AP4B1

adaptor related protein complex 4 subunit beta 1, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|Adaptor related protein complex 4

Basic information

Region (hg38): 1:113894194-113905712

Previous symbols: [ "SPG47" ]

Links

ENSG00000134262 ∙ NCBI:10717 ∙ OMIM:607245 ∙ HGNC:572 ∙ Uniprot:Q9Y6B7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 47 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 47 (Moderate), mode of inheritance: AR
• hereditary spastic paraplegia 47 (Strong), mode of inheritance: AR
• AP4-related intellectual disability and spastic paraplegia (Supportive), mode of inheritance: AR
• AP-4 deficiency syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 47, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	21620353; 22290197; 24700674; 24781758

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP4B1 gene.

• Hereditary spastic paraplegia 47 (27 variants)
• Spastic paraplegia (11 variants)
• not provided (8 variants)
• Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP4B1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	62	3	70
missense		1	189	8	2	200
nonsense	11	5				16
start loss			2			2
frameshift	17	5	1			23
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	2				5
splice region			5	7		12
non coding			2	37	9	48
Total	31	13	201	107	14

Highest pathogenic variant AF is 0.0000395

Variants in AP4B1

This is a list of pathogenic ClinVar variants found in the AP4B1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-113894764-A-G			Likely benign (Oct 27, 2018)
1-113895074-T-C		Hereditary spastic paraplegia 47	Uncertain significance (Aug 09, 2022)
1-113895085-T-C		Hereditary spastic paraplegia 47	Likely benign (Jan 18, 2024)
1-113895106-A-G		Hereditary spastic paraplegia 47	Likely benign (Dec 13, 2022)
1-113895120-C-G		Inborn genetic diseases	Uncertain significance (Nov 22, 2016)
1-113895123-T-C		Hereditary spastic paraplegia 47	Uncertain significance (May 10, 2022)
1-113895129-G-A			Uncertain significance (Jun 01, 2018)
1-113895134-C-T		Hereditary spastic paraplegia 47	Likely benign (Nov 26, 2020)
1-113895135-G-A		Hereditary spastic paraplegia 47	Uncertain significance (Jun 06, 2022)
1-113895140-T-A		Inborn genetic diseases • Hereditary spastic paraplegia 47	Likely benign (Aug 28, 2023)
1-113895151-GTTTCACAGAGA-G		Hereditary spastic paraplegia 47	Uncertain significance (Dec 30, 2021)
1-113895154-T-G		Hereditary spastic paraplegia 47	Uncertain significance (Jan 20, 2021)
1-113895186-T-A		Hereditary spastic paraplegia 47	Uncertain significance (Aug 16, 2022)
1-113895191-T-C			Likely benign (May 02, 2018)
1-113895202-T-G		Hereditary spastic paraplegia 47	Uncertain significance (Aug 20, 2022)
1-113895203-T-A		Hereditary spastic paraplegia 47	Uncertain significance (Aug 24, 2021)
1-113895206-G-T		Inborn genetic diseases	Uncertain significance (May 23, 2023)
1-113895219-G-A		Hereditary spastic paraplegia 47	Uncertain significance (Mar 27, 2022)
1-113895245-T-C		Hereditary spastic paraplegia 47	Likely benign (Dec 02, 2022)
1-113895250-A-C		not specified	Uncertain significance (Jan 21, 2015)
1-113895255-C-T		Hereditary spastic paraplegia 47	Uncertain significance (Apr 23, 2022)
1-113895265-C-A		Hereditary spastic paraplegia 47	Uncertain significance (Apr 02, 2021)
1-113895272-C-T		Inborn genetic diseases	Uncertain significance (Jul 18, 2016)
1-113895274-T-C		Inborn genetic diseases	Uncertain significance (Jan 31, 2017)
1-113895278-G-A		Inborn genetic diseases • Hereditary spastic paraplegia 47	Likely benign (Jul 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP4B1	protein_coding	protein_coding	ENST00000369569	10	10454

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.34e-9	0.987	125609	0	139	125748	0.000553

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.131	398	405	0.982	0.0000227	4813
Missense in Polyphen		127	136.44	0.93078		1680
Synonymous	-0.0565	152	151	1.01	0.00000796	1469
Loss of Function	2.37	20	35.1	0.569	0.00000206	389

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00101
Ashkenazi Jewish	0.000993	0.000993
East Asian	0.000217	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000660	0.000659
Middle Eastern	0.000217	0.000217
South Asian	0.000653	0.000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin- associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}.
• Pathway: Lysosome - Homo sapiens (human);Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.939
• rvis_EVS: -0.13
• rvis_percentile_EVS: 44.03

Haploinsufficiency Scores

• pHI: 0.171
• hipred: N
• hipred_score: 0.367
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.975

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	Medium
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Ap4b1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: protein targeting;protein localization;vesicle-mediated transport
• Cellular component: trans-Golgi network;cytosol;extrinsic component of membrane;AP-4 adaptor complex;clathrin adaptor complex;endosome lumen;trans-Golgi network membrane
• Molecular function: protein binding;clathrin binding