AP5M1

Summary

AP5M1 (adaptor related protein complex 5 subunit mu 1, HGNC:20192) is a protein-coding gene on chromosome 14q22.3, encoding AP-5 complex subunit mu-1 (Q9H0R1). As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport.

Involved in endosomal transport. Located in several cellular components, including cytosol; late endosome; and lysosome. Part of AP-type membrane coat adaptor complex.

Source: NCBI Gene 55745 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 78 total — 3 likely-pathogenic
• MANE Select transcript: NM_018229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20192
Approved symbol	AP5M1
Name	adaptor related protein complex 5 subunit mu 1
Location	14q22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10813, MuD, mu5
Ensembl gene	ENSG00000053770
Ensembl biotype	protein_coding
OMIM	614368
Entrez	55745

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000261558, ENST00000431972, ENST00000554213, ENST00000554863, ENST00000554931, ENST00000555448, ENST00000556377, ENST00000556723, ENST00000556995, ENST00000854558, ENST00000854559, ENST00000921974

RefSeq mRNA: 1 — MANE Select: NM_018229 NM_018229

CCDS: CCDS9729

Canonical transcript exons

ENST00000261558 — 8 exons

Exon	Start	End
ENSE00001094511	57286223	57286319
ENSE00001094514	57274244	57274889
ENSE00001908374	57288802	57298742
ENSE00001924315	57268971	57269388
ENSE00003475724	57280195	57280422
ENSE00003557748	57283112	57283230
ENSE00003660326	57282089	57282228
ENSE00003679438	57282934	57283019

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.9343 / max 1089.8363, expressed in 1798 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139806	14.6267	1748
139804	2.2981	978
139798	1.6824	698
139800	1.5735	989
139801	0.9254	583
139803	0.7691	418
139802	0.3997	181
139805	0.3098	93
139807	0.2109	106
139799	0.1315	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	97.57	gold quality
choroid plexus epithelium	UBERON:0003911	97.03	gold quality
endothelial cell	CL:0000115	96.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.39	gold quality
colonic mucosa	UBERON:0000317	96.19	gold quality
jejunum	UBERON:0002115	94.79	gold quality
pigmented layer of retina	UBERON:0001782	94.75	gold quality
retina	UBERON:0000966	94.73	gold quality
eye	UBERON:0000970	94.54	gold quality
palpebral conjunctiva	UBERON:0001812	94.48	gold quality
rectum	UBERON:0001052	94.40	gold quality
heart right ventricle	UBERON:0002080	94.37	gold quality
duodenum	UBERON:0002114	94.09	gold quality
esophagus squamous epithelium	UBERON:0006920	94.02	gold quality
nephron tubule	UBERON:0001231	93.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.34	gold quality
biceps brachii	UBERON:0001507	93.33	gold quality
corpus epididymis	UBERON:0004359	93.00	gold quality
oral cavity	UBERON:0000167	92.96	gold quality
epithelium of nasopharynx	UBERON:0001951	92.91	gold quality
caput epididymis	UBERON:0004358	92.91	gold quality
nasopharynx	UBERON:0001728	92.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.74	gold quality
substantia nigra pars compacta	UBERON:0001965	92.69	gold quality
middle temporal gyrus	UBERON:0002771	92.60	gold quality
epithelium of esophagus	UBERON:0001976	92.57	gold quality
squamous epithelium	UBERON:0006914	92.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.46	gold quality
parietal pleura	UBERON:0002400	92.40	gold quality
ileal mucosa	UBERON:0000331	92.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting AP5M1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-1273H-3P	99.29	67.55	980

Literature-anchored findings (GeneRIF, showing 4)

• The gene encoding the protein MUDENG (Mu-2 related death-inducing gene) was cloned and characterized. (PMID:18395520)
• These results suggest that the adaptin domain plays a key role in MUDENG-mediated cell death. (PMID:23665015)
• The AP5M1 upregulated the level of BAX protein, a key pro-apoptotic B cell lymphoma (BCL)-2 family member regulating mitochondrial apoptotic cell death pathway. (PMID:31427081)
• The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy? (PMID:32759789)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ap5m1	ENSDARG00000031533
mus_musculus	Ap5m1	ENSMUSG00000036291
rattus_norvegicus	Ap5m1	ENSRNOG00000014148

Protein

Protein identifiers

AP-5 complex subunit mu-1 — Q9H0R1 (reviewed: Q9H0R1)

Alternative names: Adaptor-related protein complex 5 subunit mu-1, Mu-2-related death-inducing protein, Putative HIV-1 infection-related protein

All UniProt accessions (6): E7EQ45, Q9H0R1, G3V3L4, G3V573, H0YIY0, S4R311

UniProt curated annotations — full annotation on UniProt →

Function. As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport. According to PubMed:18395520, it may play a role in cell death.

Subunit / interactions. Probably part of the adaptor protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1.

Subcellular location. Cytoplasm. Cytosol. Late endosome membrane. Lysosome membrane.

Tissue specificity. Expressed in various tumor cell lines including Jurkat, Hep-G2 and HeLa.

Miscellaneous. May be due to an intron retention.

Similarity. Belongs to the adaptor complexes medium subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0R1-1	1	yes
Q9H0R1-2	2

RefSeq proteins (1): NP_060699* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028565	MHD	Domain
IPR036168	AP2_Mu_C_sf	Homologous_superfamily
IPR039591	AP5M1	Family

Pfam: PF00928

UniProt features (7 total): splice variant 2, sequence variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0R1-F1	87.31	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): MYOGENIN_Q6, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, CATRRAGC_UNKNOWN, OCT1_03, TIEN_INTESTINE_PROBIOTICS_24HR_UP, NRF2_01, GOBP_LYTIC_VACUOLE_ORGANIZATION, CUI_TCF21_TARGETS_2_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS

GO Biological Process (3): protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), endosomal transport (GO:0016197)

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

GO Cellular Component (11): lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), cytosol (GO:0005829), membrane (GO:0016020), AP-type membrane coat adaptor complex (GO:0030119), late endosome membrane (GO:0031902), AP-5 adaptor complex (GO:0044599), cytoplasm (GO:0005737), endosome (GO:0005768), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transport	2
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
vesicle-mediated transport	1
intracellular transport	1
binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endosome	1
cytoplasm	1
membrane coat	1
membrane protein complex	1
late endosome	1
endosome membrane	1
AP-type membrane coat adaptor complex	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP5M1	AP5S1	Q9NUS5	980
AP5M1	AP4M1	O00189	943
AP5M1	GSTM1	P09488	915
AP5M1	GSTM5	P46439	887
AP5M1	AP5B1	Q2VPB7	850
AP5M1	GSTM4	Q03013	759
AP5M1	AP5Z1	O43299	742
AP5M1	GSTM2	P28161	693
AP5M1	SPP1	P10451	582
AP5M1	SPG11	Q96JI7	554
AP5M1	SPINT2	O43291	548
AP5M1	FOXP1	Q9H334	544
AP5M1	LHX4	Q969G2	542
AP5M1	KMT2C	Q8NEZ4	500
AP5M1	A0A3B3IT14	A0A3B3IT14	490
AP5M1	PAXIP1	Q6ZW49	490

IntAct

17 interactions, top by confidence:

A	B	Type	Score
AP5S1	AP5B1	psi-mi:“MI:0914”(association)	0.800
SPG11	AP5Z1	psi-mi:“MI:0914”(association)	0.620
ZFYVE26	AP5Z1	psi-mi:“MI:0914”(association)	0.540
ZFYVE26	AP5Z1	psi-mi:“MI:0915”(physical association)	0.540
AP5S1	AP5Z1	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
Cep55	UMAD1	psi-mi:“MI:0914”(association)	0.350
PAX6	EPB41L2	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
AP5S1	NHERF1	psi-mi:“MI:0914”(association)	0.350
AP5M1	AP5B1	psi-mi:“MI:0914”(association)	0.350
AP5M1	HSPA12A	psi-mi:“MI:0914”(association)	0.350
MGARP	ZZEF1	psi-mi:“MI:0914”(association)	0.350
AP5Z1	AP5B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): DCAF4 (Affinity Capture-MS), GTF3C3 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), AP5B1 (Affinity Capture-MS), AP5M1 (Affinity Capture-MS), AP5M1 (Affinity Capture-MS), AP5B1 (Affinity Capture-MS), DCAF4 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), AP5B1 (Affinity Capture-MS), AP5M1 (Affinity Capture-MS), DCAF4 (Affinity Capture-MS), AP5M1 (Affinity Capture-MS), CKMT2 (Affinity Capture-MS)

ESM2 similar proteins: A4IH75, B0S6R1, F4K265, O14417, O75165, O94915, P28660, P60670, P97878, Q10LJ0, Q2HJE0, Q2TBN7, Q3B736, Q3B8G8, Q3TPX4, Q499N2, Q4R6Q7, Q4R708, Q556Y9, Q5E9X5, Q5R6U8, Q5R8B7, Q5RBT3, Q5VZE5, Q5XHA1, Q5ZHV2, Q642Q3, Q6AY69, Q6DE58, Q6DKG0, Q6GLR7, Q6NPF4, Q6P2C8, Q6PFL0, Q6PHQ8, Q6Q7J5, Q7T322, Q8BJ63, Q8TAT6, Q8VDP2

Diamond homologs: Q499N2, Q4R6Q7, Q5E9X5, Q8BJ63, Q9H0R1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AP5M1	“form complex”	“AP-5 Adaptor complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	64
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3777714	NM_018229.4(AP5M1):c.97C>T (p.Arg33Ter)	Likely pathogenic
3777715	NM_018229.4(AP5M1):c.1166G>A (p.Trp389Ter)	Likely pathogenic
394770	GRCh37/hg19 14q22.3(chr14:56559797-58063452)x1	Likely pathogenic

SpliceAI

1556 predictions. Top by Δscore:

Variant	Effect	Δscore
14:57269025:G:GT	donor_gain	1.0000
14:57269041:G:GT	donor_gain	1.0000
14:57274237:A:AG	acceptor_gain	1.0000
14:57274242:A:AG	acceptor_gain	1.0000
14:57274242:AGAC:A	acceptor_gain	1.0000
14:57274243:G:GG	acceptor_gain	1.0000
14:57274243:GAC:G	acceptor_gain	1.0000
14:57274243:GACG:G	acceptor_gain	1.0000
14:57274435:G:GT	donor_gain	1.0000
14:57280323:T:TA	donor_gain	1.0000
14:57280324:A:AA	donor_gain	1.0000
14:57281634:T:G	acceptor_gain	1.0000
14:57282930:A:AG	acceptor_gain	1.0000
14:57282931:A:G	acceptor_gain	1.0000
14:57282932:A:G	acceptor_gain	1.0000
14:57282933:G:GA	acceptor_gain	1.0000
14:57282933:GA:G	acceptor_gain	1.0000
14:57282933:GAGGT:G	acceptor_gain	1.0000
14:57283018:TGGT:T	donor_loss	1.0000
14:57283020:GTG:G	donor_loss	1.0000
14:57283021:T:G	donor_loss	1.0000
14:57283099:A:AG	acceptor_gain	1.0000
14:57283104:T:TA	acceptor_gain	1.0000
14:57283110:A:AG	acceptor_gain	1.0000
14:57283110:A:AT	acceptor_loss	1.0000
14:57283110:AG:A	acceptor_gain	1.0000
14:57283111:G:GA	acceptor_gain	1.0000
14:57283111:GG:G	acceptor_gain	1.0000
14:57283111:GGCC:G	acceptor_gain	1.0000
14:57283111:GGCCA:G	acceptor_gain	1.0000

AlphaMissense

3205 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:57274761:T:A	W198R	0.997
14:57274761:T:C	W198R	0.997
14:57283010:T:A	W389R	0.997
14:57283010:T:C	W389R	0.997
14:57288834:T:A	W475R	0.997
14:57288834:T:C	W475R	0.997
14:57274872:G:A	G235R	0.996
14:57274872:G:C	G235R	0.996
14:57274873:G:A	G235E	0.996
14:57282102:C:G	P321R	0.996
14:57282105:T:A	I322N	0.996
14:57282200:T:C	C354R	0.996
14:57286281:T:A	V451D	0.996
14:57274879:T:A	V237E	0.995
14:57280223:T:A	V250D	0.995
14:57280405:T:C	C311R	0.995
14:57282102:C:A	P321Q	0.995
14:57274813:A:T	E215V	0.994
14:57280411:T:G	Y313D	0.994
14:57286259:T:C	C444R	0.994
14:57288811:T:C	L467P	0.994
14:57274795:T:A	V209D	0.993
14:57274884:T:C	C239R	0.993
14:57282110:G:C	G324R	0.993
14:57282111:G:A	G324D	0.993
14:57282116:T:G	Y326D	0.993
14:57283121:T:C	F395S	0.993
14:57274860:T:A	W231R	0.991
14:57274860:T:C	W231R	0.991
14:57280370:T:C	F299S	0.991

dbSNP variants (sampled 300 via entrez): RS1000106258 (14:57289666 T>C), RS1000158968 (14:57284186 A>C), RS1000311889 (14:57277758 G>A,T), RS1000385233 (14:57291343 A>G), RS1000441974 (14:57283762 G>A,T), RS1000530734 (14:57294299 T>G), RS1000615977 (14:57280985 A>G,T), RS1000751256 (14:57270963 C>G), RS1000805020 (14:57271290 A>G), RS1000928666 (14:57293471 C>A,T), RS1000996064 (14:57289339 A>G), RS1001033987 (14:57268843 C>A,G), RS1001139858 (14:57268691 C>T), RS1001419727 (14:57292809 T>A,C), RS1001550797 (14:57290927 A>G)

Disease associations

OMIM: gene MIM:614368 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012496_4	Lung function (FVC)	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	7
trichostatin A	decreases expression	2
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
spiraeoside	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Topotecan	affects response to substance	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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