PSMD12

proteasome 26S subunit, non-ATPase 12, the group of Proteasome

Basic information

Region (hg38): 17:67337916-67366605

Links

ENSG00000197170 ∙ NCBI:5718 ∙ OMIM:604450 ∙ HGNC:9557 ∙ Uniprot:O00232 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• Stankiewicz-Isidor syndrome (Strong), mode of inheritance: AD
• Stankiewicz-Isidor syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stankiewicz-Isidor syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	28132691

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMD12 gene.

• not_provided (49 variants)
• Inborn_genetic_diseases (45 variants)
• Stankiewicz-Isidor_syndrome (29 variants)
• PSMD12-related_disorder (12 variants)
• not_specified (4 variants)
• Intellectual_disability (2 variants)
• See_cases (2 variants)
• Neurodevelopmental_disorder (1 variants)
• Craniosynostosis_syndrome (1 variants)
• Spermatogenic_failure_18 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMD12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002816.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	2	6
missense			94	4	1	99
nonsense	10	5	1			16
start loss						0
frameshift	4	2	1			7
splice donor/acceptor (+/-2bp)	2	2				4
Total	16	9	96	8	3

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMD12	protein_coding	protein_coding	ENST00000356126	11	28712

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000159	125623	0	1	125624	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.87	163	246	0.664	0.0000124	2992
Missense in Polyphen		27	60.347	0.44741		770
Synonymous	1.70	67	87.1	0.769	0.00000447	825
Loss of Function	4.85	1	29.3	0.0341	0.00000172	341

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)	0.00000880	0.00000880
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. {ECO:0000269|PubMed:1317798}.
• Disease: DISEASE: Stankiewicz-Isidor syndrome (STISS) [MIM:617516]: A neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disorders, mild dysmorphism, ophthalmologic anomalies, feeding difficulties, deafness, and variable congenital malformations of the cardiac and/or urogenital systems. {ECO:0000269|PubMed:28132691}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Epstein-Barr virus infection - Homo sapiens (human);Proteasome - Homo sapiens (human);Proteasome Degradation;Parkin-Ubiquitin Proteasomal System pathway;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;TNFalpha;TLR JNK;TNF;Wnt Canonical;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.157
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.960
• hipred: Y
• hipred_score: 0.783
• ghis: 0.629

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.885

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmd12

Zebrafish Information Network

• Gene name: psmd12
• Affected structure: pronephric proximal convoluted tubule
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: protein deubiquitination;proteasome-mediated ubiquitin-dependent protein catabolic process;neutrophil degranulation;post-translational protein modification
• Cellular component: proteasome complex;extracellular region;nucleoplasm;cytoplasm;cytosol;proteasome regulatory particle;proteasome regulatory particle, lid subcomplex;membrane;proteasome accessory complex;nuclear proteasome complex;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen