERON:0007318	90.46	gold quality
right adrenal gland cortex	UBERON:0035827	90.43	gold quality
tendon	UBERON:0000043	90.42	gold quality
mucosa of urinary bladder	UBERON:0001259	90.42	silver quality
large intestine	UBERON:0000059	90.41	gold quality
small intestine	UBERON:0002108	90.29	gold quality
duodenum	UBERON:0002114	90.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.25	gold quality
lower esophagus mucosa	UBERON:0035834	90.23	gold quality
oral cavity	UBERON:0000167	90.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.09

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	40.9
Corpus callosum	tissue	39.0
Cerebellum	tissue	35.4
Midbrain	tissue	32.5
Nucleus accumbens	tissue	31.0
Spinal cord	tissue	30.8
Medulla oblongata	tissue	30.5
Thalamus	tissue	29.9
Superior colliculi	tissue	29.5
Cerebral cortex	tissue	29.0
Somatosensory cortex	tissue	29.0
Substantia nigra	tissue	28.8
Pons	tissue	28.2
Hypothalamus	tissue	28.2
Putamen	tissue	28.0
Hippocampus	tissue	28.0
Motor cortex	tissue	27.8
Occipital cortex	tissue	27.6
Retrosplenial and cingulate cortex	tissue	27.4
Periaqueductal gray	tissue	27.4
Hippocampal formation	tissue	27.3
Olfactory bulb	tissue	27.3
Retrosplenial cortex	tissue	27.2
Ventral forebrain	tissue	26.9
Postcentral gyrus	tissue	26.8
Septum	tissue	26.8
Entorhinal cortex	tissue	26.6
Prefrontal cortex	tissue	26.5
Locus coeruleus	tissue	26.3
Temporal cortex	tissue	25.9
Insular cortex	tissue	25.0
Amygdala	tissue	24.7
Basal ganglia	tissue	22.6
Retina	tissue	16.1
Caudate putamen	tissue	15.6
Parathyroid gland	tissue	14.5
Frontal cortex	tissue	13.9
Liver	tissue	13.3
Pancreas	tissue	13.0
Thyroid gland	tissue	12.2
Thymus	tissue	11.8
Salivary gland	tissue	11.7
Cervix	tissue	11.0
Stomach 1	tissue	10.1
Endometrium 1	tissue	10.0
Rectum	tissue	9.8
Placenta	tissue	9.7
Kidney	tissue	9.6
Prostate	tissue	9.3
Ovary	tissue	9.2
Adipose tissue	tissue	9.2
Tonsil	tissue	9.2
Breast	tissue	8.9
Spleen	tissue	8.9
Lymph node	tissue	8.8
Skin 1	tissue	8.6
Smooth muscle	tissue	8.6
Bone marrow	tissue	8.6
Appendix	tissue	8.6
Esophagus	tissue	8.5

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (60.3), Corpus callosum, genu (white matter) (56.5), Corpus callosum, splenium (white matter) (54.7), Temporal white matter (49.8), Cerebellar white matter (49.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MON2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 227 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.426, missense Z 3.76 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000393630 — one region, missense o/e 0.80. DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): M040416 (-1.358), EJM (-1.14), MDA-MB-157 (-1.086), UACC-3199 (-1.064), UM-UC-10 (-1.016), NCI-H211 (-1.008), DAN-G (-0.979), NGP (-0.947), DK-MG (-0.917), NCI-H1693 (-0.898), MOLM-13 (-0.889), HuH-6 (-0.878), ABC-1 (-0.877), MDA-MB-415 (-0.874), SCS-214 (-0.856).

Literature-anchored findings (GeneRIF, showing 5)

• Ysl2p represents an essential, evolutionarily conserved member of a network controlling direct binding and membrane docking of Ggas. (PMID:18418388)
• Depletion of hVps18 or hMon2 reduced the efficient production of infectious HIV-1 virions in human cells. (PMID:21450827)
• Mon2 is involved in endosome-to-Golgi trafficking as its depletion accelerated the delivery of furin and CI-M6PR to Golgi after endocytosis. (PMID:24285343)
• an evolutionary conserved MON2:DOPEY2:ATP9A complex is required for SNX3 retromer mediation of Wntless sorting and Wnt secretion (PMID:30213940)
• MicroRNA-133a-5p inhibiting metastatic capacity of renal clear cell carcinoma through regulating MON2. (PMID:32572912)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mon2	ENSDARG00000099798
mus_musculus	Mon2	ENSMUSG00000034602
rattus_norvegicus	Mon2	ENSRNOG00000004185
drosophila_melanogaster	mon2	FBGN0031985
caenorhabditis_elegans		WBGENE00008685

Paralogs (15): CYTH3 (ENSG00000008256), PSD (ENSG00000059915), ARFGEF1 (ENSG00000066777), CYTH4 (ENSG00000100055), CYTH2 (ENSG00000105443), GBF1 (ENSG00000107862), CYTH1 (ENSG00000108669), IQSEC3 (ENSG00000120645), ARFGEF2 (ENSG00000124198), IQSEC2 (ENSG00000124313), PSD4 (ENSG00000125637), IQSEC1 (ENSG00000144711), PSD2 (ENSG00000146005), PSD3 (ENSG00000156011), FBXO8 (ENSG00000164117)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914324) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vocalization	1
abnormal coat/hair pigmentation	1
increased heart weight	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila pseudoobscura pseudoobscura	Q29L43	93.7%	Diamond
Caenorhabditis briggsae	Q61SD1	92.5%	Diamond
Xenopus laevis	Q6GP04	87.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MON2-AS1	ncRNA	128385372
TAFA2	protein-coding	338811
USP15	protein-coding	9958
MIR6125	ncRNA	102465133
MIRLET7IHG	ncRNA	120766144
LINC01465	ncRNA	283416
MIRLET7I	ncRNA	406891
PPM1H	protein-coding	57460

Protein

Protein identifiers

Protein MON2 homolog — Q7Z3U7 (reviewed: Q7Z3U7)

Alternative names: Protein SF21

All UniProt accessions (5): Q7Z3U7, A0A286YFF8, F8VQS2, F8VZV1, F8VZV6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in regulating membrane trafficking of cargo proteins. Together with ATP9A and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS away from lysosomal degradation.

Subunit / interactions. Homooligomer. Heterotrimer with ATP9A and DOP1B; this interaction is retromer-independent. Interacts with SNX3.

Subcellular location. Early endosome membrane.

Similarity. Belongs to the MON2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q7Z3U7-1	1	yes
Q7Z3U7-2	2
Q7Z3U7-3	3
Q7Z3U7-5	5
Q7Z3U7-6	6

RefSeq proteins (5): NP_001265398, NP_001265399, NP_001265400, NP_001265401, NP_055841* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015403	Mon2/Sec7/BIG1-like_HDS	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR032629	DCB_dom	Domain
IPR032691	Mon2/Sec7/BIG1-like_HUS	Domain
IPR032817	Mon2_C	Domain

Pfam: PF09324, PF12783, PF16206, PF16213

UniProt features (22 total): sequence conflict 8, splice variant 6, modified residue 3, initiator methionine 1, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3U7-F1	78.50	0.30

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli fibrillar center; nucleoplasm

Antibody reliability (HPA): IH uncertain · IF approved

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 (3)

Type	Positions
N-acetylserine	2
Phosphoserine	205, 537

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 207 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, MORF_FLT1, YAGI_AML_WITH_INV_16_TRANSLOCATION, MORF_MSH3, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PROTEIN_TARGETING, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MORF_RAD51L3, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, ACATTCC_MIR1_MIR206

GO Biological Process (5): protein targeting to vacuole (GO:0006623), Golgi to endosome transport (GO:0006895), retrograde transport, endosome to Golgi (GO:0042147), regulation of retrograde transport, endosome to Golgi (GO:1905279), protein transport (GO:0015031)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), early endosome membrane (GO:0031901), endolysosome (GO:0036019), extracellular exosome (GO:0070062)

GO top-level categories

28 GO namespaces:

Category	Terms
cytoplasm	3
cytosolic transport	2
endomembrane system	2
intracellular membrane-bounded organelle	2
protein targeting	1
intracellular protein transport	1
vacuolar transport	1
protein localization to vacuole	1
establishment of protein localization to vacuole	1
post-Golgi vesicle-mediated transport	1
endosomal transport	1
regulation of intracellular transport	1
retrograde transport, endosome to Golgi	1
regulation of vesicle-mediated transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
protein binding	1
cellular anatomical structure	1
early endosome	1
endosome membrane	1
lysosome	1
endosome	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi apparatus	CC	direct assay
early endosome membrane	CC	direct assay
extracellular exosome	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,104 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MON2	NEO1	Q92859	799
MON2	CYTH1	Q15438	722
MON2	DOP1A	Q5JWR5	693
MON2	SNX3	O60493	551
MON2	DOP1B	Q9Y3R5	548
MON2	PAK1IP1	Q9NWT1	525
MON2	HTATSF1	O43719	498
MON2	SMIM8	Q96KF7	491
MON2	ATP9A	O75110	487
MON2	CDC40	O60508	479
MON2	ZFP91	Q96JP5	478
MON2	FBXO38	Q6PIJ6	474
MON2	TBC1D22A	Q8WUA7	461
MON2	ARFRP1	Q13795	456
MON2	ATP9B	O43861	452

