protein
26S proteasome non-ATPase regulatory subunit 12
Gene
PSMD12
Organism
Homo sapiens(9606)
Length
456 aa
Mass
52,904 Da
PSMD12 encodes a non-ATPase regulatory subunit of the 26S proteasome, a large protein complex responsible for ATP-dependent degradation of ubiquitinated proteins (UniProt: O00232). This function is essential for maintaining protein homeostasis by removing misfolded, damaged, or functionally obsolete proteins. The proteasome thereby participates in critical cellular processes including cell cycle regulation, apoptosis, and DNA repair.
PSMD12 is expressed across tissues as a component of the proteasomal degradation pathway. Mutations in PSMD12 are associated with Stankiewicz-Isidor syndrome (STISS), a neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disturbances, mild dysmorphic features, ophthalmologic anomalies, feeding difficulties, deafness, and variable congenital cardiac or urogenital malformations.
PSMD12 is classified as a SFARI Category 2 (gene associated with autism) syndromic candidate (SFARI Cat 2), reflecting evidence linking proteasomal dysfunction to autism spectrum disorders in the context of broader developmental and systemic pathology. The syndromic classification indicates that autism features occur alongside other significant clinical manifestations in affected individuals.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
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
Disease associations
Stankiewicz-Isidor syndromeSTISS
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.
Sources
Last updated 5/6/2026, 5:23:54 AM