APOOL

Summary

APOOL (apolipoprotein O like, HGNC:24009) is a protein-coding gene on chromosome Xq21.1, encoding MICOS complex subunit MIC27 (Q6UXV4). Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.

This gene encodes a protein which contains an apolipoprotein O superfamily domain. This domain is found on proteins in circulating lipoprotein complexes.

Source: NCBI Gene 139322 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 116 total — 14 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_198450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24009
Approved symbol	APOOL
Name	apolipoprotein O like
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	UNQ8193, AAIR8193, Mic27, MICOS27
Ensembl gene	ENSG00000155008
Ensembl biotype	protein_coding
OMIM	300955
Entrez	139322

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000373173, ENST00000895507, ENST00000895508

RefSeq mRNA: 1 — MANE Select: NM_198450 NM_198450

CCDS: CCDS48138

Canonical transcript exons

ENST00000373173 — 9 exons

Exon	Start	End
ENSE00001018759	85054344	85054398
ENSE00001018761	85051389	85051508
ENSE00001018762	85067127	85067218
ENSE00001190497	85073998	85074111
ENSE00001214782	85074274	85074391
ENSE00001294157	85055827	85055925
ENSE00001459714	85087590	85093315
ENSE00001459717	85003877	85003927
ENSE00001708477	85046446	85046550

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.0933 / max 107.3570, expressed in 1726 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196838	10.0933	1726

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.20	gold quality
biceps brachii	UBERON:0001507	94.52	gold quality
diaphragm	UBERON:0001103	93.72	gold quality
heart right ventricle	UBERON:0002080	93.13	gold quality
left ventricle myocardium	UBERON:0006566	92.68	gold quality
blood vessel layer	UBERON:0004797	91.54	gold quality
myocardium	UBERON:0002349	91.45	gold quality
skeletal muscle tissue	UBERON:0001134	90.41	gold quality
deltoid	UBERON:0001476	90.39	gold quality
vastus lateralis	UBERON:0001379	90.33	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.30	gold quality
quadriceps femoris	UBERON:0001377	90.00	gold quality
parietal pleura	UBERON:0002400	89.97	gold quality
hair follicle	UBERON:0002073	89.80	silver quality
muscle tissue	UBERON:0002385	89.41	gold quality
visceral pleura	UBERON:0002401	89.36	gold quality
pleura	UBERON:0000977	89.18	gold quality
endothelial cell	CL:0000115	88.91	silver quality
cardiac muscle of right atrium	UBERON:0003379	88.68	gold quality
tibialis anterior	UBERON:0001385	88.37	gold quality
pigmented layer of retina	UBERON:0001782	87.99	gold quality
buccal mucosa cell	CL:0002336	87.92	gold quality
tibia	UBERON:0000979	87.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.03	gold quality
nephron tubule	UBERON:0001231	86.39	gold quality
upper leg skin	UBERON:0004262	86.21	gold quality
CA1 field of hippocampus	UBERON:0003881	86.19	gold quality
colonic mucosa	UBERON:0000317	86.09	gold quality
esophagus squamous epithelium	UBERON:0006920	86.07	gold quality
cauda epididymis	UBERON:0004360	86.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	647.06
E-ANND-3	yes	7.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

249 targeting APOOL, 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-3924	100.00	72.09	2394
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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-568	99.98	69.86	2084
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

Literature-anchored findings (GeneRIF, showing 2)

• APOOL is a cardiolipin-binding component of the Mitofilin/MINOS protein complex. (PMID:23704930)
• MIC26 and MIC27 cooperate to regulate cardiolipin levels and the landscape of OXPHOS complexes. (PMID:32788226)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	apool	ENSDARG00000039374
mus_musculus	Apool	ENSMUSG00000025525
rattus_norvegicus	Apool	ENSRNOG00000082020
drosophila_melanogaster	Mic26-27	FBGN0038400
caenorhabditis_elegans		WBGENE00019333

Paralogs (1): APOO (ENSG00000184831)

Protein

Protein identifiers

MICOS complex subunit MIC27 — Q6UXV4 (reviewed: Q6UXV4)

Alternative names: Apolipoprotein O-like, Protein FAM121A

All UniProt accessions (1): Q6UXV4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Specifically binds to cardiolipin (in vitro) but not to the precursor lipid phosphatidylglycerol. Plays a crucial role in crista junction formation and mitochondrial function,.

Subunit / interactions. Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with MICOS10/MIC10, IMMT/MIC60 and APOO/MIC23/MIC26.

Subcellular location. Mitochondrion inner membrane. Mitochondrion.

Similarity. Belongs to the apolipoprotein O/MICOS complex subunit Mic27 family.

