ATPAF1

Summary

ATPAF1 (ATP synthase mitochondrial F1 complex assembly factor 1, HGNC:18803) is a protein-coding gene on chromosome 1p33, encoding ATP synthase mitochondrial F1 complex assembly factor 1 (Q5TC12). Has a complex stabilizing activity in the assembly of the mitochondrial F1-F0 complex.

This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 beta subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. Alternatively spliced transcript variants have been identified.

Source: NCBI Gene 64756 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_001394565

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18803
Approved symbol	ATPAF1
Name	ATP synthase mitochondrial F1 complex assembly factor 1
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22351, Atp11p, ATP11
Ensembl gene	ENSG00000123472
Ensembl biotype	protein_coding
OMIM	608917
Entrez	64756

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000329231, ENST00000460928, ENST00000474020, ENST00000487193, ENST00000492233, ENST00000525633, ENST00000526821, ENST00000529214, ENST00000532925, ENST00000534216, ENST00000574428, ENST00000576409, ENST00000870202, ENST00000870203, ENST00000870204, ENST00000870205, ENST00000870206, ENST00000870207, ENST00000870208, ENST00000870209, ENST00000870210, ENST00000923240, ENST00000923241

RefSeq mRNA: 5 — MANE Select: NM_001394565 NM_001042546, NM_001243728, NM_001256418, NM_001394565, NM_022745

CCDS: CCDS41327, CCDS541, CCDS57998, CCDS90944

Canonical transcript exons

ENST00000574428 — 9 exons

Exon	Start	End
ENSE00002674976	46632737	46635970
ENSE00003496170	46658127	46658189
ENSE00003561469	46658687	46658737
ENSE00003568617	46653817	46653867
ENSE00003599785	46645161	46645256
ENSE00003636921	46665256	46665364
ENSE00003649150	46652581	46652628
ENSE00003661657	46643194	46643301
ENSE00003751279	46668057	46668364

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.5975 / max 103.7622, expressed in 1760 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12191	10.5132	1738
12194	0.8969	605
12192	0.6347	326
12193	0.3989	172
12195	0.1477	43
12190	0.0061	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.14	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.55	gold quality
myocardium	UBERON:0002349	98.12	gold quality
heart left ventricle	UBERON:0002084	97.81	gold quality
cardiac ventricle	UBERON:0002082	97.79	gold quality
vastus lateralis	UBERON:0001379	97.69	gold quality
right adrenal gland cortex	UBERON:0035827	97.62	gold quality
quadriceps femoris	UBERON:0001377	97.60	gold quality
right adrenal gland	UBERON:0001233	97.56	gold quality
heart right ventricle	UBERON:0002080	97.54	gold quality
apex of heart	UBERON:0002098	97.46	gold quality
cardiac atrium	UBERON:0002081	97.45	gold quality
right atrium auricular region	UBERON:0006631	97.41	gold quality
gastrocnemius	UBERON:0001388	97.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.33	gold quality
caudate nucleus	UBERON:0001873	97.25	gold quality
muscle of leg	UBERON:0001383	97.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.22	gold quality
sperm	CL:0000019	97.21	gold quality
heart	UBERON:0000948	97.19	gold quality
prefrontal cortex	UBERON:0000451	97.13	gold quality
nucleus accumbens	UBERON:0001882	97.09	gold quality
putamen	UBERON:0001874	97.08	gold quality
left adrenal gland	UBERON:0001234	97.02	gold quality
deltoid	UBERON:0001476	96.96	gold quality
left adrenal gland cortex	UBERON:0035825	96.88	gold quality
skeletal muscle tissue	UBERON:0001134	96.86	gold quality
adrenal cortex	UBERON:0001235	96.86	gold quality
anterior cingulate cortex	UBERON:0009835	96.79	gold quality
amygdala	UBERON:0001876	96.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.86
E-MTAB-6386	no	209.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting ATPAF1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-767-3P	98.61	67.69	1192

Literature-anchored findings (GeneRIF, showing 1)

• Asthma was found to be associated with a cluster of SNPs and SNP haplotypes containing the ATPAF1 gene (PMID:21696813)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atpaf1	ENSDARG00000042799
mus_musculus	Atpaf1	ENSMUSG00000028710
rattus_norvegicus	Atpaf1	ENSRNOG00000010169
drosophila_melanogaster	CG10340	FBGN0022344

Protein

Protein identifiers

ATP synthase mitochondrial F1 complex assembly factor 1 — Q5TC12 (reviewed: Q5TC12)

Alternative names: ATP11 homolog

All UniProt accessions (8): A8MRA7, Q5TC12, E9PPX6, H0YCA6, H0YD21, H0YDD6, H0YEW4, I3L448

UniProt curated annotations — full annotation on UniProt →

Function. Has a complex stabilizing activity in the assembly of the mitochondrial F1-F0 complex.

