MIGA2

Summary

MIGA2 (mitoguardin 2, HGNC:23621) is a protein-coding gene on chromosome 9q34.11, encoding Mitoguardin 2 (Q7L4E1). 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 plasma membrane.

Source: NCBI Gene 84895 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001329990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23621
Approved symbol	MIGA2
Name	mitoguardin 2
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14596, FLJ00199
Ensembl gene	ENSG00000148343
Ensembl biotype	protein_coding
OMIM	616774
Entrez	84895

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 15 protein_coding, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000358369, ENST00000414342, ENST00000439290, ENST00000445183, ENST00000450073, ENST00000471943, ENST00000474534, ENST00000474639, ENST00000477088, ENST00000483458, ENST00000492279, ENST00000494608, ENST00000495975, ENST00000684074, ENST00000885493, ENST00000885494, ENST00000885495, ENST00000885496, ENST00000923055, ENST00000942814, ENST00000942815, ENST00000942816, ENST00000942817, ENST00000942818, ENST00000942819, ENST00000942820

RefSeq mRNA: 2 — MANE Select: NM_001329990 NM_001329990, NM_032809

CCDS: CCDS6917

Canonical transcript exons

ENST00000684074 — 16 exons

Exon	Start	End
ENSE00001238807	129049827	129049963
ENSE00001239368	129049381	129049498
ENSE00001239373	129048427	129048539
ENSE00001955321	129070247	129072082
ENSE00003463759	129059154	129059271
ENSE00003496003	129060550	129060650
ENSE00003519212	129063244	129063316
ENSE00003533317	129042304	129042514
ENSE00003544631	129069076	129069129
ENSE00003578634	129061231	129061346
ENSE00003590117	129063545	129063631
ENSE00003601074	129069849	129069965
ENSE00003618136	129067773	129067871
ENSE00003654796	129068198	129068332
ENSE00003655311	129040452	129040690
ENSE00003918185	129036626	129036681

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4226 / max 81.2498, expressed in 1756 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98871	4.2758	1658
98870	3.1468	1496

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	98.01	gold quality
lower esophagus mucosa	UBERON:0035834	96.63	gold quality
apex of heart	UBERON:0002098	94.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.05	gold quality
cerebellar hemisphere	UBERON:0002245	93.83	gold quality
cerebellar cortex	UBERON:0002129	93.72	gold quality
mucosa of transverse colon	UBERON:0004991	93.20	gold quality
cerebellum	UBERON:0002037	93.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.55	gold quality
transverse colon	UBERON:0001157	92.34	gold quality
left ventricle myocardium	UBERON:0006566	92.13	silver quality
kidney epithelium	UBERON:0004819	91.89	gold quality
granulocyte	CL:0000094	91.81	gold quality
small intestine	UBERON:0002108	91.64	gold quality
upper arm skin	UBERON:0004263	91.40	gold quality
right lobe of thyroid gland	UBERON:0001119	91.37	gold quality
body of stomach	UBERON:0001161	91.22	gold quality
cerebellar vermis	UBERON:0004720	91.06	gold quality
esophagus mucosa	UBERON:0002469	91.02	gold quality
heart left ventricle	UBERON:0002084	90.88	gold quality
right adrenal gland	UBERON:0001233	90.77	gold quality
metanephros cortex	UBERON:0010533	90.71	gold quality
cardiac ventricle	UBERON:0002082	90.69	gold quality
left lobe of thyroid gland	UBERON:0001120	90.63	gold quality
right atrium auricular region	UBERON:0006631	90.56	gold quality
left adrenal gland cortex	UBERON:0035825	90.39	gold quality
cardiac atrium	UBERON:0002081	90.38	gold quality
right adrenal gland cortex	UBERON:0035827	90.16	gold quality
left adrenal gland	UBERON:0001234	90.09	gold quality
esophagus	UBERON:0001043	90.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting MIGA2, 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-9-5P	100.00	72.28	2361
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861

Literature-anchored findings (GeneRIF, showing 1)