RefSeq proteins (1): NP_940852* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019166	MIC26/MIC27	Family
IPR033182	MIC26/MIC27_animal	Family

Pfam: PF09769

UniProt features (11 total): topological domain 3, transmembrane region 2, compositionally biased region 2, transit peptide 1, chain 1, modified residue 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXV4-F1	70.83	0.30

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 (1): 204

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-8949613	Cristae formation
R-HSA-109582	Hemostasis
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 171 (showing top): GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CRISTAE_FORMATION, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOCC_MITOCHONDRIAL_ENVELOPE, BASAKI_YBX1_TARGETS_DN, GOBP_MEMBRANE_ORGANIZATION, GATA1_02, ISRE_01, GATA_Q6, EVI1_04, SENESE_HDAC3_TARGETS_DN, GOCC_PLATELET_ALPHA_GRANULE, GOCC_SECRETORY_VESICLE

GO Biological Process (2): inner mitochondrial membrane organization (GO:0007007), cristae formation (GO:0042407)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): SAM complex (GO:0001401), extracellular region (GO:0005576), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), platelet alpha granule lumen (GO:0031093), mitochondrial crista junction (GO:0044284), MICOS complex (GO:0061617), MIB complex (GO:0140275), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Mitochondrial biogenesis	1
Organelle biogenesis and maintenance	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
inner mitochondrial membrane protein complex	2
mitochondrial membrane organization	1
inner mitochondrial membrane organization	1
binding	1
mitochondrial outer membrane translocase complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
platelet alpha granule	1
secretory granule lumen	1
mitochondrial inner membrane	1
organelle membrane contact site	1

Protein interactions and networks

STRING

1066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOOL	CHCHD6	Q9BRQ6	993
APOOL	CHCHD3	Q9NX63	993
APOOL	MICOS13	Q5XKP0	991
APOOL	IMMT	Q16891	985
APOOL	APOO	Q9BUR5	984
APOOL	MICOS10	Q5TGZ0	965
APOOL	CHCHD5	Q9BSY4	805
APOOL	DNAJC11	Q9NVH1	792
APOOL	SAMM50	Q9Y512	726
APOOL	MTX2	O75431	684
APOOL	CHCHD10	Q8WYQ3	654
APOOL	SATL1	Q86VE3	613
APOOL	MTX1	Q13505	596
APOOL	ARMC1	Q9NVT9	582
APOOL	ZNF711	Q9Y462	569

IntAct

63 interactions, top by confidence:

A	B	Type	Score
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
AIFM1	AK2	psi-mi:“MI:0914”(association)	0.570
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
APOOL	BNRF1	psi-mi:“MI:0915”(physical association)	0.370
NDUFA12	NDUFS8	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
SLC1A1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
AIFM1	NR2F2	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
MICOS13	MTX2	psi-mi:“MI:0914”(association)	0.350
APOOL	MGST3	psi-mi:“MI:0914”(association)	0.350
APOOL	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
NMES1	COX7A2L	psi-mi:“MI:0914”(association)	0.350
NMES1	TIMM44	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (112): APOOL (Affinity Capture-MS), APOOL (Affinity Capture-MS), DNAJC11 (Affinity Capture-MS), APOOL (Affinity Capture-MS), APOOL (Affinity Capture-MS), MTX2 (Affinity Capture-MS), CHCHD6 (Affinity Capture-MS), APOOL (Affinity Capture-MS), RMDN3 (Affinity Capture-MS), CHCHD3 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), STARD7 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), MTX1 (Affinity Capture-MS), IMMT (Affinity Capture-MS)

ESM2 similar proteins: A0A1A6FVD4, A0JNJ3, A1XQR7, A4IJ20, A7MBC7, B9X187, G3HPD1, O48832, O82803, P02655, P0DN40, P12278, P19034, P43883, Q08D83, Q148H0, Q1MTD4, Q21154, Q2ACH7, Q3SZ27, Q41112, Q4PLW0, Q4V8S3, Q5CZQ0, Q5NVS6, Q5R987, Q5XIJ4, Q5XKP0, Q5ZK55, Q5ZML6, Q63ZZ0, Q6DFJ3, Q6DH88, Q6UXV4, Q6ZQE4, Q78IK4, Q7YRC0, Q8BGY7, Q8MJN0, Q8N0X7

Diamond homologs: Q148H0, Q3SZ27, Q5NVS6, Q5ZK55, Q6UXV4, Q78IK4, Q9BUR5, Q9DCZ4, Q21154

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	1
Uncertain significance	36
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
146002	GRCh38/hg38 Xq21.1-21.2(chrX:81930916-85965282)x1	Pathogenic
150837	GRCh38/hg38 Xq21.1-21.31(chrX:80722314-92152619)x0	Pathogenic
1526822	GRCh37/hg19 Xq21.1-21.2(chrX:78104966-86189374)	Pathogenic
4683020	GRCh37/hg19 Xq21.1-22.3(chrX:77574432-106660031)x1	Pathogenic
57134	GRCh38/hg38 Xq21.1-21.31(chrX:79372269-91308122)x1	Pathogenic
57928	GRCh38/hg38 Xq21.1-21.2(chrX:80329330-86150446)x1	Pathogenic
57931	GRCh38/hg38 Xq21.1-21.2(chrX:81762601-86471468)x1	Pathogenic
57965	GRCh38/hg38 Xq21.1-21.2(chrX:81762602-86457999)x1	Pathogenic
57967	GRCh38/hg38 Xq21.1-21.2(chrX:81765008-86444979)x0	Pathogenic
686630	GRCh37/hg19 Xq13.3-21.31(chrX:74667077-90312981)x1	Pathogenic
831865	NC_000023.10:g.(?83126460)(86924394_?)del	Pathogenic
832734	NC_000023.10:g.(?83576897)(86924394_?)del	Pathogenic
833457	NC_000023.10:g.(?82763333)(86924394_?)del	Pathogenic
833482	NC_000023.10:g.(?83372068)(86924394_?)del	Pathogenic
1807759	GRCh37/hg19 Xq21.1-21.2(chrX:84343474-84990478)x0	Likely pathogenic

