MIGA1

Summary

MIGA1 (mitoguardin 1, HGNC:24741) is a protein-coding gene on chromosome 1p31.1, encoding Mitoguardin 1 (Q8NAN2). Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers.

Enables protein heterodimerization activity and protein homodimerization activity. Involved in mitochondrial fusion. Located in mitochondrion and plasma membrane.

Source: NCBI Gene 374986 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_001416120

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24741
Approved symbol	MIGA1
Name	mitoguardin 1
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35093
Ensembl gene	ENSG00000180488
Ensembl biotype	protein_coding
OMIM	616773
Entrez	374986

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 33 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000370791, ENST00000443751, ENST00000476203, ENST00000642959, ENST00000643143, ENST00000643390, ENST00000645526, ENST00000645756, ENST00000646892, ENST00000710931, ENST00000710932, ENST00000881008, ENST00000881009, ENST00000881010, ENST00000881011, ENST00000881012, ENST00000881013, ENST00000881014, ENST00000881015, ENST00000881016, ENST00000881017, ENST00000881018, ENST00000966498, ENST00000966499, ENST00000966500, ENST00000966501, ENST00000966502, ENST00000966503, ENST00000966504, ENST00000966505, ENST00000966506, ENST00000966507, ENST00000966508, ENST00000966509, ENST00000966510

RefSeq mRNA: 17 — MANE Select: NM_001416120 NM_001270384, NM_001363583, NM_001363584, NM_001363586, NM_001394566, NM_001394567, NM_001394568, NM_001394569, NM_001394570, NM_001394571, NM_001394572, NM_001394573, NM_001394574, NM_001394575, NM_001394576, NM_001416120, NM_198549

CCDS: CCDS681, CCDS85989, CCDS90981

Canonical transcript exons

ENST00000370791 — 16 exons

Exon	Start	End
ENSE00001213305	77873004	77873120
ENSE00001213312	77866338	77866391
ENSE00001213323	77863894	77864028
ENSE00001213330	77861224	77861322
ENSE00001213339	77860040	77860126
ENSE00001213347	77859314	77859386
ENSE00001213351	77858938	77859056
ENSE00001213393	77803270	77803406
ENSE00001213403	77801331	77801508
ENSE00001453638	77874846	77879540
ENSE00003530817	77815108	77815231
ENSE00003532968	77813734	77813867
ENSE00003534830	77843307	77843407
ENSE00003548165	77806975	77807101
ENSE00003674630	77783238	77783351
ENSE00003926509	77779649	77779736

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.4680 / max 1085.4831, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3610	33.9993	1814
3612	0.8366	408
3611	0.6321	314

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	96.66	gold quality
endothelial cell	CL:0000115	96.44	gold quality
substantia nigra pars compacta	UBERON:0001965	94.73	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.14	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.92	gold quality
epithelial cell of pancreas	CL:0000083	93.12	gold quality
pons	UBERON:0000988	92.33	gold quality
subthalamic nucleus	UBERON:0001906	91.96	gold quality
inferior vagus X ganglion	UBERON:0005363	91.93	gold quality
lateral globus pallidus	UBERON:0002476	91.88	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.64	gold quality
corpus callosum	UBERON:0002336	91.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.29	gold quality
medulla oblongata	UBERON:0001896	90.48	gold quality
superior vestibular nucleus	UBERON:0007227	90.45	gold quality
dorsal root ganglion	UBERON:0000044	89.57	gold quality
occipital lobe	UBERON:0002021	89.57	gold quality
primary visual cortex	UBERON:0002436	89.33	gold quality
calcaneal tendon	UBERON:0003701	89.11	gold quality
ventral tegmental area	UBERON:0002691	88.70	gold quality
cerebellar vermis	UBERON:0004720	87.25	gold quality
trigeminal ganglion	UBERON:0001675	87.14	gold quality
prefrontal cortex	UBERON:0000451	86.94	gold quality
globus pallidus	UBERON:0001875	86.49	gold quality
entorhinal cortex	UBERON:0002728	86.45	gold quality
islet of Langerhans	UBERON:0000006	86.30	gold quality
tibialis anterior	UBERON:0001385	86.07	gold quality
ileal mucosa	UBERON:0000331	85.95	gold quality
germinal epithelium of ovary	UBERON:0001304	85.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

224 targeting MIGA1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593

Literature-anchored findings (GeneRIF, showing 1)

• Propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD. (PMID:26711011)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	miga1	ENSDARG00000020596
mus_musculus	Miga1	ENSMUSG00000054942
rattus_norvegicus	Miga1	ENSRNOG00000056332
drosophila_melanogaster	Miga	FBGN0030037
caenorhabditis_elegans		WBGENE00010465

Paralogs (1): MIGA2 (ENSG00000148343)

Protein

Protein identifiers

Mitoguardin 1 — Q8NAN2 (reviewed: Q8NAN2)

Alternative names: Protein FAM73A

All UniProt accessions (7): A0A2R8YDC7, A0A2R8YF99, A0A2R8YFQ8, A0A2R8YGK2, A0AA34QW11, Q8NAN2, F8W7S1

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD.

Subunit / interactions. Homodimer and heterodimer; forms heterodimers with MIGA2. Interacts with PLD6/MitoPLD.

Subcellular location. Mitochondrion outer membrane.

Similarity. Belongs to the mitoguardin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NAN2-1	1	yes
Q8NAN2-2	2

RefSeq proteins (17): NP_001257313, NP_001350512, NP_001350513, NP_001350515, NP_001381495, NP_001381496, NP_001381497, NP_001381498, NP_001381499, NP_001381500, NP_001381501, NP_001381502, NP_001381503, NP_001381504, NP_001381505, NP_001403049, NP_940951 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019392	Miga	Family

Pfam: PF10265

UniProt features (6 total): modified residue 2, splice variant 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9JCW	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAN2-F1	65.38	0.39

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 (2): 289, 293

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA
R-HSA-1430728	Metabolism
R-HSA-1483206	Glycerophospholipid biosynthesis
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 167 (showing top): GOCC_MITOCHONDRIAL_ENVELOPE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_MITOCHONDRIAL_FUSION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, BASAKI_YBX1_TARGETS_DN, GOBP_ORGANELLE_FUSION, NUYTTEN_EZH2_TARGETS_DN, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, GOCC_ORGANELLE_ENVELOPE, LU_EZH2_TARGETS_DN, JOHNSTONE_PARVB_TARGETS_3_DN

GO Biological Process (1): mitochondrial fusion (GO:0008053)

GO Molecular Function (3): protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein dimerization activity	2
mitochondrion organization	1
organelle fusion	1
identical protein binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIGA1	PLD6	Q8N2A8	582
MIGA1	PIGA	P37287	560
MIGA1	PIGR	P01833	507
MIGA1	MFSD6	Q6ZSS7	487
MIGA1	JCHAIN	P01591	486
MIGA1	ADGRL4	Q9HBW9	475
MIGA1	ZZZ3	Q8IYH5	458
MIGA1	FCAR	P24071	448
MIGA1	CSGALNACT2	Q8N6G5	444
MIGA1	UHMK1	Q8TAS1	427
MIGA1	PAK1IP1	Q9NWT1	414
MIGA1	AK5	Q9Y6K8	409
MIGA1	GIPC2	Q8TF65	408
MIGA1	AK9	Q5TCS8	400
MIGA1	MSTO1	Q9BUK6	380

IntAct

41 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
ERP44	MEX3A	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
ZAR1L	BCL2L11	psi-mi:“MI:0914”(association)	0.530
MIGA1	MIGA1	psi-mi:“MI:0915”(physical association)	0.400
MIGA2	MIGA1	psi-mi:“MI:0915”(physical association)	0.400
MIGA1		psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
GYPA	HYKK	psi-mi:“MI:0914”(association)	0.350
EFNB1	KRBA1	psi-mi:“MI:0914”(association)	0.350
NCR3LG1	PEDS1	psi-mi:“MI:0914”(association)	0.350
SIGLECL1	RBFOX3	psi-mi:“MI:0914”(association)	0.350
BTNL9	GPR89A	psi-mi:“MI:0914”(association)	0.350
PACC1	TNPO2	psi-mi:“MI:0914”(association)	0.350
P2RX5	TNPO2	psi-mi:“MI:0914”(association)	0.350
CHRM4	TNPO2	psi-mi:“MI:0914”(association)	0.350
FZD10	TNPO2	psi-mi:“MI:0914”(association)	0.350
CLEC2B	DEGS1	psi-mi:“MI:0914”(association)	0.350
APOBEC3DE	CASC3	psi-mi:“MI:0914”(association)	0.350
TMEM126A	IPO7	psi-mi:“MI:0914”(association)	0.350
ZNF555	HERC1	psi-mi:“MI:0914”(association)	0.350
COMTD1	TNPO2	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Affinity Capture-MS), FAM73A (Proximity Label-MS)

ESM2 similar proteins: A0A0D3MU35, A0A0D3MU50, A2T1U1, B9DHG0, B9F4I8, E5KCJ8, F4HZK4, F4I933, F4J117, F4JLC1, M1C5M7, P10349, Q2QTC2, Q39639, Q3UD82, Q42463, Q4QQM5, Q53NI2, Q5N800, Q67Y99, Q7SZC5, Q7Y220, Q8H0W0, Q8NAN2, Q8RWG3, Q8VYD8, Q8VYL1, Q8W4K5, Q93YW0, Q940U6, Q944I4, Q94AX2, Q94CJ5, Q9C4Z7, Q9C5W3, Q9C642, Q9FEQ0, Q9FIG9, Q9FKF4, Q9FMX6

