ABCC5
protein-codingATP binding cassette subfamily C member 5, the group of ATP binding cassette subfamily C
Gene summary
The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~98.0 kbGenCC 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 ABCC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005688.4. 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 | 1 | 1 | 4 | ||
| missense | 139 | 3 | 142 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 147 | 4 | 1 | 152 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005679.2 | 29 | MANE Select | |
| Ensembl | ENSP00000333926.6 | 29 | MANE Select | |
| RefSeq | NP_001018881.1 | 5 | Standard | |
| RefSeq | NP_001306961.1 | 20 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| abcc5 | Danio rerio | Structure: hematopoietic system Quality: has fewer parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- ABC transporters - Homo sapiens (human)
- Fluoropyrimidine Pathway, Pharmacokinetics
- Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics
- Pathway_PA165986194 -need delete
- Acetaminophen Pathway, Pharmacokinetics
Biological Process
- organic anion transport
- hyaluronan biosynthetic process
- transmembrane transport
- ATP hydrolysis coupled anion transmembrane transport
Molecular Function
- ATP binding
- organic anion transmembrane transporter activity
- ATPase activity, coupled to transmembrane movement of substances
- ATPase-coupled anion transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334444
- Coding exons
- 29
- Length
- 98082
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.60 | 537 | 829 | 0.648 | 0.0000482 | 9385 |
| Missense (PolyPhen) | 115 | 245.92 | 0.46763 | 2671 | ||
| Synonymous | 1.09 | 311 | 336 | 0.924 | 0.0000210 | 2899 |
| Loss of Function | 5.89 | 20 | 75.1 | 0.266 | 0.00000431 | 821 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a multispecific organic anion pump which can transport nucleotide analogs. {ECO:0000269|PubMed:10840050}.;
Recessive Scores
- pRec
- 0.359
Intolerance Scores
- LoFtool
- 0.146
- RVIS EVS
- -1.97
- RVIS percentile EVS
- 1.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.724
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |