MAIP1

Summary

MAIP1 (matrix AAA peptidase interacting protein 1, HGNC:26198) is a protein-coding gene on chromosome 2q33.1, encoding m-AAA protease-interacting protein 1, mitochondrial (Q8WWC4). Promotes sorting of SMDT1/EMRE in mitochondria by ensuring its maturation.

Predicted to enable ribosome binding activity. Involved in calcium import into the mitochondrion; mitochondrial calcium ion homeostasis; and protein insertion into mitochondrial membrane. Located in mitochondrial matrix.

Source: NCBI Gene 79568 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_001394955

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26198
Approved symbol	MAIP1
Name	matrix AAA peptidase interacting protein 1
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp666A212, FLJ22555
Ensembl gene	ENSG00000162972
Ensembl biotype	protein_coding
OMIM	617267
Entrez	79568

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000295079, ENST00000392290, ENST00000435773, ENST00000469156

RefSeq mRNA: 3 — MANE Select: NM_001394955 NM_001369399, NM_001394955, NM_024520

CCDS: CCDS2329

Canonical transcript exons

ENST00000392290 — 5 exons

Exon	Start	End
ENSE00001070239	199961781	199961928
ENSE00001070240	199959268	199959339
ENSE00001511326	199963733	199964117
ENSE00001511327	199955582	199956248
ENSE00003583782	199959754	199959880

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 93.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.5008 / max 108.5483, expressed in 1811 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24525	17.9634	1809
24523	1.1657	707
24526	0.7712	515
24524	0.6005	344

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	93.82	gold quality
nephron tubule	UBERON:0001231	93.63	gold quality
parotid gland	UBERON:0001831	92.74	gold quality
oocyte	CL:0000023	92.56	gold quality
secondary oocyte	CL:0000655	92.53	gold quality
vastus lateralis	UBERON:0001379	92.09	gold quality
liver	UBERON:0002107	91.98	gold quality
jejunum	UBERON:0002115	91.80	gold quality
quadriceps femoris	UBERON:0001377	91.73	gold quality
kidney epithelium	UBERON:0004819	91.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.51	gold quality
colonic mucosa	UBERON:0000317	91.42	gold quality
calcaneal tendon	UBERON:0003701	91.40	gold quality
duodenum	UBERON:0002114	91.24	gold quality
biceps brachii	UBERON:0001507	91.16	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.10	gold quality
right lobe of liver	UBERON:0001114	90.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.65	gold quality
mucosa of transverse colon	UBERON:0004991	90.37	gold quality
palpebral conjunctiva	UBERON:0001812	90.26	gold quality
renal medulla	UBERON:0000362	90.19	gold quality
body of tongue	UBERON:0011876	90.12	gold quality
deltoid	UBERON:0001476	90.10	gold quality
renal glomerulus	UBERON:0000074	90.02	gold quality
metanephric glomerulus	UBERON:0004736	89.93	gold quality
adult mammalian kidney	UBERON:0000082	89.71	gold quality
triceps brachii	UBERON:0001509	89.68	gold quality
heart right ventricle	UBERON:0002080	89.54	gold quality
skeletal muscle tissue	UBERON:0001134	89.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting MAIP1, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548N	99.98	71.94	4170
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-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 1)

• miR-27b targets MAIP1 to mediate lipid accumulation in cultured human and mouse hepatic cells. (PMID:37355744)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	maip1	ENSDARG00000069671
mus_musculus	Maip1	ENSMUSG00000025971
rattus_norvegicus	Maip1	ENSRNOG00000015983
drosophila_melanogaster	CG3776	FBGN0035088
caenorhabditis_elegans		WBGENE00044745

Protein

Protein identifiers

m-AAA protease-interacting protein 1, mitochondrial — Q8WWC4 (reviewed: Q8WWC4)

Alternative names: Matrix AAA peptidase-interacting protein 1

All UniProt accessions (2): Q8WWC4, H7C0V0

UniProt curated annotations — full annotation on UniProt →

Function. Promotes sorting of SMDT1/EMRE in mitochondria by ensuring its maturation. Interacts with the transit peptide region of SMDT1/EMRE precursor protein in the mitochondrial matrix, leading to protect it against protein degradation by YME1L1, thereby ensuring SMDT1/EMRE maturation by the mitochondrial processing peptidase (PMPCA and PMPCB).

Subunit / interactions. Interacts with AFG3L2. Interacts with SPG7. Interacts with SMDT1/EMRE (via the N-terminal transit peptide); interaction is direct and takes place before maturation of SMDT1/EMRE.

Subcellular location. Mitochondrion matrix.

