AP4B1 (adaptor related protein complex 4 subunit beta 1)

Gene

• Entrez ID: 10717
• Gene name: Adaptor related protein complex 4 subunit beta 1
• Gene symbol: AP4B1
• Synonyms (NCBI Gene): BETA-4, CPSQ5, SPG47
• Chromosome: 1
• Chromosome location: 1p13.2
• Summary: This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1553259463	GACAT>-	Pathogenic	Intron variant, inframe indel, 5 prime UTR variant, non coding transcript variant, coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT046304	hsa-miR-23b-3p	CLASH	23622248
MIRT046304	hsa-miR-23b-3p	CLASH	23622248
MIRT043998	hsa-miR-378a-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	22472443, 25416956, 26542808, 26756312, 31515488, 32073997, 32296183, 33961781
GO:0005794	Component	Golgi apparatus	IEA
GO:0005802	Component	Trans-Golgi network	IDA	10066790
GO:0005802	Component	Trans-Golgi network	IEA
GO:0005802	Component	Trans-Golgi network	NAS	10436028
GO:0005829	Component	Cytosol	IDA	10066790
GO:0006605	Process	Protein targeting	IC	10066790
GO:0006605	Process	Protein targeting	IEA
GO:0006886	Process	Intracellular protein transport	IEA
GO:0008104	Process	Intracellular protein localization	IC	10066790
GO:0015031	Process	Protein transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0016192	Process	Vesicle-mediated transport	IBA
GO:0016192	Process	Vesicle-mediated transport	IEA
GO:0016192	Process	Vesicle-mediated transport	NAS	10436028
GO:0030117	Component	Membrane coat	IEA
GO:0030124	Component	AP-4 adaptor complex	IDA	10066790
GO:0030124	Component	AP-4 adaptor complex	NAS	10436028
GO:0030131	Component	Clathrin adaptor complex	IEA
GO:0030276	Function	Clathrin binding	IEA
GO:0031904	Component	Endosome lumen	TAS
GO:0032588	Component	Trans-Golgi network membrane	TAS
GO:0061938	Process	Protein localization to somatodendritic compartment	IEA
GO:0098541	Component	Cytoplasmic side of trans-Golgi network transport vesicle membrane	IDA	10066790

Other IDs

• MIM: 607245
• HGNC: 572
• e!Ensembl: ENSG00000134262

Protein

• UniProt ID: Q9Y6B7
• Protein name: AP-4 complex subunit beta-1 (AP-4 adaptor complex subunit beta) (Adaptor-related protein complex 4 subunit beta-1) (Beta subunit of AP-4) (Beta4-adaptin)
• 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: 2MJ7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01602	Adaptin_N	6 → 525	Adaptin N terminal region	Family
  PF09066	B2-adapt-app_C	621 → 731	Beta2-adaptin appendage, C-terminal sub-domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10436028}.
• Sequence:

  MPYLGSEDVVKELKKALCNPHIQADRLRYRNVIQRVIRYMTQGLDMSGVFMEMVKASATV
  DIVQKKLVYLYMCTYAPLKPDLALLAINTLCKDCSDPNPMVRGLALRSMCSLRMPGVQEY
  IQQPILNGLRDKASYVRRVAVLGCAKMHNLHGDSEVDGALVNELYSLLRDQDPIVVVNCL
  RSLEEILKQEGGVVINKPIAHHLLNRMSKLDQWGQAEVLNFLLRYQPRSEEELFDILNLL
  DSFLKSSSPGVVMGATKLFLILAKMFPHVQTDVLVRVKGPLLAACSSESRELCFVALCHV
  RQILHSLPGHFSSHYKKFFCSYSEPHYIKLQKVEVLCELVNDENVQQVLEELRGYCTDVS
  ADFAQAAIFAIGGIARTYTDQCVQILTELLGLRQEHITTVVVQTFRDLVWLCPQCTEAVC
  QALPGCEENIQDSEGKQALIWLLGVHGERIPNAPYVLEDFVENVKSETFPAVKMELLTAL
  LRLFLSRPAECQDMLGRLLYYCIEEEKDMAVRDRGLFYYRLLLVGIDEVKRILCSPKSDP
  TLGLLEDPAERPVNSWASDFNTLVPVYGKAHWATISKCQGAERCDPELPKTSSFAASGPL
  IPEENKERVQELPDSGALMLVPNRQLTADYFEKTWLSLKVAHQQVLPWRGEFHPDTLQMA
  LQVVNIQTIAMSRAGSRPWKAYLSAQDDTGCLFLTELLLEPGNSEMQISVKQNEARTETL
  NSFISVLETVIGTIEEIKS

• Sequence length: 739

Pathways

KEGG:

Lysosome

Reactome:

Lysosome Vesicle Biogenesis
Golgi Associated 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
Abnormal brain morphology	Likely pathogenic	rs1060499756, rs1060499771	RCV000454302 RCV000454309	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Abnormality of the nervous system	Likely pathogenic; Pathogenic	rs587779388	RCV001814068	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
AP4B1-related disorder	Likely pathogenic; Pathogenic	rs2526556797, rs529495094	RCV003976997 RCV003413550	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary spastic paraplegia	Likely pathogenic; Pathogenic	rs776976178	RCV001848851	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary spastic paraplegia 47	Likely pathogenic; Pathogenic	rs767220480, rs762612591, rs2101015147, rs771888480, rs114201291, rs745580319, rs777248758, rs2101035173, rs2101024933, rs2101025777, rs138335735, rs1013939776, rs2101044378, rs587779388, rs587783179, rs2526507579, rs755756363, rs2526557123, rs2526582013, rs2526632804, rs797045244, rs2526589151, rs879255396, rs773840258, rs2526583249, rs2526494351, rs2526581754, rs1367674744, rs1422502266, rs2526690923, rs776976178, rs1553257236, rs142209254, rs1553259463, rs374894037, rs529495094, rs1571563769, rs1667449135, rs746462207, rs1667419336	RCV001334571 RCV002539788 RCV001806369 RCV001815636 RCV001816566 RCV001822084 RCV002503345 RCV002222333 RCV001900134 RCV001941867 RCV001951281 RCV001953661 RCV002052046 RCV000144484 RCV000145019 RCV002282739 RCV003068427 RCV002801100 RCV002801101 RCV002828917 RCV000195189 RCV003017260 RCV001854921 RCV005012875 RCV003340821 RCV003388766 RCV003525469 RCV003527607 RCV003642232 RCV003827593 RCV000505223 RCV000502249 RCV005357821 RCV003525938 RCV000649277 RCV001855943 RCV001775007 RCV001199093 RCV001195992 RCV001211765 RCV001253044	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intellectual disability	Likely pathogenic; Pathogenic	rs587779388	RCV001251672	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spastic paraplegia	Pathogenic; Likely pathogenic	rs2101015147, rs777248758, rs2101035173, rs2101024858, rs1041267828, rs2101043631, rs2100998416, rs2100994885, rs2100997427, rs2100992189, rs2100995157, rs587779388, rs587783179, rs797045244, rs879255397, rs879255396, rs746890435, rs1060499756, rs1060499771, rs776976178, rs142209254, rs1553259463, rs374894037, rs529495094, rs1571563769, rs1667419336	RCV001849576 RCV001849775 RCV001849776 RCV001849777 RCV001849778 RCV001849779 RCV001849780 RCV001849781 RCV001849782 RCV001849783 RCV001849785 RCV001849316 RCV001849318 RCV001849337 RCV001849351 RCV001849350 RCV001849372 RCV001849374 RCV001849375 RCV001849381 RCV001849414 RCV001849408 RCV001849424 RCV001849437 RCV001849469 RCV001849481 RCV001849490	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AP-4 deficiency syndrome	Uncertain significance	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
BASAL CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL NEUROLOGIC ANOMALIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	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
SKIN NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 47, AUTOSOMAL RECESSIVE	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	33482886	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Hereditary Spastic Paraplegia	Spastic paraplegia	BEFREE	21440262		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	GWASCAT_DG	29059683		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	29035832		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral Hemorrhage	Cerebral hemorrhage	Pubtator	32166732	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Palsy	Cerebral palsy	Pubtator	21620353	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Palsy	Cerebral palsy	BEFREE	24065543		★☆☆☆☆ 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	32166732, 32171285	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	34521982	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	CLINVAR_DG	19559397, 20972249, 21620353, 22290197, 23167973, 23472171, 24395635, 24700674, 25552650, 25693842		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	32166732	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Henoch-Schoenlein Purpura	Henoch-Schonlein Nephritis	BEFREE	29193663		★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	BEFREE	21440262, 22290197		★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoxic-Ischemic Encephalopathy	Hypoxic-Ischemic Encephalopathy	BEFREE	24065543		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	21620353, 24781758, 32166732	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	BEFREE	22290197, 24700674, 24781758, 29430868		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Macrostomia	Macrostomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	29035832		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	27889644, 30674344		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	29430868		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	32166732	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neonatal Hypotonia	Hypotonia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	27889644, 30674344		★☆☆☆☆ Found in Text Mining only
Paraplegia	Paraplegia	Pubtator	32166732	Associate	★☆☆☆☆ Found in Text Mining only
Profound Mental Retardation	Mental retardation	BEFREE	29861105		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	32166732	Associate	★☆☆☆☆ Found in Text Mining only
Seizures Febrile	Seizures	Pubtator	32171285	Associate	★☆☆☆☆ 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	21620353, 22290197		★★☆☆☆ 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
Severe intellectual disability and progressive spastic paraplegia	Mental Retardation With Spastic Paraplegia	BEFREE	24781758, 29430868		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Paraplegia	Spastic Paraplegia	BEFREE	22290197, 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	CLINVAR_DG	21440262, 21620353, 22290197, 24781758		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 47, AUTOSOMAL RECESSIVE	Spastic Paraplegia	GENOMICS_ENGLAND_DG	22290197, 24700674		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 47, AUTOSOMAL RECESSIVE	Spastic Paraplegia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Paraplegia Hereditary	Hereditary spastic paraplegia	Pubtator	30337681, 31525725, 31915823, 32166732, 32979048, 34087981, 37482941	Associate	★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia, Hereditary	Spastic paraplegia	BEFREE	22554690		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Quadriplegia	Spastic Quadriplegia	BEFREE	24781758		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	11735040		★☆☆☆☆ 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