MYG1

Summary

MYG1 (MYG1 exonuclease, HGNC:17590) is a protein-coding gene on chromosome 12q13.13, encoding MYG1 exonuclease (Q9HB07). 3’-5’ RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion.

Enables 3’-5’-RNA exonuclease activity. Involved in mRNA processing; mitochondrial RNA metabolic process; and rRNA processing. Located in mitochondrion and nucleus. Is active in mitochondrial matrix; nucleolus; and nucleoplasm.

Source: NCBI Gene 60314 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_021640

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17590
Approved symbol	MYG1
Name	MYG1 exonuclease
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	MYG, Gamm1
Ensembl gene	ENSG00000139637
Ensembl biotype	protein_coding
OMIM	611366
Entrez	60314

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 6 retained_intron

ENST00000267103, ENST00000547490, ENST00000547864, ENST00000548632, ENST00000548845, ENST00000549177, ENST00000549488, ENST00000550199, ENST00000551131, ENST00000551670, ENST00000924327, ENST00000924328

RefSeq mRNA: 1 — MANE Select: NM_021640 NM_021640

CCDS: CCDS31810

Canonical transcript exons

ENST00000267103 — 7 exons

Exon	Start	End
ENSE00000939398	53299695	53299953
ENSE00002340221	53306966	53307177
ENSE00003486130	53303034	53303193
ENSE00003517790	53306198	53306320
ENSE00003577675	53306680	53306861
ENSE00003686585	53300150	53300262
ENSE00003756604	53305908	53306060

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 96.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.0808 / max 340.5692, expressed in 1758 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125738	29.7737	1750
125739	5.0966	1583
125742	2.8066	1232
125740	0.8371	542
125741	0.4177	223
125743	0.1490	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	96.81	gold quality
right testis	UBERON:0004534	96.79	gold quality
left testis	UBERON:0004533	96.78	gold quality
testis	UBERON:0000473	96.15	gold quality
hypothalamus	UBERON:0001898	95.73	gold quality
prefrontal cortex	UBERON:0000451	95.34	gold quality
substantia nigra	UBERON:0002038	95.04	gold quality
superior frontal gyrus	UBERON:0002661	94.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.90	gold quality
frontal cortex	UBERON:0001870	94.89	gold quality
frontal lobe	UBERON:0016525	94.89	gold quality
anterior cingulate cortex	UBERON:0009835	94.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.77	gold quality
cerebral cortex	UBERON:0000956	94.74	gold quality
temporal lobe	UBERON:0001871	94.63	gold quality
amygdala	UBERON:0001876	94.63	gold quality
Ammon’s horn	UBERON:0001954	94.60	gold quality
right frontal lobe	UBERON:0002810	94.39	gold quality
nucleus accumbens	UBERON:0001882	94.21	gold quality
putamen	UBERON:0001874	93.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.78	gold quality
brain	UBERON:0000955	93.73	gold quality
caudate nucleus	UBERON:0001873	93.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.81	gold quality
adenohypophysis	UBERON:0002196	92.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.59	gold quality
pituitary gland	UBERON:0000007	92.52	gold quality
left adrenal gland cortex	UBERON:0035825	92.46	gold quality
left adrenal gland	UBERON:0001234	92.29	gold quality
mucosa of transverse colon	UBERON:0004991	92.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.63
E-MTAB-9689	no	101.27

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• demonstrates possible role of MYG1 in vitiligo (PMID:16996721)
• Human and mouse MYG1 is ubiquitously expressed, with the highest level in the testis. (PMID:19014353)
• Both MYG1 promoter polymorphism and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have an impact on the regulation of the MYG1 gene and promoter polymorphism is related with suspectibility for actively progressing vitiligo. (PMID:20377893)
• Significant increase in MYG1 mRNA expression was observed in vitiligo patients compared to controls. The MYG1 mRNA expression was increased in patients with active and generalized vitiligo as compared to stable and localized vitiligo. (PMID:23706493)
• analysis of the widely conserved dually localized protein Myg1 shows that it has a role as a 3’-5’ RNA exonuclease (PMID:31081026)
• MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration. (PMID:38862489)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	myg1	ENSDARG00000069977
mus_musculus	Myg1	ENSMUSG00000001285
rattus_norvegicus	Myg1	ENSRNOG00000013343
drosophila_melanogaster	CG11980	FBGN0037652
caenorhabditis_elegans		WBGENE00007787

Protein

Protein identifiers

MYG1 exonuclease — Q9HB07 (reviewed: Q9HB07)

All UniProt accessions (4): Q9HB07, F8VQQ3, F8VR84, H3BPH3

UniProt curated annotations — full annotation on UniProt →

Function. 3’-5’ RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion. Involved in regulating spatially segregated organellar RNA processing, acts as a coordinator of nucleo-mitochondrial crosstalk. In nucleolus, processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, processes 3’-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins.

Subcellular location. Nucleus. Nucleoplasm. Mitochondrion matrix. Nucleolus.