RefSeq proteins (3): NP_001356328, NP_001381884, NP_078796 (=MANE)

Domains & families (InterPro)

UniProt features (4 total): transit peptide 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWC4-F1	68.20	0.37

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8949664	Processing of SMDT1
R-HSA-382551	Transport of small molecules
R-HSA-8949215	Mitochondrial calcium ion transport

MSigDB gene sets: 143 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, TSENG_IRS1_TARGETS_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MITOCHONDRIAL_CALCIUM_ION_HOMEOSTASIS, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT

GO Biological Process (4): protein insertion into mitochondrial inner membrane from matrix (GO:0032979), calcium import into the mitochondrion (GO:0036444), protein insertion into mitochondrial membrane (GO:0051204), mitochondrial calcium ion homeostasis (GO:0051560)

GO Molecular Function (2): ribosome binding (GO:0043022), protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Mitochondrial calcium ion transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
inner mitochondrial membrane organization	1
protein insertion into mitochondrial membrane	1
mitochondrial calcium ion transmembrane transport	1
intercellular transport	1
mitochondrial membrane organization	1
protein insertion into membrane	1
establishment of localization in cell	1
protein localization to mitochondrion	1
establishment of protein localization to organelle	1
intracellular calcium ion homeostasis	1
ribonucleoprotein complex binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAIP1	RMP64	Q6NW34	574
MAIP1	SMDT1	Q9H4I9	572
MAIP1	STOX2	Q9P2F5	559
MAIP1	ARHGAP42	A6NI28	521
MAIP1	FBXO21	O94952	506
MAIP1	PRSS56	P0CW18	496
MAIP1	ASCL4	Q6XD76	494
MAIP1	MEIOC	A2RUB1	491
MAIP1	UVSSA	Q2YD98	474
MAIP1	EIF2S2	P20042	458
MAIP1	AFG3L2	Q9Y4W6	445
MAIP1	ABCA12	Q86UK0	438
MAIP1	MTFR1L	Q9H019	430
MAIP1	NSMCE4A	Q9NXX6	426
MAIP1	MICOS13	Q5XKP0	419

IntAct

74 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
MAIP1	APOC4	psi-mi:“MI:0915”(physical association)	0.560
MAIP1	H4C7	psi-mi:“MI:0915”(physical association)	0.560
APOC1	MAIP1	psi-mi:“MI:0915”(physical association)	0.560
APOC4	MAIP1	psi-mi:“MI:0915”(physical association)	0.560
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
Tubb4b	MGST3	psi-mi:“MI:0915”(physical association)	0.400
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
TUBA1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
HA	ESYT2	psi-mi:“MI:0914”(association)	0.350
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAD2L2		psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6		psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350

BioGRID (113): C2orf47 (Affinity Capture-MS), C2orf47 (Affinity Capture-MS), C2orf47 (Affinity Capture-MS), C2orf47 (Affinity Capture-MS), C2orf47 (Affinity Capture-MS), SPG7 (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), CPS1 (Affinity Capture-MS), C2orf47 (Affinity Capture-MS), CPT2 (Affinity Capture-MS), CLPB (Affinity Capture-MS), PMPCB (Affinity Capture-MS), PMPCA (Affinity Capture-MS), SFXN4 (Affinity Capture-MS)

ESM2 similar proteins: A3KN05, A4IG66, B5DFG1, D3Z8X7, D4A4K3, O35144, O75182, P0DKR2, P82649, P82650, Q15554, Q28C41, Q3SZV6, Q3V0L5, Q5F479, Q5PPN7, Q5R8S0, Q5REP2, Q5RFI6, Q5TC12, Q5U2X7, Q6AY04, Q6IRU7, Q6P1H6, Q6PCG6, Q6ZNE5, Q7L8L6, Q7TP65, Q811I0, Q86XL3, Q8BHE8, Q8BM55, Q8C008, Q8CDJ3, Q8K1S6, Q8N163, Q8N9B5, Q8TF30, Q8VDP4, Q8WWC4

Diamond homologs: A3KN05, Q6AY04, Q8BHE8, Q8WWC4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional regulation of granulopoiesis	5	13.9×	8e-03
Signaling by Nuclear Receptors	5	11.3×	8e-03
Factors involved in megakaryocyte development and platelet production	6	8.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1166 predictions. Top by Δscore:

