ABCA7

ATP binding cassette subfamily A member 7, the group of ATP binding cassette subfamily A

Basic information

Region (hg38): 19:1039997-1065572

Links

ENSG00000064687 ∙ NCBI:10347 ∙ OMIM:605414 ∙ HGNC:37 ∙ Uniprot:Q8IZY2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 26.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_019112.4	NP_061985.2	46	yes	-
ENST00000263094.11	ENSP00000263094.6	46	yes	-
ENST00000525073.6	ENSP00000432031.2	14	-	-
ENST00000612569.1	ENSP00000482948.1	6	-	-

Phenotypes

GenCC

Source: genCC

• Alzheimer disease 9 (Limited), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCA7 gene.

• not_specified (360 variants)
• not_provided (103 variants)
• ABCA7-related_disorder (41 variants)
• Alzheimer_disease_9 (32 variants)
• Flexion_contracture (3 variants)
• Neuromuscular_disease (2 variants)
• Primary_degenerative_dementia_of_the_Alzheimer_type,_presenile_onset (1 variants)
• Amyotrophic_lateral_sclerosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCA7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_019112.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	7	36	6	50
missense			360	39	9	408
nonsense	1	7	4	1		13
start loss						0
frameshift	1	9	9	2	1	22
splice donor/acceptor (+/-2bp)	1	4	8			13
Total	3	21	388	78	16

Highest pathogenic variant AF is 0.0001555391

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCA7	protein_coding	protein_coding	ENST00000263094	46	25470

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124312	2	1434	125748	0.00573

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.47	1516	1.36e+3	1.11	0.0000934	13509
Missense in Polyphen		521	481.43	1.0822		5228
Synonymous	-1.07	649	615	1.05	0.0000438	4708
Loss of Function	0.973	90	101	0.895	0.00000513	1043

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0214	0.0204
Ashkenazi Jewish	0.00929	0.00867
East Asian	0.00723	0.00693
Finnish	0.00343	0.00199
European (Non-Finnish)	0.00580	0.00518
Middle Eastern	0.00723	0.00693
South Asian	0.00428	0.00406
Other	0.00599	0.00539

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in phagocytosis by macrophages of apoptotic cells. Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells. May also mediate cholesterol efflux. May regulate cellular ceramide homeostasis during keratinocytes differentiation. {ECO:0000269|PubMed:12917409, ECO:0000269|PubMed:12925201, ECO:0000269|PubMed:14570867, ECO:0000269|PubMed:14592415}.
• Disease: DISEASE: Alzheimer disease 9 (AD9) [MIM:608907]: A familial, late- onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C- terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:25807283, ECO:0000269|PubMed:26141617}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: ABC transporters - Homo sapiens (human);ABC transporters in lipid homeostasis;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.155

Intolerance Scores

• loftool: 0.0339
• rvis_EVS: -2.15
• rvis_percentile_EVS: 1.46

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.392

Gene Damage Prediction

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

Gene ontology

• Biological process: lipid transport;phagocytosis;memory;positive regulation of cholesterol efflux;peptide cross-linking;cholesterol efflux;phospholipid efflux;high-density lipoprotein particle assembly;protein localization to nucleus;apolipoprotein A-I-mediated signaling pathway;negative regulation of amyloid precursor protein biosynthetic process;phospholipid translocation;positive regulation of phagocytosis;transmembrane transport;positive regulation of ERK1 and ERK2 cascade;positive regulation of amyloid-beta clearance;positive regulation of engulfment of apoptotic cell;negative regulation of amyloid-beta formation;positive regulation of phospholipid efflux
• Cellular component: Golgi membrane;phagocytic cup;Golgi apparatus;plasma membrane;cell surface;integral component of membrane;cell junction;early endosome membrane;ruffle membrane;ATP-binding cassette (ABC) transporter complex;intracellular membrane-bounded organelle
• Molecular function: transporter activity;lipid transporter activity;protein binding;ATP binding;ATPase activity;apolipoprotein A-I receptor activity;ATPase activity, coupled to transmembrane movement of substances;phosphatidylcholine-translocating ATPase activity;phosphatidylserine-translocating ATPase activity