Tissue specificity. Ubiquitously expressed, with highest levels in testis.

Disease relevance. Several works have found that mRNA expression is elevated in the skin of vitiligo patients.

Similarity. Belongs to the MYG1 family.

RefSeq proteins (1): NP_067653* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003226	MYG1_exonuclease	Family

Pfam: PF03690

UniProt features (11 total): modified residue 3, sequence conflict 2, sequence variant 2, mutagenesis site 2, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
24AN	X-RAY DIFFRACTION	1.76
24AP	X-RAY DIFFRACTION	1.78
24BD	X-RAY DIFFRACTION	1.78
24AO	X-RAY DIFFRACTION	1.81
24BL	X-RAY DIFFRACTION	1.81
24BW	X-RAY DIFFRACTION	1.82
24AJ	X-RAY DIFFRACTION	1.83
24AQ	X-RAY DIFFRACTION	1.84
24AW	X-RAY DIFFRACTION	1.86
24BZ	X-RAY DIFFRACTION	1.91
24BU	X-RAY DIFFRACTION	1.93
24CA	X-RAY DIFFRACTION	1.93
24BS	X-RAY DIFFRACTION	2
24BX	X-RAY DIFFRACTION	2.01
24BR	X-RAY DIFFRACTION	2.1
24AY	X-RAY DIFFRACTION	2.12
24BP	X-RAY DIFFRACTION	2.2
24BQ	X-RAY DIFFRACTION	2.3
24BM	X-RAY DIFFRACTION	2.31
24BV	X-RAY DIFFRACTION	2.45
24AH	X-RAY DIFFRACTION	2.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HB07-F1	89.86	0.83

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): 120, 267, 273

Mutagenesis-validated functional residues (2):

Position	Phenotype
106–108	catalytically inactive.
344	loss of rnase activity and gained single stranded dnase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_RIBOSOME_BIOGENESIS, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_BEHAVIOR, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, CHANDRAN_METASTASIS_DN, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GOBP_EXPLORATION_BEHAVIOR, GOMF_EXONUCLEASE_ACTIVITY, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_LOCOMOTORY_EXPLORATION_BEHAVIOR, GOCC_MITOCHONDRIAL_MATRIX

GO Biological Process (4): mitochondrial RNA metabolic process (GO:0000959), rRNA processing (GO:0006364), mRNA processing (GO:0006397), locomotory exploration behavior (GO:0035641)

GO Molecular Function (4): 3’-5’-RNA exonuclease activity (GO:0000175), nuclease activity (GO:0004518), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
RNA processing	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cellular anatomical structure	2
RNA metabolic process	1
rRNA metabolic process	1
ribosome biogenesis	1
mRNA metabolic process	1
locomotory behavior	1
exploration behavior	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYG1	SLC61A1	Q6N075	613
MYG1	PFDN5	Q99471	590
MYG1	CSTPP1	Q9H6J7	505
MYG1	KPRP	Q5T749	475
MYG1	ZNF408	Q9H9D4	461
MYG1	ESPL1	Q14674	430
MYG1	TRMT13	Q9NUP7	416
MYG1	RARG	P13631	410
MYG1	GPALPP1	Q8IXQ4	406
MYG1	EIF6	P56537	398
MYG1	ARHGAP1	Q07960	398
MYG1	ADRA1D	P25100	383
MYG1	RTCA	O00442	365
MYG1	TXNDC5	Q8NBS9	360
MYG1	LRRC3	Q9BY71	357

IntAct

157 interactions, top by confidence:

A	B	Type	Score
ARL6IP1	MYG1	psi-mi:“MI:0915”(physical association)	0.720
MYG1	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
MYG1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.670
FAM9B	MYG1	psi-mi:“MI:0915”(physical association)	0.670
CMTM5	MYG1	psi-mi:“MI:0915”(physical association)	0.670
MYG1	CMTM5	psi-mi:“MI:0915”(physical association)	0.670
MYG1	FAM9B	psi-mi:“MI:0915”(physical association)	0.670
AGTRAP	MYG1	psi-mi:“MI:0915”(physical association)	0.670
MYG1	TMEM239	psi-mi:“MI:0915”(physical association)	0.560
TMEM239	MYG1	psi-mi:“MI:0915”(physical association)	0.560
	MYG1	psi-mi:“MI:0915”(physical association)	0.560
MYG1	REEP6	psi-mi:“MI:0915”(physical association)	0.560
MYG1	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
MYG1	MAL2	psi-mi:“MI:0915”(physical association)	0.560
MYG1	ROM1	psi-mi:“MI:0915”(physical association)	0.560
MYG1	TIMM17B	psi-mi:“MI:0915”(physical association)	0.560

