PSMC6

protein-coding

proteasome 26S subunit, ATPase 6, the group of AAA ATPases|Proteasome

Gene summary

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. Pseudogenes have been identified on chromosomes 8 and 12. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002806.5

Inheritance

—

ClinVar variants

U:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr14:52,707,178-52,728,590

External References & Databases

Ensembl (ENSG00000100519)

Transcript & Mutation Effects

hg38 • Region Span ~21.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PSMC6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002806.5. 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			1
missense			9 clinvar			9
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	13	0	0	13

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002806.5	RefSeq	NP_002797.4	14	MANE Select
ENST00000445930.7	Ensembl	ENSP00000401802.3	14	MANE Select
NM_001366414.2	RefSeq	NP_001353343.1	10	Standard
ENST00000553798.5	Ensembl	ENSP00000451241.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
psmc6	Danio rerio	Structure: anatomical system Quality: quality abnormal

Gene / Model

Organism

Observed Phenotype

psmc6

Danio rerio

Structure: anatomical system

Quality: quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Epstein-Barr virus infection - Homo sapiens (human)
Proteasome - Homo sapiens (human)
Proteasome Degradation
Parkin-Ubiquitin Proteasomal System pathway
Post-translational protein modification

Biological Process

ubiquitin-dependent protein catabolic process
protein deubiquitination
ubiquitin-dependent ERAD pathway
post-translational protein modification
positive regulation of RNA polymerase II transcriptional preinitiation complex assembly

Molecular Function

protein binding
ATP binding
ATPase activity
protein binding, bridging
proteasome-activating ATPase activity

Cellular Component

proteasome complex
nucleus
nucleoplasm
cytosol
proteasome regulatory particle, base subcomplex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000445930
Coding exons: 14
Length: 21416
Individuals with no LoFs: 125554
Homozygous LoFs: 2
Heterozygous LoFs: 191
Defined: 125747
p: 0.000768

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.32	85	225	0.377	0.0000115	2633
Missense (PolyPhen)		11	72.223	0.15231		868
Synonymous	0.157	73	74.7	0.977	0.00000373	746
Loss of Function	4.32	2	25.6	0.0782	0.00000134	320

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0062	0.0061	notable
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.0021	0.0021	notable
European (Non-Finnish)	0.00030	0.00030	rare
South Asian	0.000065	0.000033	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC6 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798}.;

Intolerance Scores

LoFtool: 0.118
RVIS EVS: -0.12
RVIS percentile EVS: 44.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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