ABCB5

protein-coding

ATP binding cassette subfamily B member 5, the group of ATP binding cassette subfamily B

Gene summary

ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005 [PubMed 15760339]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001163941.2

Inheritance

ClinVar variants

U:208B:20

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr7:20,615,667-20,777,038

External References & Databases

Ensembl (ENSG00000004846)

Transcript & Mutation Effects

hg38 • Region Span ~161.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence-(AR assessment): No published cases with confirmed autosomal recessive inheritance Published Genetic Evidence= 0 Our cases: Family1: 1 proband with homozygous frameshift. + consanguinity. AR inheritance. No additional affected relatives. No segregation or case-control data. Case-level points (default for predicted null) = 1.0 point (AR predicted/proven null = 1.5, −0.5 downgrade for consanguinity); segregation = 0; case-control = 0. Genetic Evidence our cases=1 Genetic evidence total = 1.0 / 12 Experimental evidence: expression reported in brain/BBB tissue only (PMID: 25647612) = 0.5; Non-human model organism = 2.0 (PMID: 25030174) Experimental evidence total = 2.5 / 6 Overall score = 1.5 points

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCB5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 211

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001163941.2. 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	4 clinvar		6
missense			203 clinvar	13 clinvar	3 clinvar	219
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	208	17	3	228

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001163941.2	RefSeq	NP_001157413.1	27	MANE Select
ENST00000404938.7	Ensembl	ENSP00000384881.2	27	MANE Select
NM_001163942.2	RefSeq	NP_001157414.1	3	Standard
NM_001163993.3	RefSeq	NP_001157465.1	3	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
cell differentiation
regulation of membrane potential
xenobiotic transport
compound eye corneal lens development

Molecular Function

ATP binding
xenobiotic transmembrane transporting ATPase activity
efflux transmembrane transporter activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000404938
Coding exons: 27
Length: 161829
Individuals with no LoFs: 106790
Homozygous LoFs: 3319
Heterozygous LoFs: 15639
Defined: 125748
p: 0.0785

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.98	814	670	1.22	0.0000350	8173
Missense (PolyPhen)		282	233.18	1.2093		2815
Synonymous	-2.13	279	237	1.18	0.0000131	2420
Loss of Function	0.683	60	66.0	0.909	0.00000391	797

Population LoF Frequency

Population	CAF	p-value	Status
African	0.044	0.040	notable
Latino/Admixed American	0.24	0.21	notable
Ashkenazi Jewish	0.026	0.025	notable
East Asian	0.50	0.43	notable
Finnish	0.087	0.083	notable
European (Non-Finnish)	0.0081	0.0076	notable
South Asian	0.089	0.079	notable
Other	0.062	0.056	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug doxorubicin. Specifically present in limbal stem cells, where it plays a key role in corneal development and repair. {ECO:0000269|PubMed:12960149, ECO:0000269|PubMed:15205344, ECO:0000269|PubMed:15899824, ECO:0000269|PubMed:22306008}.;

Recessive Scores

pRec: 0.0931

Intolerance Scores

LoFtool: 0.0314
RVIS EVS: 4.18
RVIS percentile EVS: 99.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.130

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High