PSMB1

proteasome 20S subunit beta 1, the group of Proteasome

Basic information

Region (hg38): 6:170535119-170553307

Links

ENSG00000008018 ∙ NCBI:5689 ∙ OMIM:602017 ∙ HGNC:9537 ∙ Uniprot:P20618 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly, hypotonia, and absent language (Limited), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, hypotonia, and absent language (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, hypotonia, and absent language	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	Musculoskeletal; Neurologic	32129449

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMB1 gene.

• Inborn genetic diseases (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMB1 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						0
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	0

Variants in PSMB1

This is a list of pathogenic ClinVar variants found in the PSMB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-170537323-T-C		not specified	Uncertain significance (Aug 02, 2021)
6-170543693-C-G		not specified	Uncertain significance (Jul 05, 2023)
6-170543726-T-C		not specified	Uncertain significance (Aug 12, 2021)
6-170543727-A-G		Neurodevelopmental disorder with microcephaly, hypotonia, and absent language	Pathogenic (Sep 15, 2022)
6-170549009-T-C		not specified	Uncertain significance (Dec 13, 2021)
6-170549033-G-A		not specified	Uncertain significance (Nov 10, 2022)
6-170549036-T-C		not specified	Uncertain significance (Dec 03, 2021)
6-170549100-T-C		not specified	Uncertain significance (Aug 01, 2022)
6-170549112-T-C		not specified	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMB1	protein_coding	protein_coding	ENST00000262193	6	18225

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.970	0.0300	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.875	109	138	0.790	0.00000737	1554
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Proteasome - Homo sapiens (human);Proteasome Degradation;TLR NFkB;Neutrophil degranulation;proteasome complex;B cell receptor signaling;Post-translational protein modification;Metabolism of proteins;DroToll-like;Notch;Hedgehog;Innate Immune System;Immune System;IL-1 NFkB;IL-1 p38;IL-1 JNK;TGF-beta super family signaling pathway canonical;TLR p38;UCH proteinases;Neddylation;Ub-specific processing proteases;JAK STAT pathway and regulation;Deubiquitination;TLR JNK;TNF;Wnt Canonical;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.335

Intolerance Scores

• loftool: 0.137
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.56

Haploinsufficiency Scores

• pHI: 0.922
• hipred: Y
• hipred_score: 0.783
• ghis: 0.576

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmb1

Zebrafish Information Network

• Gene name: psmb1
• Affected structure: anatomical system
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: proteasomal protein catabolic process;proteasomal ubiquitin-independent protein catabolic process;viral process;protein deubiquitination;proteasome-mediated ubiquitin-dependent protein catabolic process;neutrophil degranulation;post-translational protein modification
• Cellular component: proteasome complex;extracellular region;nucleus;nucleoplasm;cytoplasm;cytosol;proteasome core complex;proteasome core complex, beta-subunit complex;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: endopeptidase activity;threonine-type endopeptidase activity;protein binding