Variant	Effect	Δscore
2:199956237:G:GT	donor_gain	1.0000
2:199956244:AGCAG:A	donor_loss	1.0000
2:199956246:CAGGT:C	donor_loss	1.0000
2:199956247:AGGT:A	donor_loss	1.0000
2:199956248:GG:G	donor_loss	1.0000
2:199956249:G:C	donor_loss	1.0000
2:199956250:T:G	donor_loss	1.0000
2:199959266:A:G	acceptor_gain	1.0000
2:199959749:CTTA:C	acceptor_loss	1.0000
2:199959750:TTA:T	acceptor_loss	1.0000
2:199959751:TAG:T	acceptor_loss	1.0000
2:199959752:AGGTG:A	acceptor_loss	1.0000
2:199959753:G:GC	acceptor_loss	1.0000
2:199958818:A:AG	acceptor_gain	0.9900
2:199959262:TTCAA:T	acceptor_loss	0.9900
2:199959263:TCAA:T	acceptor_loss	0.9900
2:199959264:CAA:C	acceptor_loss	0.9900
2:199959265:A:AG	acceptor_gain	0.9900
2:199959265:AAG:A	acceptor_gain	0.9900
2:199959266:A:AC	acceptor_loss	0.9900
2:199959267:G:GG	acceptor_gain	0.9900
2:199959337:GAG:G	donor_gain	0.9900
2:199959337:GAGG:G	donor_loss	0.9900
2:199959341:T:A	donor_loss	0.9900
2:199959752:A:AG	acceptor_gain	0.9900
2:199959753:G:GG	acceptor_gain	0.9900
2:199959753:GGT:G	acceptor_gain	0.9900
2:199959876:GAAAG:G	donor_gain	0.9900
2:199962086:A:T	donor_gain	0.9900
2:199962090:T:G	donor_gain	0.9900

AlphaMissense

1881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:199963735:T:C	F267S	0.999
2:199963770:T:A	W279R	0.999
2:199963770:T:C	W279R	0.999
2:199956213:T:C	F139L	0.998
2:199956215:C:A	F139L	0.998
2:199956215:C:G	F139L	0.998
2:199956228:T:C	F144L	0.998
2:199956230:C:A	F144L	0.998
2:199956230:C:G	F144L	0.998
2:199963734:T:C	F267L	0.998
2:199963736:T:A	F267L	0.998
2:199963736:T:G	F267L	0.998
2:199963772:G:C	W279C	0.998
2:199963772:G:T	W279C	0.998
2:199956229:T:C	F144S	0.995
2:199959284:C:T	S156F	0.995
2:199961793:T:A	V221D	0.995
2:199961919:C:A	A263E	0.995
2:199963735:T:G	F267C	0.995
2:199956214:T:C	F139S	0.994
2:199956240:G:C	A148P	0.994
2:199961789:T:C	F220L	0.994
2:199961791:T:A	F220L	0.994
2:199961791:T:G	F220L	0.994
2:199963746:T:C	F271L	0.994
2:199963747:T:C	F271S	0.994
2:199963748:C:A	F271L	0.994
2:199963748:C:G	F271L	0.994
2:199963777:T:A	I281N	0.994
2:199959283:T:C	S156P	0.993

dbSNP variants (sampled 300 via entrez): RS1000237398 (2:199954769 G>A,C), RS1000264305 (2:199962165 C>G), RS1000400058 (2:199953802 T>C), RS1000437411 (2:199955066 G>T), RS1000698183 (2:199962578 ACT>A), RS1000771000 (2:199954091 C>T), RS1001677354 (2:199954608 A>AT), RS1002036555 (2:199958490 G>C,T), RS1002526158 (2:199963374 G>A), RS1003247104 (2:199959539 CATG>C), RS1003752504 (2:199963876 T>A,C), RS1003938770 (2:199954641 T>G), RS1004706813 (2:199959041 T>A), RS1004759312 (2:199958696 T>G), RS1004948494 (2:199959865 T>C)

Disease associations

OMIM: gene MIM:617267 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000323_5	Response to treatment for acute lymphoblastic leukemia	9.000000e-07
GCST002149_16	Schizophrenia	1.000000e-08
GCST004036_2	LDL cholesterol to HDL cholesterol ratio	9.000000e-09
GCST004521_125	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST005081_3	Bipolar disorder lithium response (continuous) or schizophrenia	4.000000e-08
GCST006803_6	Schizophrenia	4.000000e-17
GCST007561_69	Sleep duration	2.000000e-08
GCST009844_1	Creativity	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007930	LDL cholesterol:HDL cholesterol ratio
EFO:0010650	creativity measurement

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
Acetaminophen	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
cylindrospermopsin	increases expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
bisphenol S	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Atrazine	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	affects expression	1
Hydrogen Peroxide	affects expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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