• Propose that MIGA1/2 proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD. (PMID:26711011)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	miga2	ENSDARG00000089357
mus_musculus	Miga2	ENSMUSG00000026858
rattus_norvegicus	Miga2	ENSRNOG00000017513
drosophila_melanogaster	Miga	FBGN0030037
caenorhabditis_elegans		WBGENE00010465

Paralogs (1): MIGA1 (ENSG00000180488)

Protein

Protein identifiers

Mitoguardin 2 — Q7L4E1 (reviewed: Q7L4E1)

Alternative names: Protein FAM73B

All UniProt accessions (3): Q7L4E1, B0QZG3, H7C474

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 MIGA1. Interacts with PLD6/MitoPLD. Interacts (via phosphorylated FFAT motif) with MOSPD2, VAPA and VAPB. Interacts with TRABD.

Subcellular location. Mitochondrion outer membrane.

Post-translational modifications. Phosphorylation at Ser-295 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB.

Domain organisation. The FFAT motif is involved in the interaction with MOSPD2, VAPA and VAPB and its phosphorylation regulates these interactions.

Similarity. Belongs to the mitoguardin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7L4E1-1	1	yes
Q7L4E1-2	2
Q7L4E1-3	3

RefSeq proteins (2): NP_001316919, NP_116198 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019392	Miga	Family

Pfam: PF10265

UniProt features (24 total): modified residue 8, splice variant 4, sequence variant 3, transmembrane region 2, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L4E1-F1	66.39	0.33

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 (8): 220, 224, 228, 273, 276, 295, 132, 206

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: 122 (showing top): GOBP_SKELETAL_SYSTEM_DEVELOPMENT, TGCACTT_MIR519C_MIR519B_MIR519A, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_BONE_DEVELOPMENT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_MITOCHONDRIAL_FUSION, VDR_Q3, BURTON_ADIPOGENESIS_5, TTTGCAC_MIR19A_MIR19B, GOBP_ORGANELLE_FUSION, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY

GO Biological Process (2): mitochondrial fusion (GO:0008053), bone development (GO:0060348)

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
skeletal system development	1
animal organ development	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

510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIGA2	VAPA	Q9P0L0	649
MIGA2	STARD3	Q14849	586
MIGA2	PLD6	Q8N2A8	547
MIGA2	RMDN3	Q96TC7	518
MIGA2	MFN2	O95140	501
MIGA2	VPS13D	Q5THJ4	482
MIGA2	PLIN5	Q00G26	448
MIGA2	PRPSAP2	O60256	435
MIGA2	FOXRED1	Q96CU9	430
MIGA2	PET100	P0DJ07	430
MIGA2	OAZ3	Q9UMX2	429
MIGA2	TEKT2	Q9UIF3	422
MIGA2	YBX2	Q9Y2T7	419
MIGA2	DCXR	Q7Z4W1	419
MIGA2	VAPB	O95292	414

IntAct

32 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
MIGA2	SLC27A2	psi-mi:“MI:0914”(association)	0.530
MIGA2	UBB	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
MIGA2	MIGA2	psi-mi:“MI:0915”(physical association)	0.400
MIGA2	MIGA1	psi-mi:“MI:0915”(physical association)	0.400
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.350
SIGLECL1	KIAA1324L	psi-mi:“MI:0914”(association)	0.350
VAPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
VAPB	ESYT2	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	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
HOXC8	ANKRD17	psi-mi:“MI:0914”(association)	0.350
MAGEA9	MED19	psi-mi:“MI:0914”(association)	0.350
MIGA2	UBR4	psi-mi:“MI:0914”(association)	0.350
MTCH1	IPO5	psi-mi:“MI:0914”(association)	0.350
CD80	RIMOC1	psi-mi:“MI:0914”(association)	0.350
PACC1	IPO5	psi-mi:“MI:0914”(association)	0.350
S1PR3	STXBP3	psi-mi:“MI:0914”(association)	0.350
SSTR2	PJA2	psi-mi:“MI:0914”(association)	0.350
SLC27A2	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): FAM73B (Affinity Capture-RNA), FAM73B (Affinity Capture-MS), FAM73B (Affinity Capture-MS), FAM73B (Affinity Capture-MS), FAM73B (Affinity Capture-MS), UBB (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), NIF3L1 (Affinity Capture-MS), SLC27A2 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), FAM73B (Proximity Label-MS), FAM73B (Affinity Capture-RNA), FAM73B (Proximity Label-MS), FAM73B (Affinity Capture-MS)

