PSMD14

proteasome 26S subunit, non-ATPase 14, the group of Proteasome|JAMM/MPN+ metallopeptidase family

Basic information

Region (hg38): 2:161308425-161411717

Links

ENSG00000115233

∙ NCBI:10213 ∙ OMIM:607173 ∙ HGNC:16889 ∙ Uniprot:O00487 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMD14 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMD14 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			4 clinvar			4
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	4	0	0

Variants in PSMD14

This is a list of pathogenic ClinVar variants found in the PSMD14 region.

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

Position	Phenotype	Significance	ClinVar
2-161367778-C-A		Benign (May 26, 2018)	718397
2-161391140-A-G	not specified	Uncertain significance (Dec 14, 2021)	2266983
2-161391156-G-A	not specified	Uncertain significance (Jan 31, 2024)	3220435
2-161395199-A-G	not specified	Uncertain significance (Nov 07, 2022)	2220648
2-161411389-G-A	not specified	Uncertain significance (Jun 21, 2021)	2365170

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMD14	protein_coding	protein_coding	ENST00000409682	10	103680

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.977	0.0234	124563	0	2	124565	0.00000803

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.57	29	153	0.189	0.00000735	2035
Missense in Polyphen		10	69.51	0.14386		901
Synonymous	1.46	37	50.1	0.738	0.00000247	550
Loss of Function	3.47	1	15.9	0.0627	6.76e-7	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000886	0.00000885
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 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. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non- homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:22909820, ECO:0000269|PubMed:9374539}.;
Pathway: Epstein-Barr virus infection - Homo sapiens (human);Proteasome - Homo sapiens (human);Parkin-Ubiquitin Proteasomal System pathway;Neutrophil degranulation;proteasome complex;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Metalloprotease DUBs;UCH proteinases;Neddylation;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

pRec: 0.281

Intolerance Scores

loftool: 0.369
rvis_EVS: 0.01
rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

pHI: 0.967
hipred: Y
hipred_score: 0.825
ghis: 0.684

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	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Psmd14
Phenotype

Gene ontology

Biological process: double-strand break repair via homologous recombination;double-strand break repair via nonhomologous end joining;ubiquitin-dependent protein catabolic process;positive regulation of endopeptidase activity;protein deubiquitination;proteasome-mediated ubiquitin-dependent protein catabolic process;neutrophil degranulation;post-translational protein modification;response to ethanol;regulation of proteasomal protein catabolic process;protein K63-linked deubiquitination
Cellular component: proteasome complex;extracellular region;nucleus;nucleoplasm;cytosol;proteasome regulatory particle, lid subcomplex;proteasome accessory complex;cytosolic proteasome complex;secretory granule lumen;ficolin-1-rich granule lumen
Molecular function: thiol-dependent ubiquitin-specific protease activity;protein binding;metallopeptidase activity;thiol-dependent ubiquitinyl hydrolase activity;metal ion binding;endopeptidase activator activity;Lys63-specific deubiquitinase activity;proteasome binding