BIN1

bridging integrator 1, the group of N-BAR domain containing

Basic information

Region (hg38): 2:127048026-127107288

Previous symbols: [ "AMPHL" ]

Links

ENSG00000136717 ∙ NCBI:274 ∙ OMIM:601248 ∙ HGNC:1052 ∙ Uniprot:O00499 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopathy, centronuclear, 2 (Definitive), mode of inheritance: AR
• myopathy, centronuclear, 2 (Moderate), mode of inheritance: AR
• autosomal recessive centronuclear myopathy (Supportive), mode of inheritance: AR
• autosomal dominant centronuclear myopathy (Supportive), mode of inheritance: AD
• myopathy, centronuclear, 2 (Strong), mode of inheritance: AR
• centronuclear myopathy (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, centronuclear, 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	17676042; 20142620; 22392505

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BIN1 gene.

• Myopathy, centronuclear, 2 (520 variants)
• not provided (159 variants)
• not specified (45 variants)
• Inborn genetic diseases (15 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BIN1 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			3	103	1	107
missense		2	205	6		213
nonsense	1	1	4			6
start loss						0
frameshift			3			3
inframe indel			5			5
splice donor/acceptor (+/-2bp)		1	5			6
splice region			18	29	1	48
non coding			29	107	66	202
Total	1	4	254	216	67

Variants in BIN1

This is a list of pathogenic ClinVar variants found in the BIN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-127048046-AT-A		Myopathy, centronuclear, 2	Uncertain significance (Jun 14, 2016)
2-127048056-T-G		Myopathy, centronuclear, 2	Uncertain significance (Jan 13, 2018)
2-127048077-C-T		Myopathy, centronuclear, 2	Uncertain significance (Jan 12, 2018)
2-127048108-G-A		Myopathy, centronuclear, 2	Uncertain significance (Jan 13, 2018)
2-127048113-C-T		Myopathy, centronuclear, 2	Uncertain significance (Jan 12, 2018)
2-127048223-T-C		Myopathy, centronuclear, 2	Uncertain significance (Jan 12, 2018)
2-127048225-G-A		Myopathy, centronuclear, 2	Uncertain significance (Jan 13, 2018)
2-127048279-C-A		Myopathy, centronuclear, 2	Uncertain significance (Jan 12, 2018)
2-127048283-A-C		Myopathy, centronuclear, 2	Uncertain significance (Jan 12, 2018)
2-127048312-C-T		Myopathy, centronuclear, 2	Uncertain significance (Jan 13, 2018)
2-127048332-G-A		Myopathy, centronuclear, 2	Uncertain significance (Jan 12, 2018)
2-127048444-G-A		Myopathy, centronuclear, 2	Uncertain significance (Jan 13, 2018)
2-127048444-G-T		Myopathy, centronuclear, 2	Benign/Likely benign (Nov 22, 2019)
2-127048471-C-T		Myopathy, centronuclear, 2	Uncertain significance (Jun 14, 2016)
2-127048504-G-A		Myopathy, centronuclear, 2	Uncertain significance (Jan 13, 2018)
2-127048525-G-A		Myopathy, centronuclear, 2	Conflicting classifications of pathogenicity (Oct 20, 2023)
2-127048530-G-A		Myopathy, centronuclear, 2	Uncertain significance (Dec 16, 2019)
2-127048534-C-A		Myopathy, centronuclear, 2	Uncertain significance (Jan 02, 2024)
2-127048535-C-T		Myopathy, centronuclear, 2	Likely benign (Oct 13, 2023)
2-127048537-T-C		Myopathy, centronuclear, 2	Uncertain significance (Jul 13, 2020)
2-127048542-G-A		Myopathy, centronuclear, 2	Uncertain significance (Jul 12, 2022)
2-127048552-C-T		Myopathy, centronuclear, 2	Uncertain significance (Aug 27, 2021)
2-127048553-G-A		Myopathy, centronuclear, 2	Likely benign (Mar 17, 2023)
2-127048556-G-A		Myopathy, centronuclear, 2	Likely benign (Jun 19, 2022)
2-127048557-A-G		Myopathy, centronuclear, 2	Uncertain significance (Aug 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BIN1	protein_coding	protein_coding	ENST00000316724	19	59329

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.778	0.222	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	235	354	0.663	0.0000222	3856
Missense in Polyphen		70	123.62	0.56625		1425
Synonymous	0.260	157	161	0.974	0.0000122	1132
Loss of Function	4.46	7	35.8	0.196	0.00000171	394

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000621	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000985	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in regulation of synaptic vesicle endocytosis. May act as a tumor suppressor and inhibits malignant cell transformation.
• Disease: DISEASE: Myopathy, centronuclear, 2 (CNM2) [MIM:255200]: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. {ECO:0000269|PubMed:17676042}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Endocytosis - Homo sapiens (human);VEGFA-VEGFR2 Signaling Pathway;Vesicle-mediated transport;endocytotic role of ndk phosphins and dynamin;Membrane Trafficking;p73 transcription factor network;Clathrin-mediated endocytosis;Arf6 trafficking events (Consensus)

Recessive Scores

• pRec: 0.202

Intolerance Scores

• loftool: 0.576
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.58

Haploinsufficiency Scores

• pHI: 0.226
• hipred: Y
• hipred_score: 0.722
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.980

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bin1
• Phenotype: immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); endocrine/exocrine gland phenotype; neoplasm; muscle 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: bin1b
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: endocytosis;nucleus organization;cytoskeleton organization;cell population proliferation;endosome to lysosome transport;viral process;regulation of endocytosis;positive regulation of actin filament polymerization;T-tubule organization;positive regulation of apoptotic process;regulation of neuron differentiation;positive regulation of astrocyte differentiation;nucleus localization;lipid tube assembly;membrane organization;regulation of cell cycle arrest;regulation of heart rate by cardiac conduction;negative regulation of potassium ion transmembrane transport;negative regulation of amyloid-beta formation;negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process;negative regulation of ventricular cardiac muscle cell action potential;negative regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
• Cellular component: nucleus;nuclear envelope;cytoplasm;cytosol;cytoskeleton;plasma membrane;synaptic vesicle;actin cytoskeleton;membrane;Z disc;T-tubule;axon;I band;node of Ranvier;axon initial segment;lipid tube
• Molecular function: protease binding;protein binding;phospholipid binding;clathrin binding;identical protein binding;tau protein binding;actin filament binding;chaperone binding;RNA polymerase binding