ABCA5
protein-codingATP binding cassette subfamily A member 5, 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, and White). This encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24, but neither the substrate nor the function of this gene is known. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0007610
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0008648
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0007610
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007610
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dermatologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ABCA5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_172232.4. 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 | 16 | 4 | 22 | ||
| missense | 1 | 209 | 17 | 4 | 231 | |
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 4 | 5 | |||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 2 | 7 | 216 | 33 | 8 | 266 |
Highest pathogenic variant AF is 0.00019096569
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_758424.1 | 38 | MANE Select | |
| Ensembl | ENSP00000376443.2 | 38 | MANE Select | |
| RefSeq | NP_061142.2 | 38 | Standard | |
| Ensembl | ENSP00000465351.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- ABC transporters - Homo sapiens (human)
- ABC transporters in lipid homeostasis
- Transport of small molecules
- ABC-family proteins mediated transport
Biological Process
- lipid transport
- negative regulation of macrophage derived foam cell differentiation
- cholesterol efflux
- high-density lipoprotein particle remodeling
- reverse cholesterol transport
Molecular Function
- lipid transporter activity
- ATP binding
- ATPase activity, coupled to transmembrane movement of substances
Cellular Component
- Golgi membrane
- lysosome
- lysosomal membrane
- late endosome
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392676
- Coding exons
- 38
- Length
- 82934
- Individuals with no LoFs
- 125515
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 230
- Defined
- 125747
- p
- 0.000923
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.374 | 748 | 777 | 0.962 | 0.0000369 | 10765 |
| Missense (PolyPhen) | 248 | 270.45 | 0.91698 | 3791 | ||
| Synonymous | -0.200 | 259 | 255 | 1.02 | 0.0000121 | 2972 |
| Loss of Function | 2.78 | 55 | 82.2 | 0.669 | 0.00000406 | 1162 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0013 | 0.0012 | notable |
| Latino/Admixed American | 0.0022 | 0.0018 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0.00047 | 0.00046 | rare |
| European (Non-Finnish) | 0.00073 | 0.00069 | rare |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.00056 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role in the processing of autolysosomes. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.0437
- RVIS EVS
- 0.77
- RVIS percentile EVS
- 86.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0698
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |