WAC

Chr 10p12.1

WW domain containing adaptor with coiled-coil

Aliases:: Wwp4, FLJ31290, PRO1741, BM-016, MGC10753
MANE:: ENST00000354911.9

OMIM: 615049 ↗NCBI: 51322 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

WAC · Q9BTA9

v62025-08-01

Predicted Aligned Error matrix for WAC — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

54.8/ 100

Low

647 residues

Confidence breakdown

Very high(≥ 90)12%
Confident(70–90)11%
Low(50–70)17%
Very low(< 50)61%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

10p11.21p12.31 microdeletion syndrome
0.73
DeSanto-Shinawi syndrome due to WAC point mutation
0.70
DeSanto-Shinawi syndrome
0.60
hereditary disease
0.51
Intellectual disability
0.49
neurodevelopmental disorder
0.41
Neurodevelopmental delay
0.34
Shwachman-Diamond syndrome
0.34
Neurodevelopmental abnormality
0.34
glomerulonephritis
0.30

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

WW domain-containing adapter protein with coiled-coil

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)