DDRGK1

DDRGK domain containing 1

Basic information

Region (hg38): 20:3190349-3204685

Previous symbols: [ "C20orf116" ]

Links

ENSG00000198171 ∙ NCBI:65992 ∙ OMIM:616177 ∙ HGNC:16110 ∙ Uniprot:Q96HY6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia, Shohat type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepimetaphyseal dysplasia, Shohat type	AR	Pulmonary	The condition may include a narrow trachea resulting in upper airway obstruction, and awareness may allow interventions to decrease morbidity and mortality	Musculoskeletal; Pulmonary	28263186

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDRGK1 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDRGK1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				20	4	24
missense			51	3	3	57
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			2	7	1	10
non coding				13	6	19
Total	1	1	51	36	13

Highest pathogenic variant AF is 0.00000657

Variants in DDRGK1

This is a list of pathogenic ClinVar variants found in the DDRGK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-3190662-G-A			Likely benign (Oct 05, 2023)
20-3190681-C-T		Inborn genetic diseases	Likely benign (Sep 17, 2021)
20-3190691-C-T			Benign (Jan 31, 2024)
20-3190692-G-A			Likely benign (Oct 23, 2023)
20-3190694-T-C		Inborn genetic diseases	Uncertain significance (Dec 05, 2022)
20-3190715-C-T			Uncertain significance (Apr 07, 2023)
20-3190722-G-A			Likely benign (Jun 30, 2023)
20-3190724-C-T			Uncertain significance (Mar 02, 2022)
20-3190727-T-C		Inborn genetic diseases	Uncertain significance (Nov 28, 2023)
20-3190736-G-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2021)
20-3190751-T-A			Uncertain significance (Dec 01, 2021)
20-3190762-A-G			Uncertain significance (Sep 19, 2022)
20-3190763-C-T		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
20-3190764-G-A			Likely benign (Jan 05, 2024)
20-3190775-C-T		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
20-3190787-T-C		Inborn genetic diseases	Uncertain significance (May 23, 2023)
20-3190805-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2023)
20-3190805-G-T			Likely benign (May 14, 2022)
20-3190822-G-T			Uncertain significance (Jul 07, 2023)
20-3190836-G-A			Likely benign (Jan 11, 2024)
20-3191225-C-T			Uncertain significance (Jul 05, 2022)
20-3191226-G-A			Uncertain significance (Mar 02, 2022)
20-3191241-A-G			Uncertain significance (Jul 26, 2021)
20-3191248-G-A			Likely benign (Jan 18, 2024)
20-3191251-C-G			Likely benign (Jun 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDRGK1	protein_coding	protein_coding	ENST00000354488	9	14336

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.07e-7	0.778	125716	0	31	125747	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.557	173	195	0.888	0.0000130	1966
Missense in Polyphen		82	88.104	0.93072		848
Synonymous	0.761	67	75.4	0.888	0.00000434	643
Loss of Function	1.35	13	19.4	0.669	0.00000114	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000548	0.0000544
Finnish	0.0000947	0.0000924
European (Non-Finnish)	0.0000988	0.0000967
Middle Eastern	0.0000548	0.0000544
South Asian	0.000489	0.000457
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein which interacts with the E3 UFM1-protein ligase UFL1 and one of its substrates TRIP4 and is required for TRIP4 ufmylation. Through TRIP4 ufmylation may regulate nuclear receptors-mediated transcription (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). May also play a role in the cellular response to endoplasmic reticulum stress (By similarity). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186). {ECO:0000250|UniProtKB:Q80WW9, ECO:0000269|PubMed:23675531, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:28263186}.
• Disease: DISEASE: Spondyloepimetaphyseal dysplasia, Shohat type (SEMDSH) [MIM:602557]: An autosomal recessive skeletal dysplasia that affects cartilage development. It is characterized by vertebral, epiphyseal, and metaphyseal abnormalities, including scoliosis with vertebral compression fractures, flattened vertebral bodies, and hypomineralization of long bones. Affected individuals may exhibit a small trunk, short neck, small limbs, joint laxity, bowlegs, and/or abdominal distension with hepatosplenomegaly. {ECO:0000269|PubMed:28263186}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0868

Intolerance Scores

• loftool: 0.678
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.76

Haploinsufficiency Scores

• pHI: 0.0547
• hipred: Y
• hipred_score: 0.626
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.818

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ddrgk1
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype

Zebrafish Information Network

• Gene name: ddrgk1
• Affected structure: ceratobranchial cartilage
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: positive regulation of cell population proliferation;positive regulation of gene expression;negative regulation of gene expression;positive regulation of cell migration;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of intracellular estrogen receptor signaling pathway;response to endoplasmic reticulum stress;negative regulation of apoptotic process;positive regulation of transcription by RNA polymerase II;positive regulation of NF-kappaB transcription factor activity;cartilage development;positive regulation of proteasomal protein catabolic process;positive regulation of cell cycle G1/S phase transition;positive regulation of I-kappaB phosphorylation;positive regulation of metallopeptidase activity;positive regulation of protein localization to endoplasmic reticulum;positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding;protein K69-linked ufmylation
• Cellular component: nucleolus;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane
• Molecular function: RNA polymerase II repressing transcription factor binding;protein binding;ubiquitin-like protein ligase binding