ABCA8

protein-coding

ATP binding cassette subfamily A member 8, the group of ATP binding cassette subfamily A

Gene summary

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The encoded protein may regulate lipid metabolism and be involved in the formation and maintenance of myelin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MANE transcript

NM_001288985.2

Inheritance

—

ClinVar variants

P:1U:255B:21

Top phenotype

Hypercholesterolemia, familial, 1

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr17:68,867,289-68,955,392

External References & Databases

Ensembl (ENSG00000141338)

Transcript & Mutation Effects

hg38 • Region Span ~88.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCA8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 251

not providedTotal: 11

Hypercholesterolemia, familial, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001288985.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar		5
missense			245 clinvar	14 clinvar	3 clinvar	262
nonsense						0
start loss			1 clinvar			1
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			6 clinvar		1 clinvar	7
Total	1	0	255	17	4	277

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001288985.2	RefSeq	NP_001275914.1	38	MANE Select
ENST00000586539.6	Ensembl	ENSP00000467271.1	38	MANE Select
NM_001288986.2	RefSeq	NP_001275915.1	38	Standard
NM_001375771.1	RefSeq	NP_001362700.1	37	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

ABC transporters - Homo sapiens (human)
Transport of small molecules
ABC-family proteins mediated transport

Biological Process

drug transmembrane transport
lipid transport
xenobiotic transport
transmembrane transport

Molecular Function

lipid transporter activity
ATP binding
xenobiotic transmembrane transporting ATPase activity
ATPase activity, coupled to transmembrane movement of substances

Cellular Component

plasma membrane
integral component of membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269080
Coding exons: 37
Length: 88101
Individuals with no LoFs: 123813
Homozygous LoFs: 29
Heterozygous LoFs: 1906
Defined: 125748
p: 0.00772

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.188	829	814	1.02	0.0000415	10347
Missense (PolyPhen)		236	234.73	1.0054		3245
Synonymous	0.668	297	312	0.952	0.0000174	2974
Loss of Function	0.129	80	81.3	0.985	0.00000393	1065

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0038	0.0037	notable
Latino/Admixed American	0.042	0.041	notable
Ashkenazi Jewish	0.0080	0.0080	notable
East Asian	0.0011	0.0011	notable
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.0024	0.0023	notable
South Asian	0.0019	0.0017	notable
Other	0.0085	0.0085	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ATP-dependent lipophilic drug transporter. {ECO:0000269|PubMed:12379217}.;

Intolerance Scores

LoFtool: 0.0951
RVIS EVS: 0.91
RVIS percentile EVS: 89.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.154

Gene Damage Prediction

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