Subunit / interactions. Interacts with ATP5F1B; involved in the assembly of the F1 component of the mitochondrial ATP synthase (ATPase).

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Weakly expressed in muscle.

Similarity. Belongs to the ATP11 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5TC12-1	1	yes
Q5TC12-2	2
Q5TC12-3	3

RefSeq proteins (5): NP_001036011, NP_001230657, NP_001243347, NP_001381494, NP_073582 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010591	ATP11	Family

Pfam: PF06644

UniProt features (5 total): splice variant 2, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TC12-F1	76.31	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): LU_IL4_SIGNALING, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOCC_MITOCHONDRIAL_ENVELOPE, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, SENESE_HDAC3_TARGETS_DN, NUYTTEN_EZH2_TARGETS_DN, GOCC_ORGANELLE_INNER_MEMBRANE, NUYTTEN_NIPP1_TARGETS_DN, GOCC_ORGANELLE_ENVELOPE, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, GOBP_PROTON_TRANSPORTING_TWO_SECTOR_ATPASE_COMPLEX_ASSEMBLY, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, NFE2L2.V2, KAT2A_TARGET_GENES

GO Biological Process (2): mitochondrial proton-transporting ATP synthase complex assembly (GO:0033615), protein-containing complex assembly (GO:0065003)

GO Molecular Function (2): protein-containing complex stabilizing activity (GO:0140777), protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	1
mitochondrial respiratory chain complex assembly	1
proton-transporting ATP synthase complex assembly	1
cellular component assembly	1
protein-containing complex organization	1
molecular_function	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATPAF1	ATP5F1A	P25705	980
ATPAF1	ATPAF2	Q8N5M1	980
ATPAF1	ATP5F1B	P06576	969
ATPAF1	ATP5F1C	P36542	867
ATPAF1	TMEM70	Q9BUB7	769
ATPAF1	MT-ATP8	P03928	652
ATPAF1	MT-ATP6	P00846	624
ATPAF1	ATP23	Q9Y6H3	615
ATPAF1	ATP6V1E2	Q96A05	538
ATPAF1	ATP5PB	P24539	502
ATPAF1	ARMCX2	Q7L311	475
ATPAF1	BCS1L	Q9Y276	471
ATPAF1	COX11	Q9Y6N1	470
ATPAF1	TEX38	Q6PEX7	442
ATPAF1	BCAS4	Q8TDM0	441

IntAct

51 interactions, top by confidence:

A	B	Type	Score
ATPAF1	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.740
ATP5F1B	ATP5PD	psi-mi:“MI:0914”(association)	0.670
MRRF	DBT	psi-mi:“MI:0914”(association)	0.620
OTC	RTL8C	psi-mi:“MI:0914”(association)	0.530
ERAL1	COL1A1	psi-mi:“MI:0914”(association)	0.530
OXCT2	HSPD1	psi-mi:“MI:0914”(association)	0.530
ATP5F1B	SCAMP2	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
ATPAF1	ATP2	psi-mi:“MI:0915”(physical association)	0.370
RAD18	SRGAP3	psi-mi:“MI:0914”(association)	0.350
YBEY	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFS7		psi-mi:“MI:0914”(association)	0.350
ATP5F1B	ATP5PD	psi-mi:“MI:0914”(association)	0.350
RPUSD3	ANXA1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MRM2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
KDF1	MLYCD	psi-mi:“MI:0914”(association)	0.350
ATPAF1	TOP3A	psi-mi:“MI:0914”(association)	0.350
MRM2	VWA8	psi-mi:“MI:0914”(association)	0.350
YARS2	VWA8	psi-mi:“MI:0914”(association)	0.350
ACSM5	VWA8	psi-mi:“MI:0914”(association)	0.350
FAHD1	VWA8	psi-mi:“MI:0914”(association)	0.350
ERAL1	POLRMT	psi-mi:“MI:0914”(association)	0.350
MTG2	BCKDK	psi-mi:“MI:0914”(association)	0.350
DHRS2	CPS1	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
SLC22A2	RAB27B	psi-mi:“MI:0914”(association)	0.350
SULF2	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), ATPAF1 (Proximity Label-MS), ATPAF1 (Proximity Label-MS), ATPAF1 (Proximity Label-MS), ATPAF1 (Proximity Label-MS), ATPAF1 (Proximity Label-MS), ATPAF1 (Proximity Label-MS)

ESM2 similar proteins: A0A8I6ASZ5, A0JN53, A4IG66, D3Z8X7, D3ZND0, G3X992, O00750, O08836, O70576, P0DKR2, Q15021, Q1JQC5, Q1L5Z9, Q1LWH4, Q1LXZ7, Q2YD98, Q3T1I9, Q3TV65, Q3UJU9, Q4R5Q4, Q5EAU9, Q5JTW2, Q5R6Z1, Q5TC12, Q61249, Q66H15, Q6NY52, Q6P5E6, Q6PBQ2, Q6PI26, Q80TE0, Q80V31, Q80XC6, Q8BIW9, Q8BM55, Q8K2Z4, Q8R3L2, Q8VDP4, Q8WVB6, Q92574