ESM2 similar proteins: A0A5F9C6I2, A1L3F5, A2BDA5, A3KGS3, A8E4X8, D3ZXK7, F1R7R1, O75129, P21359, P51593, P97526, Q04690, Q1JPG0, Q2PPJ7, Q3SZD5, Q4QQM5, Q4R5A4, Q5RC14, Q5XPI3, Q5XPI4, Q62717, Q66K64, Q6GLR7, Q6NXD8, Q6P4S8, Q6PFH3, Q6VNB8, Q7L4E1, Q7TMY8, Q7Z6Z7, Q80TJ1, Q86UW7, Q8BHR8, Q8BK03, Q8BYR5, Q8CDG3, Q8CF97, Q8CID0, Q8IY22, Q8IZQ1

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3167 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129037014:TGGG:T	donor_loss	1.0000
9:129037015:GG:G	donor_gain	1.0000
9:129037016:GG:G	donor_gain	1.0000
9:129037017:G:A	donor_loss	1.0000
9:129037017:G:GG	donor_gain	1.0000
9:129037018:T:G	donor_loss	1.0000
9:129040493:T:TA	acceptor_gain	1.0000
9:129040494:G:A	acceptor_gain	1.0000
9:129040686:GGCAG:G	donor_gain	1.0000
9:129040687:GCAG:G	donor_gain	1.0000
9:129040687:GCAGG:G	donor_gain	1.0000
9:129040691:G:GG	donor_gain	1.0000
9:129040691:GTA:G	donor_loss	1.0000
9:129040692:T:G	donor_loss	1.0000
9:129042299:TGCA:T	acceptor_loss	1.0000
9:129042300:GCAGT:G	acceptor_loss	1.0000
9:129042301:CAGTC:C	acceptor_loss	1.0000
9:129042302:A:AG	acceptor_gain	1.0000
9:129042302:A:G	acceptor_loss	1.0000
9:129042302:AGTCT:A	acceptor_gain	1.0000
9:129042303:G:GG	acceptor_gain	1.0000
9:129042303:GT:G	acceptor_gain	1.0000
9:129042303:GTC:G	acceptor_gain	1.0000
9:129042303:GTCT:G	acceptor_gain	1.0000
9:129042303:GTCTG:G	acceptor_gain	1.0000
9:129042420:G:GT	donor_gain	1.0000
9:129048422:CACA:C	acceptor_loss	1.0000
9:129048423:ACAG:A	acceptor_gain	1.0000
9:129048424:CA:C	acceptor_loss	1.0000
9:129048425:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000019761 (9:129042852 T>C,G), RS1000086655 (9:129036641 G>A,C,T), RS1000206416 (9:129049005 C>T), RS1000326455 (9:129056569 AG>A), RS1000366260 (9:129044843 G>C), RS1000388724 (9:129054983 C>A), RS1000435223 (9:129062686 A>G), RS1000718642 (9:129040977 G>A), RS1000862783 (9:129052242 C>G,T), RS1000885069 (9:129055329 C>G,T), RS1000889245 (9:129059483 G>T), RS1000941066 (9:129059770 C>T), RS1000992222 (9:129034966 T>C), RS1001117259 (9:129052046 T>G), RS1001175341 (9:129064181 G>A,C)

Disease associations

OMIM: gene MIM:616774 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004102_1	Body mass index (change over time) in lung cancer or chronic obstructive pulmonary disease	1.000000e-07
GCST010143_23	Meat-related diet	6.000000e-11
GCST011494_51	Daytime nap	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement
EFO:0008111	diet measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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