DDRGK1

Chr 20p13

DDRGK domain containing 1

Aliases:: dJ1187M17.3, UFBP1
MANE:: ENST00000354488.8

OMIM: 616177 ↗NCBI: 65992 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

DDRGK1 · Q96HY6

v62025-08-01

Predicted Aligned Error matrix for DDRGK1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

74.6/ 100

Confident

314 residues

Confidence breakdown

Very high(≥ 90)39%
Confident(70–90)27%
Low(50–70)13%
Very low(< 50)21%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

spondyloepimetaphyseal dysplasia, Shohat type
0.63
neurodegenerative disease
0.53
hereditary disease
0.19
hyperphosphatasia-intellectual disability syndrome
0.12
chronic hepatitis C virus infection
0.11
risk-taking behaviour
0.10
metabolic dysfunction-associated steatotic liver disease
0.08
Parkinson disease
0.08
gastric cancer
0.08
neoplasm
0.07

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

Protein function (UniProt)

DDRGK domain-containing protein 1

Component of the UFM1 ribosome E3 ligase (UREL) complex, a multiprotein complex that catalyzes ufmylation of endoplasmic reticulum-docked proteins (PubMed:30626644, PubMed:32160526, PubMed:35753586, PubMed:36121123, PubMed:36543799, PubMed:37595036, PubMed:37795761, PubMed:38383785, PubMed:38383789). The UREL complex plays a key role in ribosome recycling by mediating mono-ufmylation of the RPL26/uL24 subunit of the 60S ribosome following ribosome dissociation: ufmylation weakens the junction between post-termination 60S subunits and SEC61 translocons, promoting release and recycling of the large ribosomal subunit from the endoplasmic reticulum membrane (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 and subsequent 60S ribosome recycling either take place after normal termination of translation or after ribosome stalling during cotranslational translocation at the endoplasmic reticulum (PubMed:37595036, PubMed:38383785, PubMed:38383789). Within the UREL complex, DDRGK1 tethers the complex to the endoplasmic reticulum membrane to restrict its activity to endoplasmic reticulum-docked ribosomes and acts as an ufmylation 'reader': following RPL26/uL24 ufmylation, DDRGK1 specifically binds to ufmylated RPL26/uL24 via its UFIM motif, resulting in stable association between the 60S ribosome and the UREL complex, followed by dissociation of the 60S ribosome subunit from the endoplasmic reticulum membrane (PubMed:36121123, PubMed:37595036, PubMed:38383785, PubMed:38383789). The UREL complex is also involved in reticulophagy in response to endoplasmic reticulum stress by promoting ufmylation of proteins such as CYB5R3 and RPN1, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:32160526, PubMed:36543799). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability (PubMed:28128204, PubMed:32160526). Acts as a regulator of immunity by promoting differentiation of B-cells into plasma cells: acts by promoting expansion of the endoplasmic reticulum and regulating the unfolded protein response (UPR) (By similarity). May also be required for TRIP4 ufmylation (PubMed:25219498). May play a role in NF-kappa-B-mediated transcription through regulation of the phosphorylation and the degradation of NFKBIA, the inhibitor of NF-kappa-B (PubMed:23675531). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186). Required for stabilization and ufmylation of ATG9A (By similarity)