Diamond homologs: P32453, P87127, Q1L987, Q5TC12, Q66JD1, Q811I0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 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
Mitochondrial protein degradation	8	20.8×	8e-07
Mitochondrial protein import	5	19.1×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1934 predictions. Top by Δscore:

Variant	Effect	Δscore
1:46635967:CATT:C	acceptor_gain	1.0000
1:46635969:TT:T	acceptor_gain	1.0000
1:46652579:A:AC	donor_gain	1.0000
1:46652580:C:CC	donor_gain	1.0000
1:46658191:T:C	acceptor_gain	1.0000
1:46658191:T:TC	acceptor_gain	1.0000
1:46658734:CTGT:C	acceptor_gain	1.0000
1:46658738:C:CC	acceptor_gain	1.0000
1:46668052:CGCA:C	donor_loss	1.0000
1:46668053:GCAC:G	donor_loss	1.0000
1:46668054:CA:C	donor_loss	1.0000
1:46668056:C:CT	donor_loss	1.0000
1:46671972:G:GG	donor_gain	1.0000
1:46635968:ATTCT:A	acceptor_loss	0.9900
1:46635970:TC:T	acceptor_loss	0.9900
1:46635971:C:CC	acceptor_gain	0.9900
1:46635971:CTGT:C	acceptor_loss	0.9900
1:46635972:T:A	acceptor_loss	0.9900
1:46652561:CGTGA:C	donor_gain	0.9900
1:46653815:A:AC	donor_gain	0.9900
1:46653816:C:CC	donor_gain	0.9900
1:46658190:C:CC	acceptor_gain	0.9900
1:46658681:ACCT:A	donor_loss	0.9900
1:46658682:CCTA:C	donor_loss	0.9900
1:46658683:CTA:C	donor_loss	0.9900
1:46658684:TA:T	donor_loss	0.9900
1:46658735:TGT:T	acceptor_gain	0.9900
1:46658736:GT:G	acceptor_gain	0.9900
1:46658738:CTGA:C	acceptor_loss	0.9900
1:46658739:T:C	acceptor_loss	0.9900

AlphaMissense

2130 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:46643273:A:G	L238P	0.997
1:46635860:G:C	F301L	0.996
1:46635860:G:T	F301L	0.996
1:46635862:A:G	F301L	0.996
1:46653864:A:G	W165R	0.996
1:46653864:A:T	W165R	0.996
1:46635846:A:T	V306D	0.995
1:46635958:C:G	A269P	0.995
1:46645189:A:G	L219P	0.995
1:46645254:A:C	F197L	0.995
1:46645254:A:T	F197L	0.995
1:46645256:A:G	F197L	0.995
1:46635861:A:G	F301S	0.994
1:46645205:A:G	W214R	0.994
1:46645205:A:T	W214R	0.994
1:46635945:G:T	A273D	0.993
1:46643217:C:G	A257P	0.993
1:46652600:C:G	R190P	0.993
1:46668072:A:G	I84T	0.993
1:46635926:G:C	F279L	0.992
1:46635926:G:T	F279L	0.992
1:46635928:A:G	F279L	0.992
1:46653828:C:G	A177P	0.991
1:46645246:G:T	A200D	0.990
1:46645255:A:G	F197S	0.990
1:46635946:C:G	A273P	0.989
1:46645243:A:G	L201P	0.989
1:46653862:C:A	W165C	0.989
1:46653862:C:G	W165C	0.989
1:46643225:A:T	L254Q	0.988

dbSNP variants (sampled 300 via entrez): RS1000007667 (1:46665775 A>C,G), RS1000123089 (1:46666098 G>A), RS1000131378 (1:46637355 G>A,C), RS1000334676 (1:46669985 G>C), RS1000422655 (1:46663130 G>A), RS1000972246 (1:46652065 A>G), RS1001019900 (1:46651045 A>G,T), RS1001123992 (1:46657210 T>C), RS1001136725 (1:46635808 G>A,C), RS1001302187 (1:46652457 C>A), RS1001497588 (1:46643730 A>G), RS1001569004 (1:46667031 C>T), RS1001580934 (1:46637433 T>A), RS1001612050 (1:46645447 G>A,C), RS1001629567 (1:46663777 AC>A)

Disease associations

OMIM: gene MIM:608917 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Ozone	decreases expression, increases abundance, affects cotreatment	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects expression	1
ochratoxin A	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Catechin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Folic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SE23	HAP1 ATPAF1 (-) 1	Cancer cell line	Male
CVCL_SE24	HAP1 ATPAF1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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