CHMP2B

charged multivesicular body protein 2B, the group of Charged multivesicular body proteins|ESCRT-III

Basic information

Region (hg38): 3:87227270-87255556

Links

ENSG00000083937 ∙ NCBI:25978 ∙ OMIM:609512 ∙ HGNC:24537 ∙ Uniprot:Q9UQN3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (Strong), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis type 17 (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (Limited), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (Strong), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7; Dementia, familial, nonspecific	AD	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	Neurologic	8541850; 12451202; 16041373; 16954699; 16807408; 17956895; 20352044; 20592581; 21222599; 22422914; 23142962; 23155438

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHMP2B gene.

• Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (101 variants)
• not provided (34 variants)
• not specified (12 variants)
• Frontotemporal dementia (9 variants)
• CHMP2B-related condition (8 variants)
• Combined Pituitary Hormone Deficiency, Recessive (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHMP2B 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			1	14	4	19
missense		1	35	3		39
nonsense			1			1
start loss			1			1
frameshift			3			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			3	3	1	7
non coding			22	14	12	48
Total	0	1	65	31	16

Highest pathogenic variant AF is 0.00000658

Variants in CHMP2B

This is a list of pathogenic ClinVar variants found in the CHMP2B region.

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

Position	Type	Phenotype	Significance	ClinVar
3-87227318-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Jan 13, 2018)
3-87227372-C-A		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Benign/Likely benign (Oct 05, 2018)
3-87227379-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Jan 13, 2018)
3-87227421-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Benign/Likely benign (Aug 10, 2018)
3-87227485-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Jan 12, 2018)
3-87227489-G-A		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Apr 27, 2017)
3-87227524-T-C		not specified	Uncertain significance (Aug 26, 2022)
3-87227543-G-A		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Likely benign (Mar 08, 2021)
3-87227549-C-T		not specified • Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Benign (Jan 31, 2024)
3-87227550-G-A		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Dec 30, 2022)
3-87227554-A-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Aug 19, 2022)
3-87227562-T-C		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (May 22, 2023)
3-87227563-T-A			Likely benign (May 18, 2018)
3-87227564-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 • not specified	Benign (Mar 01, 2024)
3-87227570-C-G		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Likely benign (Jul 03, 2023)
3-87240690-T-G		not specified	Uncertain significance (Mar 08, 2017)
3-87240692-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 • CHMP2B-related disorder	Benign/Likely benign (Dec 06, 2023)
3-87240720-G-A		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 • CHMP2B-related disorder	Conflicting classifications of pathogenicity (Feb 05, 2024)
3-87240728-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 • CHMP2B-related disorder	Conflicting classifications of pathogenicity (Sep 27, 2023)
3-87240731-G-A		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Feb 14, 2023)
3-87240735-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Apr 19, 2022)
3-87240746-A-G		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Aug 17, 2023)
3-87240749-A-G		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Jun 25, 2023)
3-87240752-A-G		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 • CHMP2B-related disorder	Conflicting classifications of pathogenicity (Dec 18, 2023)
3-87240754-A-C		Frontotemporal dementia and/or amyotrophic lateral sclerosis 7	Uncertain significance (Nov 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHMP2B	protein_coding	protein_coding	ENST00000263780	6	28278

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000462	0.649	125656	0	92	125748	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.339	103	113	0.910	0.00000571	1413
Missense in Polyphen		37	38.594	0.9587		532
Synonymous	0.144	34	35.1	0.969	0.00000177	375
Loss of Function	0.980	10	14.0	0.717	8.89e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00526	0.00527
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000109	0.000109
South Asian	0.000165	0.000163
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4.
• Disease: DISEASE: Frontotemporal dementia, chromosome 3-linked (FTD3) [MIM:600795]: Characterized by an onset of dementia in the late 50's initially characterized by behavioral and personality changes including apathy, restlessness, disinhibition and hyperorality, progressing to stereotyped behaviors, non-fluent aphasia, mutism and dystonia, with a marked lack of insight. The brains of individuals with FTD3 have no distinctive neuropathological features. They show global cortical and central atrophy, but no beta-amyloid deposits. {ECO:0000269|PubMed:16041373}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amyotrophic lateral sclerosis 17 (ALS17) [MIM:614696]: An adult-onset progressive neurodegenerative disorder with predominantly lower motor neuron involvement, manifest as muscle weakness and wasting of the upper and lower limbs, bulbar signs, and respiratory insufficiency. {ECO:0000269|PubMed:16807408, ECO:0000269|PubMed:20352044}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocytosis - Homo sapiens (human);Necroptosis - Homo sapiens (human);Disease;Vesicle-mediated transport;Membrane Trafficking;Budding and maturation of HIV virion;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;Endosomal Sorting Complex Required For Transport (ESCRT);Infectious disease (Consensus)

Recessive Scores

• pRec: 0.146

Intolerance Scores

• loftool: 0.591
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.348
• hipred: Y
• hipred_score: 0.765
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.922

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chmp2b
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: autophagy;nucleus organization;endosome organization;mitotic metaphase plate congression;regulation of centrosome duplication;protein transport;endosomal transport;macroautophagy;viral life cycle;endosome transport via multivesicular body sorting pathway;multivesicular body assembly;viral budding via host ESCRT complex;late endosome to vacuole transport;cognition;multivesicular body-lysosome fusion;midbody abscission;neuron cellular homeostasis;regulation of modification of postsynaptic structure;regulation of postsynapse organization;regulation of mitotic spindle assembly;positive regulation of viral release from host cell;ESCRT III complex disassembly
• Cellular component: ESCRT III complex;cytoplasm;lysosome;endosome;late endosome;multivesicular body;cytosol;plasma membrane;postsynaptic density;late endosome membrane;extracellular exosome;glutamatergic synapse
• Molecular function: protein binding;protein domain specific binding;cadherin binding