PSMB1

protein-coding

proteasome 20S subunit beta 1, the group of Proteasome

Gene summary

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is tightly linked to the TBP (TATA-binding protein) gene in human and in mouse, and is transcribed in the opposite orientation in both species. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002793.4

Inheritance

ClinVar variants

P:1U:26B:2

Top phenotype

Neurodevelopmental disorder with microcephaly, hypotonia, and absent language

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr6:170,535,120-170,553,307

External References & Databases

Ensembl (ENSG00000008018)

Transcript & Mutation Effects

hg38 • Region Span ~18.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with microcephaly, hypotonia, and absent languageLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859287

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

neurodevelopmental disorder with microcephaly, hypotonia, and absent languageLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859287

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with microcephaly, hypotonia, and absent languageAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 32129449

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PSMB1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 24

Neurodevelopmental disorder with microcephaly, hypotonia, and absent languageTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002793.4. 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			1 clinvar			1
missense	1 clinvar		24 clinvar	2 clinvar		27
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	26	2	0	29

Highest pathogenic variant AF is 0.0000013759341

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002793.4	RefSeq	NP_002784.1	6	MANE Select
ENST00000262193.7	Ensembl	ENSP00000262193.6	6	MANE Select
ENST00000892690.1	Ensembl	ENSP00000562749.1	6	Standard
ENST00000892691.1	Ensembl	ENSP00000562750.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
psmb1	Danio rerio	Structure: anatomical system Quality: quality abnormal

Gene / Model

Organism

Observed Phenotype

psmb1

Danio rerio

Structure: anatomical system

Quality: quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Proteasome - Homo sapiens (human)
Proteasome Degradation
TLR NFkB
Neutrophil degranulation
proteasome complex

Biological Process

proteasomal protein catabolic process
proteasomal ubiquitin-independent protein catabolic process
viral process
protein deubiquitination
proteasome-mediated ubiquitin-dependent protein catabolic process

Molecular Function

endopeptidase activity
threonine-type endopeptidase activity
protein binding

Cellular Component

proteasome complex
extracellular region
nucleus
nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262193
Coding exons: 6
Length: 18225
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.875	109	138	0.790	0.00000737	1554
Missense (PolyPhen)		18	45.186	0.39835		494
Synonymous	-0.374	58	54.5	1.06	0.00000308	486
Loss of Function	3.05	0	10.8	0.00	5.20e-7	139

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}.;

Recessive Scores

pRec: 0.335

Intolerance Scores

LoFtool: 0.137
RVIS EVS: 0.17
RVIS percentile EVS: 65.56

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.903

Gene Damage Prediction

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