protein
WW domain-containing adapter protein with coiled-coil
Gene
WAC
Organism
Homo sapiens(9606)
Length
647 aa
Mass
70,724 Da
WAC (WW domain-containing adapter protein with coiled-coil) is a 647-amino acid protein that functions as a molecular linker between transcriptional machinery and chromatin-modifying complexes (UniProt: Q9BTA9). It interacts with RNA polymerase II via its WW domain and with the RNF20-RNF40 ubiquitin ligase complex via its coiled-coil region, thereby regulating histone H2B monoubiquitination and gene transcription. WAC also regulates autophagy pathways and positively controls mTOR activity through assembly of the TTT-RUVBL protein complex (UniProt: Q9BTA9).
WAC is associated with DeSanto-Shinawi syndrome (DESSH), an autosomal dominant condition characterized by developmental delay, hypotonia, seizures, and distinctive dysmorphic features including broad forehead, synophrys, depressed nasal bridge, and hearing loss, along with eye abnormalities, feeding difficulties, and sleep disturbances (UniProt: Q9BTA9).
WAC is classified as a syndromic autism spectrum disorder risk gene by the SFARI Gene database (SFARI Cat 1), indicating its role in syndromic forms of ASD associated with developmental and neurological dysfunction.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
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
Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation-induced autophagy (PubMed:22354037). Also acts as a negative regulator of basal autophagy (PubMed:26812014). Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). May negatively regulate the ubiquitin proteasome pathway (PubMed:21329877)
Disease associations
DeSanto-Shinawi syndromeDESSH
An autosomal dominant syndrome characterized by developmental delay, hypotonia, behavioral problems, eye abnormalities, constipation, feeding difficulties, seizures and sleep problems. Patients exhibit dysmorphic features, including broad/prominent forehead, synophrys and/or bushy eyebrows, depressed nasal bridge and bulbous nasal tip. Additional variable features are posteriorly rotated ears, hirsutism, deep-set eyes, thin upper lip, inverted nipples, hearing loss and branchial cleft anomalies.
Sources
Last updated 5/6/2026, 5:25:07 AM