HERC2

Chr 15q13.1

HECT and RLD domain containing E3 ubiquitin protein ligase 2

Aliases:: jdf2, p528, D15F37S1
MANE:: ENST00000261609.13

OMIM: 605837 ↗NCBI: 8924 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

HERC2 · O95714

Mean pLDDT

Not published

AlphaFold has not published a prediction for this sequence. This is common for very long proteins.

Confidence breakdown

Check AlphaFold DB

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

developmental delay with autism spectrum disorder and gait instability
0.76
Prader-Willi syndrome
0.44
eye color
0.39
hair color
0.38
neurodevelopmental disorder
0.38
retinal disorder
0.35
Motor delay
0.34
Global brain atrophy
0.34
Severe intellectual disability
0.34
Autosomal dominant optic atrophy, classic type
0.34

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

Protein function (UniProt)

E3 ubiquitin-protein ligase HERC2

E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). Also modulates iron metabolism by regulating the basal turnover of FBXL5 (PubMed:24778179)