CHMP1A

charged multivesicular body protein 1A, the group of Charged multivesicular body proteins|ESCRT-III associated factors

Basic information

Region (hg38): 16:89640815-89657738

Previous symbols: [ "PRSM1", "PCOLN3" ]

Links

ENSG00000131165 ∙ NCBI:5119 ∙ OMIM:164010 ∙ HGNC:8740 ∙ Uniprot:Q9HD42 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 8 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 8 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 8 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 8 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 8	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	Neurologic	23023333

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHMP1A gene.

• not provided (139 variants)
• Inborn genetic diseases (23 variants)
• not specified (19 variants)
• Pontocerebellar hypoplasia type 8 (8 variants)
• Pontocerebellar hypoplasia type 1A (1 variants)
• Intellectual disability (1 variants)
• Pontoneocerebellar hypoplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHMP1A 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			8	11	1	20
missense		1	28	2		31
nonsense		1				1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region	1		3	4	1	9
non coding			5	61	34	100
Total	1	3	42	74	35

Highest pathogenic variant AF is 0.0000263

Variants in CHMP1A

This is a list of pathogenic ClinVar variants found in the CHMP1A region.

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

Position	Type	Phenotype	Significance	ClinVar
16-89645630-A-C			Likely benign (Jun 16, 2018)
16-89645674-G-C			Likely benign (Jun 26, 2018)
16-89645730-T-G			Likely benign (Jun 28, 2018)
16-89645945-C-G		CHMP1A-related disorder	Likely benign (May 20, 2019)
16-89645957-G-A		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
16-89645966-A-C		not specified	Benign (May 11, 2016)
16-89645971-C-T		not specified • CHMP1A-related disorder	Benign (Mar 21, 2019)
16-89645972-G-A		not specified	Benign (May 11, 2016)
16-89645973-C-T		Pontocerebellar hypoplasia type 8	Uncertain significance (May 24, 2018)
16-89645998-G-C		CHMP1A-related disorder	Likely benign (Jun 01, 2023)
16-89646009-G-A		Inborn genetic diseases	Uncertain significance (May 18, 2023)
16-89646032-C-A		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
16-89646056-C-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
16-89646057-G-A		Inborn genetic diseases	Uncertain significance (May 04, 2021)
16-89646059-G-A		not specified	Likely benign (Oct 12, 2016)
16-89646070-T-C		Inborn genetic diseases	Uncertain significance (Sep 09, 2021)
16-89646080-C-G		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
16-89646088-C-G		not specified	Uncertain significance (Dec 23, 2021)
16-89646104-G-C			Likely benign (Jul 17, 2022)
16-89646107-C-G		not specified	Benign (Jan 26, 2024)
16-89646215-A-C			Likely benign (Sep 18, 2018)
16-89646325-C-T			Likely benign (Aug 17, 2018)
16-89646373-C-T			Likely benign (Aug 14, 2018)
16-89646481-C-T			Benign (Jun 26, 2018)
16-89646507-G-A			Likely benign (Sep 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHMP1A	protein_coding	protein_coding	ENST00000397901	7	13415

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000285	0.806	124635	0	10	124645	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.760	102	126	0.810	0.00000794	1274
Missense in Polyphen		23	43.846	0.52456		460
Synonymous	-1.31	70	57.4	1.22	0.00000426	365
Loss of Function	1.16	7	11.2	0.627	4.75e-7	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000167
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000359	0.0000354
Middle Eastern	0.000167	0.000167
South Asian	0.0000327	0.0000327
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable peripherally associated 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. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing. {ECO:0000269|PubMed:11559747, ECO:0000269|PubMed:11559748, ECO:0000269|PubMed:19129479, ECO:0000269|PubMed:23045692}.
• Disease: DISEASE: Pontocerebellar hypoplasia 8 (PCH8) [MIM:614961]: An autosomal recessive neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum. {ECO:0000269|PubMed:23023333}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocytosis - Homo sapiens (human);Necroptosis - Homo sapiens (human) (Consensus)

Intolerance Scores

• loftool: 0.233
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.51

Haploinsufficiency Scores

• pHI: 0.0880
• hipred: Y
• hipred_score: 0.507
• ghis: 0.487

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.149

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chmp1a

Zebrafish Information Network

• Gene name: chmp1a
• Affected structure: molecular layer valvula cerebelli
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: proteolysis;nucleus organization;mitotic chromosome condensation;mitotic metaphase plate congression;regulation of centrosome duplication;protein transport;vesicle-mediated transport;gene silencing;endosome transport via multivesicular body sorting pathway;multivesicular body assembly;viral budding via host ESCRT complex;late endosome to vacuole transport;negative regulation of cell cycle;negative regulation of transcription, DNA-templated;cell division;midbody abscission;regulation of mitotic spindle assembly;ESCRT III complex disassembly
• Cellular component: condensed nuclear chromosome;ESCRT III complex;early endosome;multivesicular body;microtubule organizing center;endomembrane system;nuclear matrix;extracellular exosome
• Molecular function: protein binding;metallopeptidase activity;zinc ion binding;protein domain specific binding;identical protein binding;protein homodimerization activity