GeneBe

ABCC6

ATP binding cassette subfamily C member 6, the group of ATP binding cassette subfamily C

Basic information

Region (hg38): 16:16149565-16223522

Previous symbols: [ "ARA", "PXE" ]

Links

ENSG00000091262 ∙ NCBI:368 ∙ OMIM:603234 ∙ HGNC:57 ∙ Uniprot:O95255 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • inherited pseudoxanthoma elasticum (Definitive), mode of inheritance: Semidominant
  • autosomal recessive inherited pseudoxanthoma elasticum (Strong), mode of inheritance: AR
  • autosomal recessive inherited pseudoxanthoma elasticum (Definitive), mode of inheritance: AR
  • autosomal recessive inherited pseudoxanthoma elasticum (Supportive), mode of inheritance: AR
  • arterial calcification of infancy (Supportive), mode of inheritance: AD
  • arterial calcification, generalized, of infancy, 2 (Definitive), mode of inheritance: AR
  • autosomal recessive inherited pseudoxanthoma elasticum (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pseudoxanthoma elasticum (including Pseudoxanthoma elasticum, forme fruste)AD/AR/DigenicCardiovascular; Hematologic; OphthalmologicPreventive measures (eg, weight control, avoidance of smoking, and medical management of hypertension and hypercholesterolemia) related to cardiovascular risk factors may be beneficial by decreasing contributory factors related to atherosclerosis; Awareness may allow surveillance for and early detection and treatment of cardiovascular (eg, surgical interventions related to vascular disease) and hematologic manifestations (eg, interventions related to GI bleeding); Standard treatment for macular degeneration (including intraocular injection of anti-angiogenic drugs) may be beneficial, and awareness of ophthalmologic aspects may allow early detection and treatment; Circumstances such as contact sports and the use of medications that increase the risk of GI bleeding should be avoidedCardiovascular; Dermatologic; Hematologic; Ophthalmologic14068068; 3652487; 3342167; 2012127; 1600795; 8413390; 10619263; 10835643; 10835642; 10811882; 11209132; 15098239; 16086317; 18157818; 18800149; 19298904; 20034067; 20075945; 20301292; 21210805; 21386758; 21671388; 22209248; 23675997; 23746223; 23935882; 23968982; 23978319; 24008425; 24749718
In recessive forms, heterozygotes may have mild manifestations; Digenic inheritance (with GGCX) has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCC6 gene.

  • not_provided (1278 variants)
  • Autosomal_recessive_inherited_pseudoxanthoma_elasticum (704 variants)
  • Arterial_calcification,_generalized,_of_infancy,_2 (455 variants)
  • Pseudoxanthoma_elasticum,_forme_fruste (452 variants)
  • Inborn_genetic_diseases (167 variants)
  • ABCC6-related_disorder (90 variants)
  • not_specified (41 variants)
  • Retinal_dystrophy (13 variants)
  • See_cases (6 variants)
  • Pseudoxanthoma_elasticum (3 variants)
  • Optic_atrophy (2 variants)
  • Abnormality_of_the_eye (2 variants)
  • Papule (1 variants)
  • Finnish_congenital_nephrotic_syndrome (1 variants)
  • Cutis_laxa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCC6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001171.6. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
23
clinvar
352
clinvar
9
clinvar
 385
missense
40
clinvar
93
clinvar
654
clinvar
47
clinvar
7
clinvar
 841
nonsense
31
clinvar
31
clinvar
3
clinvar
 65
start loss
0
frameshift
43
clinvar
51
clinvar
3
clinvar
 97
splice donor/acceptor (+/-2bp)
11
clinvar
28
clinvar
8
clinvar
 47
Total 126 203 691 399 16

Highest pathogenic variant AF is 0.0016128413

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ABCC6protein_codingprotein_codingENST00000205557 3174595
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
12504007081257480.00282
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.099268371.110.00005319576
Missense in Polyphen222216.81.0242380
Synonymous-1.093913651.070.00002393223
Loss of Function1.366072.50.8280.00000361781

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002360.00235
Ashkenazi Jewish0.0001990.000198
East Asian0.004400.00436
Finnish0.004310.00431
European (Non-Finnish)0.003780.00376
Middle Eastern0.004400.00436
South Asian0.0009160.000915
Other0.002780.00277

dbNSFP

Source: dbNSFP

Function
FUNCTION: Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS). {ECO:0000269|PubMed:11880368}.;
Disease
DISEASE: Pseudoxanthoma elasticum (PXE) [MIM:264800]: A multisystem disorder characterized by accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Burch membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye including peau d'orange, angioid streaks, and choroidal neovascularizations, of the skin including soft, ivory colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces, and of the cardiovascular system with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings. {ECO:0000269|PubMed:10811882, ECO:0000269|PubMed:10835642, ECO:0000269|PubMed:10954200, ECO:0000269|PubMed:11427982, ECO:0000269|PubMed:11536079, ECO:0000269|PubMed:11702217, ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:15086542, ECO:0000269|PubMed:15098239, ECO:0000269|PubMed:15459974, ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515, ECO:0000269|PubMed:19339160, ECO:0000269|PubMed:20034067, ECO:0000269|PubMed:25615550}. Note=The disease is caused by mutations affecting the gene represented in this entry. Homozygous or compound heterozygous ABCC6 mutations have been found in the overwhelming majority of cases. Individuals carrying heterozygous mutations express limited manifestations of the pseudoxanthoma elasticum phenotype.; DISEASE: Arterial calcification of infancy, generalized, 2 (GACI2) [MIM:614473]: A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure. {ECO:0000269|PubMed:22209248}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
ABC transporters - Homo sapiens (human);Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Intolerance Scores

loftool
0.0194
rvis_EVS
0.63
rvis_percentile_EVS
83.54

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.159

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Zebrafish Information Network

Gene name
abcc6b.2
Affected structure
whole organism
Phenotype tag
abnormal
Phenotype quality
dead

Gene ontology

Biological process
visual perception;response to drug;transmembrane transport;ATP hydrolysis coupled anion transmembrane transport
Cellular component
nucleus;vacuolar membrane;endoplasmic reticulum membrane;plasma membrane;membrane;integral component of membrane;basolateral plasma membrane;apical plasma membrane;lateral plasma membrane
Molecular function
transporter activity;ATP binding;ATPase activity, coupled to transmembrane movement of substances;ATPase-coupled anion transmembrane transporter activity
Feedback | API | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.