AP4M1 (adaptor related protein complex 4 subunit mu 1)

Gene

• Entrez ID: 9179
• Gene name: Adaptor related protein complex 4 subunit mu 1
• Gene symbol: AP4M1
• Synonyms (NCBI Gene): CPSQ3, MU-4, MU-ARP2, SPG50
• Chromosome: 7
• Chromosome location: 7q22.1
• Summary: This gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from t

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs141754568	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs146262009	C>G,T	Pathogenic	Stop gained, coding sequence variant, missense variant
rs369459721	C>G,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs730882249	C>T	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained
rs776788025	TG>-	Pathogenic	Coding sequence variant, frameshift variant
rs780030221	C>T	Pathogenic	Coding sequence variant, stop gained
rs1057521784	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1131691556	C>G,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs1191415115	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554380093	G>A	Pathogenic	Coding sequence variant, missense variant
rs1584514057	->G	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT788505	hsa-miR-1224-5p	CLIP-seq
MIRT788506	hsa-miR-1236	CLIP-seq
MIRT788507	hsa-miR-3074-5p	CLIP-seq
MIRT788508	hsa-miR-3199	CLIP-seq
MIRT788509	hsa-miR-4330	CLIP-seq
MIRT788510	hsa-miR-4676-5p	CLIP-seq
MIRT788511	hsa-miR-4722-3p	CLIP-seq
MIRT788512	hsa-miR-4740-5p	CLIP-seq
MIRT788513	hsa-miR-4751	CLIP-seq
MIRT788514	hsa-miR-4760-5p	CLIP-seq
MIRT788515	hsa-miR-575	CLIP-seq
MIRT788516	hsa-miR-668	CLIP-seq
MIRT788509	hsa-miR-4330	CLIP-seq
MIRT788510	hsa-miR-4676-5p	CLIP-seq
MIRT788515	hsa-miR-575	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000045	Process	Autophagosome assembly	IMP	29180427
GO:0005515	Function	Protein binding	IPI	25416956, 26496610, 26544806, 29180427, 32073997, 32296183, 33961781
GO:0005737	Component	Cytoplasm	IEA
GO:0005768	Component	Endosome	IEA
GO:0005769	Component	Early endosome	IEA
GO:0005769	Component	Early endosome	ISS
GO:0005794	Component	Golgi apparatus	IEA
GO:0005802	Component	Trans-Golgi network	IBA
GO:0005802	Component	Trans-Golgi network	IDA	20230749, 29180427, 32073997
GO:0005802	Component	Trans-Golgi network	NAS	10436028
GO:0005829	Component	Cytosol	IEA
GO:0006605	Process	Protein targeting	IBA
GO:0006605	Process	Protein targeting	IDA	20230749
GO:0006605	Process	Protein targeting	IEA
GO:0006622	Process	Protein targeting to lysosome	IDA	11139587
GO:0006886	Process	Intracellular protein transport	IEA
GO:0006886	Process	Intracellular protein transport	IMP	20230749, 29180427
GO:0006892	Process	Post-Golgi vesicle-mediated transport	TAS
GO:0006895	Process	Golgi to endosome transport	IMP	20230749
GO:0008104	Process	Intracellular protein localization	IEA
GO:0008104	Process	Intracellular protein localization	ISS
GO:0008320	Function	Protein transmembrane transporter activity	TAS
GO:0015031	Process	Protein transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0016192	Process	Vesicle-mediated transport	IEA
GO:0016192	Process	Vesicle-mediated transport	NAS	10436028
GO:0019904	Function	Protein domain specific binding	IDA	11139587, 26544806
GO:0030124	Component	AP-4 adaptor complex	IDA	10066790, 11802162, 29180427
GO:0030124	Component	AP-4 adaptor complex	NAS	10436028
GO:0030131	Component	Clathrin adaptor complex	IEA
GO:0031410	Component	Cytoplasmic vesicle	IBA
GO:0031904	Component	Endosome lumen	TAS
GO:0032588	Component	Trans-Golgi network membrane	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:0071806	Process	Protein transmembrane transport	IEA
GO:0090160	Process	Golgi to lysosome transport	IBA
GO:0090160	Process	Golgi to lysosome transport	IDA	11139587
GO:1903361	Process	Protein localization to basolateral plasma membrane	ISS

Other IDs

• MIM: 602296
• HGNC: 574
• e!Ensembl: ENSG00000221838

Protein

• UniProt ID: O00189
• Protein name: AP-4 complex subunit mu-1 (AP-4 adaptor complex mu subunit) (Adaptor-related protein complex 4 subunit mu-1) (Mu subunit of AP-4) (Mu-adaptin-related protein 2) (mu-ARP2) (Mu4-adaptin) (mu4)
• Protein function: Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (
• PDB: 3L81, 4MDR
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01217	Clat_adaptor_s	1 → 139	Clathrin adaptor complex small chain	Domain
  PF00928	Adap_comp_sub	173 → 453	Adaptor complexes medium subunit family	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous. Highly expressed in testis and lowly expressed in brain and lung. {ECO:0000269|PubMed:9013859}.
• Sequence:

  MISQFFILSSKGDPLIYKDFRGDSGGRDVAELFYRKLTGLPGDESPVVMHHHGRHFIHIR
  HSGLYLVVTTSENVSPFSLLELLSRLATLLGDYCGSLGEGTISRNVALVYELLDEVLDYG
  YVQTTSTEMLRNFIQTEAVVSKPFSLFDLSSVGLFGAETQQSKVAPSSAASRPVLSSRSD
  QSQKNEVFLDVVERLSVLIASNGSLLKVDVQGEIRLKSFLPSGSEMRIGLTEEFCVGKSE
  LRGYGPGIRVDEVSFHSSVNLDEFESHRILRLQPPQGELTVMRYQLSDDLPSPLPFRLFP
  SVQWDRGSGRLQVYLKLRCDLLSKSQALNVRLHLPLPRGVVSLSQELSSPEQKAELAEGA
  LRWDLPRVQGGSQLSGLFQMDVPGPPGPPSHGLSTSASPLGLGPASLSFELPRHTCSGLQ
  VRFLRLAFRPCGNANPHKWVRHLSHSDAYVIRI

• Sequence length: 453

Pathways

KEGG:

Lysosome

Reactome:

Lysosome Vesicle Biogenesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the nervous system	Pathogenic	rs2116614049	RCV001814408	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
AP4M1-related disorder	Likely pathogenic; Pathogenic	rs770705832, rs730882249	RCV003399328 RCV003390861	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Brain atrophy	Pathogenic	rs730882249	RCV000162190	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CNS hypomyelination	Pathogenic	rs730882249	RCV000162190	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Pathogenic	rs730882249	RCV000162190	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary spastic paraplegia	Pathogenic	rs369459721	RCV001849043	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary spastic paraplegia 50	Likely pathogenic; Pathogenic	rs770705832, rs1397027035, rs750783717, rs1796054104, rs772119268, rs2116643498, rs1350685858, rs1437455190, rs764326593, rs766513025, rs2116668499, rs730882249, rs372641895, rs973744863, rs146262009, rs2546956864, rs797045249, rs754498075, rs2546963629, rs2546963463, rs757055499, rs2546958669, rs2546946932, rs751742955, rs1131691556, rs1321353475, rs776788025, rs1554377262, rs1554380391, rs780030221, rs369459721, rs1584507780, rs1562912305, rs777220438, rs1796279189	RCV001810068 RCV001972645 RCV001977862 RCV001986821 RCV001971834 RCV001912274 RCV002019358 RCV001955502 RCV002267591 RCV002267593 RCV002273188 RCV000191923 RCV003062717 RCV003110761 RCV000191922 RCV002828579 RCV000193994 RCV001040211 RCV002918352 RCV003140480 RCV003479661 RCV003506953 RCV003876279 RCV003871514 RCV003114618 RCV003507288 RCV000696462 RCV000534458 RCV000549259 RCV000626141 RCV000680158 RCV000991382 RCV001249634 RCV001879998 RCV001261614	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hypoplasia of the corpus callosum	Pathogenic	rs730882249	RCV000162190	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Likely pathogenic; Pathogenic	rs797045249, rs369459721, rs1562912305, rs777220438, rs1437308674	RCV001251673 RCV001260899 RCV001260896 RCV001260895 RCV001260900	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microcephaly	Pathogenic	rs730882249	RCV000162190	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spastic paraplegia	Likely pathogenic; Pathogenic	rs770705832, rs777377185, rs2116638409, rs2116670931, rs1344550427, rs1584514057, rs371712994, rs2116616864, rs730882249, rs146262009, rs754498075, rs752598529, rs1057521784, rs1321353475, rs1554380391, rs780030221, rs369459721, rs1562912305, rs1796176171	RCV001849519 RCV001849786 RCV001849787 RCV001849789 RCV001849790 RCV001849791 RCV001849792 RCV001849793 RCV001849324 RCV001849336 RCV001849338 RCV001849358 RCV001849370 RCV001849397 RCV001849402 RCV001849421 RCV001849426 RCV001849470 RCV001849488 RCV001280532	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AP-4 deficiency syndrome	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar ClinGen, GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
AP4-RELATED INTELLECTUAL DISABILITY AND SPASTIC PARAPLEGIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL NEUROLOGIC ANOMALIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL RETARDATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE INTELLECTUAL DISABILITY AND PROGRESSIVE SPASTIC PARAPLEGIA	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 50, AUTOSOMAL RECESSIVE	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	33712570	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	29777097		★☆☆☆☆ Found in Text Mining only
Atrophy	Atrophy	Pubtator	29096665	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Hereditary Spastic Paraplegia	Spastic paraplegia	BEFREE	29096665		★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Primary Microcephaly	Primary microcephaly	Pubtator	28464862	Associate	★☆☆☆☆ Found in Text Mining only
Brain atrophy	Brain atrophy	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar hypoplasia	Pubtator	29096665	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral Palsy	Cerebral palsy	BEFREE	19559397, 21620353, 25496299		★☆☆☆☆ Found in Text Mining only
Cerebral Palsy	Cerebral palsy	Pubtator	19559397, 21620353, 25496299	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Palsy	Cerebral palsy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Class III malocclusion	Malocclusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	32319648	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	25496299	Associate	★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Dysplasia Of The Hip	Developmental dysplasia of the hip	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital genu recurvatum	Congenital genu recurvatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	29096665	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	BEFREE	25496299		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	36371792	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Head and Neck Neoplasms	Head and neck neoplasm	Pubtator	25496299	Associate	★☆☆☆☆ Found in Text Mining only
Henoch-Schoenlein Purpura	Henoch-Schonlein Nephritis	BEFREE	29096665		★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	21620353, 25496299, 29096665, 36371792	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intellectual Disability	Mental retardation	CTD_human_DG	21937992		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intellectual Disability	Mental retardation	BEFREE	29430868		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Macrostomia	Macrostomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mental deficiency	Mental retardation	CTD_human_DG	21937992		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	28464862	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly	Microcephaly	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial Complex III Deficiency	Mitochondrial complex deficiency	Pubtator	25496299	Associate	★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	CLINVAR_DG	19559397, 20972249, 21620353, 21937992, 23167973, 23472171, 24395635, 24700674, 24781758, 25496299, 25552650		★☆☆☆☆ Found in Text Mining only
Neonatal Hypotonia	Hypotonia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	29096665		★☆☆☆☆ Found in Text Mining only
Paraparesis Spastic	Paraparesis	Pubtator	25496299	Associate	★☆☆☆☆ Found in Text Mining only
Paraplegia	Paraplegia	Pubtator	36371792	Associate	★☆☆☆☆ Found in Text Mining only
Profound Mental Retardation	Mental retardation	CTD_human_DG	21937992		★☆☆☆☆ Found in Text Mining only
Seizures Febrile	Seizures	Pubtator	29096665	Associate	★☆☆☆☆ Found in Text Mining only
Severe Congenital Microcephaly	Congenital Microcephaly	BEFREE	28464862		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	BEFREE	21620353		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability and progressive spastic paraplegia	Mental Retardation With Spastic Paraplegia	ORPHANET_DG	19559397		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe intellectual disability and progressive spastic paraplegia	Mental Retardation With Spastic Paraplegia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Paraplegia	Spastic Paraplegia	BEFREE	30337681		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Spastic Paraplegia	Spastic Paraplegia	HPO_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SPASTIC PARAPLEGIA 2, X-LINKED (disorder)	Hereditary spastic paraplegia	BEFREE	30337681		★☆☆☆☆ Found in Text Mining only
SPASTIC PARAPLEGIA 47, AUTOSOMAL RECESSIVE	Spastic Paraplegia	BEFREE	31525725		★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia 50 Autosomal Recessive	Spastic paraplegia	Pubtator	30337681, 36371792	Associate	★☆☆☆☆ Found in Text Mining only
SPASTIC PARAPLEGIA 51, AUTOSOMAL RECESSIVE	Spastic Paraplegia	BEFREE	31525725		★☆☆☆☆ Found in Text Mining only
SPASTIC PARAPLEGIA 52, AUTOSOMAL RECESSIVE	Spastic Paraplegia	BEFREE	31525725		★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia Hereditary	Hereditary spastic paraplegia	Pubtator	29096665, 30337681, 31525725, 31915823, 32979048, 34087981, 37482941	Associate	★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia, Hereditary	Spastic paraplegia	BEFREE	29096665, 31525725		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Paraplegia-50, Autosomal Recessive	Spastic paraplegia	GENOMICS_ENGLAND_DG	19559397, 29096665		★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia-50, Autosomal Recessive	Spastic paraplegia	BEFREE	31525725		★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia-50, Autosomal Recessive	Spastic paraplegia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia-50, Autosomal Recessive	Spastic paraplegia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Spastic Quadriplegia	Spastic Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only