IntAct

Human interaction partners of MON2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
DOP1A	physical association	0.680	9
GGA1	physical association	0.520	2
GGA2	physical association	0.400	1
GGA3	physical association	0.400	1
HMGN2	physical association	0.400	1
SPTAN1	physical association	0.400	1
ECE1	physical association	0.370	1
TNFRSF1A	physical association	0.000	2
MTNR1B	physical association	0.000	1
STOM	physical association	0.000	1
TNFRSF1B	physical association	0.000	1

BioGRID (197 interactions; top human partners by supporting records): TNFSF13B (Affinity Capture-MS; 3 records), CA14 (Affinity Capture-MS; 2 records), EGFR (Affinity Capture-MS; 2 records), FGFR1 (Affinity Capture-MS; 2 records), MFSD4 (Affinity Capture-MS; 2 records), NTRK1 (Affinity Capture-MS; 2 records), OPRM1 (Affinity Capture-MS; 2 records), SIGLECL1 (Affinity Capture-MS; 2 records), VASN (Affinity Capture-MS; 2 records), ABHD12 (Affinity Capture-MS), ACPP (Affinity Capture-MS), AGO2 (Affinity Capture-RNA), ANKFY1 (Co-fractionation), AQP3 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
MON2	“form complex”	“ATP9A-DOP1B-MON2, golgi transporter complex”	binding
MON2	“form complex”	“DOP1A-MON2, golgi-endosome traffic complex”	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
ATP9A-DOP1B-MON2 complex	3	ATP9A, DOP1B, MON2

Disease & clinical

Genetic variants

Variant evidence for MON2: 197 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	154
Likely benign	5
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 3,405):

Position(s)	Effect	Δscore	Sites
12:62467319–62467320	donor_loss	1.0000	4
12:62487080	acceptor_gain	1.0000
12:62493899	acceptor_gain	1.0000
12:62493908–62493910	acceptor_gain	1.0000	2
12:62498917–62498918	acceptor_loss	1.0000	6
12:62499049–62499050	donor_loss	1.0000	2
12:62508281	acceptor_gain	1.0000
12:62524546	acceptor_gain	1.0000
12:62524640–62524641	donor_loss	1.0000	5
12:62532436–62532437	acceptor_loss	1.0000	5

AlphaMissense

5,579 missense substitutions predicted likely pathogenic (of 11,193 scored), across 1,263 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M241	9	0.995	1.000
M115	9	0.955	0.997
M238	9	0.899	0.998
M470	9	0.835	0.977
D222	8	0.999	1.000
D977	8	0.999	1.000
H1101	8	0.999	1.000
H1102	8	0.999	1.000
D377	8	0.998	0.999
F245	8	0.997	1.000
F283	8	0.997	1.000
F335	8	0.997	1.000
F151	8	0.996	0.999
N963	8	0.996	1.000
F793	8	0.995	1.000
D215	8	0.994	0.999
F261	8	0.994	0.999
F754	8	0.994	0.999
D935	8	0.992	0.998
H1055	8	0.991	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000123

Disease associations

OMIM: gene MIM:616822 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST010244_423	Triglyceride levels	7e-11
GCST90020025_1343	Waist-to-hip ratio adjusted for BMI	6e-9
GCST90020027_287	Waist-hip index	1e-8
GCST002379_4	Pyoderma gangrenosum in inflammatory bowel disease	5e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0006835	pyoderma gangrenosum
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105804 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.42	Kd	3.821	nM	CHEMBL3752910
8.42	ED50	3.821	nM	CHEMBL3752910
6.72	Kd	191.3	nM	CHEMBL5653589
6.72	ED50	191.3	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148763: Binding affinity to human MON2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0038	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148763: Binding affinity to human MON2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1913	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Endosulfan	decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Nickel	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
titanium dioxide	decreases methylation, increases expression	1
decabromobiphenyl ether	decreases expression	1
methylparaben	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Acrolein	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Arsenic	increases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012584	Binding	Binding affinity to MON2 protein in human INA-6 cells after 3 hrs by nanoLC-MS/MS method	Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MON2 across ~30M SureChEMBL compounds — explore on Sugi Predict.