ESM2 similar proteins: A0JNU3, A2RRV9, A4FV58, A7SDA8, A8WH18, B0WU52, B3N018, B3NKH7, B4GXC8, B4IMH3, B4ISL0, B4JBE6, B4KFU7, B4LQR5, B4MUM8, B4NSS7, B5DK31, D3ZX08, O88202, O93610, P51178, P51687, Q16ML2, Q2YDU6, Q3UQ84, Q58DG1, Q5BK18, Q5JTZ9, Q5RCH4, Q5RF36, Q5ZKI2, Q641W2, Q68FW7, Q6DE00, Q6DHP6, Q6GP25, Q75E78, Q7PWB8, Q7TMW6, Q86U10

Diamond homologs: O17606, P40093, Q55G91, Q58DG1, Q641W2, Q9HB07, Q9JK81, Q9P7T6, O84391, Q9PK08, Q9Z862

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

740 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53300260:GAG:G	donor_gain	1.0000
12:53300261:AG:A	donor_gain	1.0000
12:53300261:AGGTA:A	donor_loss	1.0000
12:53300262:GG:G	donor_gain	1.0000
12:53300262:GGTA:G	donor_loss	1.0000
12:53300263:G:GG	donor_gain	1.0000
12:53300263:GTAG:G	donor_loss	1.0000
12:53303032:AG:A	acceptor_gain	1.0000
12:53303033:G:A	acceptor_loss	1.0000
12:53303033:GG:G	acceptor_gain	1.0000
12:53303033:GGT:G	acceptor_gain	1.0000
12:53303033:GGTCT:G	acceptor_gain	1.0000
12:53305907:GAT:G	acceptor_gain	1.0000
12:53306061:G:GG	donor_gain	1.0000
12:53306062:T:A	donor_loss	1.0000
12:53306197:G:GT	acceptor_gain	1.0000
12:53306197:GGCA:G	acceptor_gain	1.0000
12:53306826:G:GG	donor_gain	1.0000
12:53306858:GCCG:G	donor_gain	1.0000
12:53302417:T:A	acceptor_gain	0.9900
12:53303032:A:AG	acceptor_gain	0.9900
12:53303033:G:GA	acceptor_gain	0.9900
12:53303033:GGTC:G	acceptor_gain	0.9900
12:53303168:GCATG:G	donor_gain	0.9900
12:53303191:AAGGT:A	donor_loss	0.9900
12:53303192:AGGTG:A	donor_loss	0.9900
12:53303193:GGTGG:G	donor_loss	0.9900
12:53303195:T:A	donor_loss	0.9900
12:53305900:T:A	acceptor_gain	0.9900
12:53305906:A:AG	acceptor_gain	0.9900

AlphaMissense

2427 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53299885:C:G	H50D	0.997
12:53299897:T:C	F54L	0.997
12:53299899:C:A	F54L	0.997
12:53299899:C:G	F54L	0.997
12:53300211:A:T	D93V	0.997
12:53306204:T:C	F217L	0.997
12:53306206:C:A	F217L	0.997
12:53306206:C:G	F217L	0.997
12:53300251:C:A	D106E	0.996
12:53300251:C:G	D106E	0.996
12:53303038:T:C	F112L	0.996
12:53303040:C:A	F112L	0.996
12:53303040:C:G	F112L	0.996
12:53303095:A:C	S131R	0.996
12:53303097:T:A	S131R	0.996
12:53303097:T:G	S131R	0.996
12:53306205:T:C	F217S	0.996
12:53299887:C:A	H50Q	0.995
12:53299887:C:G	H50Q	0.995
12:53299910:A:T	E58V	0.995
12:53300212:C:A	D93E	0.995
12:53300212:C:G	D93E	0.995
12:53307060:T:C	F348L	0.995
12:53307062:C:A	F348L	0.995
12:53307062:C:G	F348L	0.995
12:53299885:C:A	H50N	0.994
12:53300210:G:C	D93H	0.994
12:53300211:A:C	D93A	0.994
12:53300250:A:T	D106V	0.994
12:53300244:G:C	R104P	0.993

dbSNP variants (sampled 300 via entrez): RS1000296648 (12:53300672 C>T), RS1000327419 (12:53300418 G>A,C), RS1000551468 (12:53305229 A>C), RS1000588670 (12:53306659 G>C), RS1000658582 (12:53299549 T>C), RS1000872246 (12:53297837 T>C), RS1001600949 (12:53305730 A>G), RS1001644224 (12:53306277 C>T), RS1001868497 (12:53304704 C>T), RS1002146273 (12:53299013 G>C), RS1002159135 (12:53298887 G>A), RS1003212322 (12:53297895 G>A), RS1003286789 (12:53299148 A>G), RS1003292900 (12:53307122 G>A), RS1003623159 (12:53303315 A>G)

Disease associations

OMIM: gene MIM:611366 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	affects expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
calfactant	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Acetaminophen	decreases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Diethylstilbestrol	decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1
Nanotubes, Carbon	affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1Y0	Abcam HeLa MYG1 KO	Cancer cell line	Female
CVCL_SG00	HAP1 C12orf10 (-) 1	Cancer cell line	Male
CVCL_XM16	HAP1 C12orf10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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