ABCB6

ATP binding cassette subfamily B member 6 (Langereis blood group), the group of ATP binding cassette subfamily B|Blood group antigens

Basic information

Region (hg38): 2:219209771-219218994

Links

ENSG00000115657 ∙ NCBI:10058 ∙ OMIM:605452 ∙ HGNC:47 ∙ Uniprot:Q9NP58 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microphthalmia, isolated, with coloboma 7 (Limited), mode of inheritance: AD
• microphthalmia, isolated, with coloboma 7 (Limited), mode of inheritance: AD
• dyschromatosis universalis hereditaria (Supportive), mode of inheritance: AD
• familial pseudohyperkalemia (Supportive), mode of inheritance: AD
• microphthalmia, isolated, with coloboma (Supportive), mode of inheritance: AD
• dyschromatosis universalis hereditaria 3 (Limited), mode of inheritance: AD
• microphthalmia, isolated, with coloboma 7 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pseudohyperkalemia, familial, 2, due to red cell leak; Blood group, Langereis system	AD/BG	Hematologic	Variants related to Familial pseudohyperkalemia may be important related to transfusion management; Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	Dermatologic; Hematologic; Ophthalmologic	5790273; 22246506; 22226084; 23180570; 23519333; 24947683

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCB6 gene.

• not provided (95 variants)
• Inborn genetic diseases (34 variants)
• Acute intermittent porphyria (9 variants)
• Protoporphyria, erythropoietic, 1 (8 variants)
• Variegate porphyria (6 variants)
• ABCB6-related condition (6 variants)
• Hereditary coproporphyria (5 variants)
• not specified (4 variants)
• Microphthalmia, isolated, with coloboma 7 (2 variants)
• Familial pseudohyperkalemia (2 variants)
• Langereis blood group (2 variants)
• Microphthalmia, isolated, with coloboma 7;Dyschromatosis universalis hereditaria 3;Langereis blood group;Familial pseudohyperkalemia (1 variants)
• Dyschromatosis universalis hereditaria 3;Microphthalmia, isolated, with coloboma 7;Langereis blood group;Familial pseudohyperkalemia (1 variants)
• Microphthalmia, isolated, with coloboma 7;Familial pseudohyperkalemia;Dyschromatosis universalis hereditaria 3 (1 variants)
• Langereis blood group;Familial pseudohyperkalemia;Microphthalmia, isolated, with coloboma 7;Dyschromatosis universalis hereditaria 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCB6 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				14	2	16
missense		1	72	7	3	83
nonsense			2	1		3
start loss						0
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding			1	4	15	20
Total	0	1	79	26	20

Variants in ABCB6

This is a list of pathogenic ClinVar variants found in the ABCB6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-219209957-G-A			Uncertain significance (Nov 28, 2023)
2-219209988-C-T		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
2-219210002-C-A			Uncertain significance (Jun 17, 2022)
2-219210018-C-A		Inborn genetic diseases	Uncertain significance (Apr 26, 2023)
2-219210036-G-C		Microphthalmia, isolated, with coloboma 7	Pathogenic (Jan 13, 2012)
2-219210042-C-T		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
2-219210071-T-A			Benign (May 10, 2021)
2-219210125-G-A			Benign (May 10, 2021)
2-219210235-C-T			Likely benign (Apr 05, 2018)
2-219210255-C-T		ABCB6-related disorder	Uncertain significance (Aug 07, 2023)
2-219210277-A-G		ABCB6-related disorder	Likely benign (Jan 22, 2024)
2-219210291-T-A		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
2-219210323-T-C			Benign (Nov 10, 2018)
2-219210369-G-A			Benign (Feb 26, 2023)
2-219210375-C-T			Uncertain significance (Apr 26, 2023)
2-219210382-T-C			Uncertain significance (Nov 29, 2021)
2-219210394-C-T		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
2-219210405-C-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
2-219210418-C-A			Conflicting classifications of pathogenicity (Jun 22, 2023)
2-219210419-T-G		ABCB6-related disorder	Uncertain significance (Oct 25, 2022)
2-219210471-G-A		Inborn genetic diseases	Uncertain significance (May 24, 2023)
2-219210709-A-C		Langereis blood group	Affects (Jan 15, 2012)
2-219210751-C-T			Uncertain significance (Aug 23, 2022)
2-219210752-G-A		ABCB6-related disorder	Uncertain significance (Nov 16, 2023)
2-219210765-G-C			Likely benign (Jan 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCB6	protein_coding	protein_coding	ENST00000265316	19	9223

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.60e-19	0.347	125411	0	337	125748	0.00134

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.139	507	498	1.02	0.0000299	5354
Missense in Polyphen		189	184.3	1.0255		2008
Synonymous	-1.55	234	206	1.14	0.0000125	1788
Loss of Function	1.68	35	47.5	0.737	0.00000264	455

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00504	0.00500
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.00191	0.00190
Finnish	0.00126	0.00125
European (Non-Finnish)	0.00102	0.000932
Middle Eastern	0.00191	0.00190
South Asian	0.000803	0.000719
Other	0.00118	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds heme and porphyrins and functions in their ATP- dependent uptake into the mitochondria. Plays a crucial role in heme synthesis. {ECO:0000269|PubMed:10837493, ECO:0000269|PubMed:17006453}.
• Disease: DISEASE: Microphthalmia, isolated, with coloboma, 7 (MCOPCB7) [MIM:614497]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269|PubMed:22226084}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dyschromatosis universalis hereditaria 3 (DUH3) [MIM:615402]: An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications. {ECO:0000269|PubMed:23519333, ECO:0000269|PubMed:24224009, ECO:0000269|PubMed:24498303, ECO:0000269|PubMed:25288164}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pseudohyperkalemia, familial, 2, due to red cell leak (PSHK2) [MIM:609153]: A dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape. {ECO:0000269|PubMed:23180570, ECO:0000269|PubMed:24947683}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ABC transporters - Homo sapiens (human);Transport of small molecules;ABC-family proteins mediated transport;Mitochondrial ABC transporters (Consensus)

Intolerance Scores

• loftool: 0.165
• rvis_EVS: -0.37
• rvis_percentile_EVS: 28.26

Haploinsufficiency Scores

• pHI: 0.124
• hipred: N
• hipred_score: 0.251
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.558

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Abcb6
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: abcb6a
• Affected structure: pupil
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: porphyrin-containing compound biosynthetic process;cellular iron ion homeostasis;brain development;heme transport;skin development;transmembrane transport
• Cellular component: Golgi membrane;nucleoplasm;mitochondrion;mitochondrial envelope;mitochondrial outer membrane;endosome;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;cytosol;plasma membrane;endosome membrane;integral component of mitochondrial outer membrane;ATP-binding cassette (ABC) transporter complex;extracellular exosome
• Molecular function: ATP binding;heme transporter activity;heme-transporting ATPase activity;efflux transmembrane transporter activity;heme binding