PSMD11

protein-coding

proteasome 26S subunit, non-ATPase 11, the group of 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. This gene encodes a member of the proteasome subunit S9 family that functions as a non-ATPase subunit of the 19S regulator and is phosphorylated by AMP-activated protein kinase. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

MANE transcript

NM_002815.4

Inheritance

ClinVar variants

P:3U:55B:1

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr17:32,444,379-32,483,319

External References & Databases

Ensembl (ENSG00000108671)

Transcript & Mutation Effects

hg38 • Region Span ~38.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PSMD11 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 18

Short statureTotal: 1

PSMD11-associated obesity and neurodevelopmental disorderTotal: 1

PSMD11-Related DisordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002815.4. 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			2 clinvar			2
missense		1 clinvar	46 clinvar	1 clinvar		48
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)	1 clinvar		4 clinvar			5
Total	2	1	55	1	0	59

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 96 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002815.4	RefSeq	NP_002806.2	13	MANE Select
ENST00000261712.8	Ensembl	ENSP00000261712.3	13	MANE Select
NM_001270482.2	RefSeq	NP_001257411.1	13	Standard
ENST00000457654.6	Ensembl	ENSP00000393185.2	13	Standard

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
TLR NFkB

Biological Process

ubiquitin-dependent protein catabolic process
protein deubiquitination
proteasome assembly
neutrophil degranulation
post-translational protein modification

Molecular Function

structural molecule activity
protein binding

Cellular Component

proteasome complex
extracellular region
nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261712
Coding exons: 13
Length: 39058
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.61	123	236	0.522	0.0000126	2739
Missense (PolyPhen)		15	53.642	0.27963		660
Synonymous	-0.297	93	89.4	1.04	0.00000471	807
Loss of Function	4.89	1	29.8	0.0335	0.00000180	325

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

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. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:22972301}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.197
RVIS EVS: -0.41
RVIS percentile EVS: 26.23

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.967

Gene Damage Prediction

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