Diamond homologs: Q1JPG0, Q4QQM5, Q5BLE2, Q5XJS0, Q6GR21, Q6NRB7, Q7L4E1, Q8BK03, Q8NAN2, Q9W3F7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3183 predictions. Top by Δscore:

Variant	Effect	Δscore
1:77779732:TCCAG:T	donor_loss	1.0000
1:77779733:CCAGG:C	donor_loss	1.0000
1:77779734:CAGG:C	donor_loss	1.0000
1:77779735:AGG:A	donor_loss	1.0000
1:77779736:GGTA:G	donor_loss	1.0000
1:77779737:GT:G	donor_loss	1.0000
1:77779738:T:G	donor_loss	1.0000
1:77783231:A:AG	acceptor_gain	1.0000
1:77801314:AACT:A	acceptor_gain	1.0000
1:77801507:AG:A	donor_loss	1.0000
1:77801508:GG:G	donor_loss	1.0000
1:77801509:G:A	donor_loss	1.0000
1:77801509:GT:G	donor_gain	1.0000
1:77803402:CCTCT:C	donor_gain	1.0000
1:77803403:CTCT:C	donor_gain	1.0000
1:77803403:CTCTG:C	donor_loss	1.0000
1:77803404:TCT:T	donor_gain	1.0000
1:77803404:TCTGT:T	donor_loss	1.0000
1:77803405:CT:C	donor_gain	1.0000
1:77803405:CTGT:C	donor_loss	1.0000
1:77803406:TG:T	donor_loss	1.0000
1:77803407:G:GG	donor_gain	1.0000
1:77803408:TAA:T	donor_loss	1.0000
1:77803409:A:AC	donor_loss	1.0000
1:77803410:AGT:A	donor_loss	1.0000
1:77803411:G:C	donor_loss	1.0000
1:77813728:TTTTA:T	acceptor_loss	1.0000
1:77813729:TTTA:T	acceptor_loss	1.0000
1:77813730:TTA:T	acceptor_loss	1.0000
1:77813731:TAGGT:T	acceptor_loss	1.0000

AlphaMissense

4173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:77813766:T:A	W224R	1.000
1:77813766:T:C	W224R	1.000
1:77807101:G:C	G213R	0.999
1:77813767:G:C	W224S	0.999
1:77813768:G:C	W224C	0.999
1:77813768:G:T	W224C	0.999
1:77859361:T:C	L388P	0.999
1:77807101:G:T	G213C	0.998
1:77813734:G:A	G213D	0.998
1:77813754:G:C	A220P	0.998
1:77813775:G:C	A227P	0.998
1:77815151:T:C	L272P	0.998
1:77815169:T:C	L278P	0.998
1:77859373:G:C	R392P	0.998
1:77861309:T:C	L454P	0.998
1:77864022:A:C	K501N	0.998
1:77864022:A:T	K501N	0.998
1:77859355:C:A	A386D	0.997
1:77866339:C:A	A504D	0.997
1:77807092:T:G	Y210D	0.996
1:77813734:G:T	G213V	0.996
1:77813776:C:A	A227D	0.996
1:77813779:T:C	L228P	0.996
1:77859348:T:C	F384L	0.996
1:77859350:T:A	F384L	0.996
1:77859350:T:G	F384L	0.996
1:77864002:T:A	W495R	0.996
1:77864002:T:C	W495R	0.996
1:77815139:T:C	L268P	0.995
1:77815148:T:C	L271P	0.995

dbSNP variants (sampled 300 via entrez): RS1000000914 (1:77867608 G>A,C,T), RS1000004897 (1:77866083 T>A), RS1000005483 (1:77778690 GTTTT>G,GTTTTT), RS1000073221 (1:77848391 A>G), RS1000080710 (1:77874217 G>A,T), RS1000084662 (1:77790976 CAGT>C), RS1000097739 (1:77855458 T>C), RS1000173019 (1:77836188 A>G), RS1000293982 (1:77794813 A>G), RS1000303216 (1:77854448 C>G), RS1000307695 (1:77840335 G>A), RS1000317623 (1:77802275 G>C), RS1000335092 (1:77866283 A>G), RS1000350394 (1:77802659 C>T), RS1000367897 (1:77861410 G>A,C)

Disease associations

OMIM: gene MIM:616773 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003264_764	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST004744_62	Lung adenocarcinoma	3.000000e-07
GCST004748_65	Lung cancer	4.000000e-06
GCST008362_139	Birth weight	2.000000e-08
GCST010063_4	Physiological traits	9.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0004344	birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, affects cotreatment	3
Valproic Acid	affects cotreatment, decreases expression, increases expression	3
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases 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	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression, increases abundance	1
Estradiol	increases expression	1
Formaldehyde	increases expression	1
Mercuric Chloride	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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