SpliceAI

1705 predictions. Top by Δscore:

Variant	Effect	Δscore
X:85003926:GG:G	donor_gain	1.0000
X:85003927:GG:G	donor_gain	1.0000
X:85055815:T:A	acceptor_gain	1.0000
X:85087577:A:AG	acceptor_gain	1.0000
X:85092558:CTAT:C	acceptor_gain	1.0000
X:85092559:TAT:T	acceptor_gain	1.0000
X:85092562:C:CC	acceptor_gain	1.0000
X:85092563:T:A	acceptor_loss	1.0000
X:85003927:GGTAA:G	donor_loss	0.9900
X:85003928:G:GG	donor_gain	0.9900
X:85003929:T:G	donor_loss	0.9900
X:85046440:TCTTA:T	acceptor_loss	0.9900
X:85046441:CTTA:C	acceptor_loss	0.9900
X:85046442:TTAGA:T	acceptor_loss	0.9900
X:85046443:TA:T	acceptor_loss	0.9900
X:85046444:A:AG	acceptor_gain	0.9900
X:85046444:AG:A	acceptor_loss	0.9900
X:85046444:AGAT:A	acceptor_gain	0.9900
X:85046444:AGATG:A	acceptor_gain	0.9900
X:85046445:G:GG	acceptor_gain	0.9900
X:85046445:GAT:G	acceptor_gain	0.9900
X:85046445:GATG:G	acceptor_gain	0.9900
X:85046445:GATGG:G	acceptor_gain	0.9900
X:85051384:TGTA:T	acceptor_loss	0.9900
X:85051385:GTA:G	acceptor_loss	0.9900
X:85051386:TA:T	acceptor_loss	0.9900
X:85051387:A:AG	acceptor_gain	0.9900
X:85051387:AGCT:A	acceptor_loss	0.9900
X:85051388:G:GA	acceptor_gain	0.9900
X:85051505:CAAGG:C	donor_loss	0.9900

AlphaMissense

1726 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:85067184:T:A	V151D	0.969
X:85055890:T:A	V120D	0.946
X:85087664:A:C	S265R	0.933
X:85087666:C:A	S265R	0.933
X:85087666:C:G	S265R	0.933
X:85067186:T:C	C152R	0.931
X:85067174:G:A	G148R	0.927
X:85067174:G:C	G148R	0.927
X:85055887:C:A	T119K	0.920
X:85067166:C:A	A145D	0.920
X:85087673:A:C	S268R	0.919
X:85087675:C:A	S268R	0.919
X:85087675:C:G	S268R	0.919
X:85087672:A:C	R267S	0.914
X:85087672:A:T	R267S	0.914
X:85055905:G:A	G125D	0.909
X:85067214:C:A	A161D	0.909
X:85067159:G:A	G143R	0.908
X:85067159:G:C	G143R	0.908
X:85087649:G:C	D260H	0.908
X:85055884:T:A	I118N	0.903
X:85067160:G:A	G143E	0.894
X:85055842:T:C	L104P	0.892
X:85055862:T:C	F111L	0.889
X:85055864:T:A	F111L	0.889
X:85055864:T:G	F111L	0.889
X:85055884:T:G	I118S	0.888
X:85067177:G:C	A149P	0.887
X:85067175:G:A	G148E	0.886
X:85051474:G:C	R69P	0.885

dbSNP variants (sampled 300 via entrez): RS1000003272 (X:85057473 T>C), RS1000022622 (X:85074457 A>C), RS1000076861 (X:85022380 C>T), RS1000116122 (X:85048085 G>A,C), RS1000125313 (X:85067558 G>A), RS1000166875 (X:85057463 CATATAT>C,CATAT,CATATATAT), RS1000294292 (X:85004279 G>A), RS1000320605 (X:85038530 T>G), RS1000362410 (X:85046693 G>A), RS1000461674 (X:85057816 A>T), RS1000537215 (X:85092070 A>G), RS1000541220 (X:85023023 T>C,G), RS1000562225 (X:85013986 T>A), RS1000573458 (X:85014389 T>C), RS1000643038 (X:85029497 G>A,C,T)

Disease associations

OMIM: gene MIM:300955 | 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

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression, increases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Formaldehyde	decreases expression	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Isotretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SD01	HAP1 APOOL (-) 1	Cancer cell line	Male
CVCL_SD02	HAP1 APOOL (-) 2	Cancer cell line	Male
CVCL_SD03	HAP1 APOOL (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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