BANK1

protein-coding

B cell scaffold protein with ankyrin repeats 1, the group of Ankyrin repeat domain containing

Gene summary

The protein encoded by this gene is a B-cell-specific scaffold protein that functions in B-cell receptor-induced calcium mobilization from intracellular stores. This protein can also promote Lyn-mediated tyrosine phosphorylation of inositol 1,4,5-trisphosphate receptors. Polymorphisms in this gene are associated with susceptibility to systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

MANE transcript

NM_017935.5

Inheritance

—

ClinVar variants

U:140B:10

Top phenotype

systemic lupus erythematosus

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr4:101,411,286-102,074,812

External References & Databases

Ensembl (ENSG00000153064)

Transcript & Mutation Effects

hg38 • Region Span ~663.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

systemic lupus erythematosusSUPPORTIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0007915

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BANK1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 131

not providedTotal: 6

Systemic lupus erythematosusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017935.5. 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			1 clinvar	3 clinvar		4
missense			130 clinvar	7 clinvar		137
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	140	10	0	150

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017935.5	RefSeq	NP_060405.5	16	MANE Select
ENST00000322953.9	Ensembl	ENSP00000320509.4	16	MANE Select
NM_001083907.3	RefSeq	NP_001077376.3	15	Standard
NM_001127507.3	RefSeq	NP_001120979.3	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Biological Process

response to bacterium
B cell activation
positive regulation of MAPK cascade
negative regulation of translational initiation
positive regulation of peptidyl-tyrosine phosphorylation

Molecular Function

signaling receptor binding
protein tyrosine kinase binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322953
Coding exons: 16
Length: 663527
Individuals with no LoFs: 125573
Homozygous LoFs: 0
Heterozygous LoFs: 169
Defined: 125742
p: 0.000672

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.230	409	396	1.03	0.0000187	5200
Missense (PolyPhen)		125	121.6	1.028		1615
Synonymous	-0.295	136	132	1.03	0.00000619	1392
Loss of Function	2.45	25	42.1	0.593	0.00000231	535

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00043	0.00040	rare
Ashkenazi Jewish	0.0027	0.0026	notable
East Asian	0.00011	0.00011	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00082	0.00081	rare
South Asian	0.00084	0.00082	rare
Other	0.00083	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores. Promotes Lyn-mediated phosphorylation of IP3 receptors 1 and 2. {ECO:0000269|PubMed:11782428}.;
Disease: DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:18204447}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.998
RVIS EVS: 0.45
RVIS percentile EVS: 78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.816

Gene Damage Prediction

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