RWDD3

RWD domain containing 3

Basic information

Region (hg38): 1:95234210-95247225

Links

ENSG00000122481 ∙ NCBI:25950 ∙ OMIM:615875 ∙ HGNC:21393 ∙ Uniprot:Q9Y3V2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RWDD3 gene.

• not_specified (31 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RWDD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015485.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	1		2
missense			27	2		29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	28	3	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RWDD3	protein_coding	protein_coding	ENST00000370202	4	13071

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00148	0.885	124707	0	87	124794	0.000349

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.299	123	133	0.927	0.00000612	1745
Missense in Polyphen		35	38.902	0.89971		565
Synonymous	0.179	50	51.6	0.968	0.00000272	494
Loss of Function	1.38	6	10.9	0.550	4.58e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00286	0.00281
Ashkenazi Jewish	0.00	0.00
East Asian	0.00172	0.00156
Finnish	0.00	0.00
European (Non-Finnish)	0.0000894	0.0000883
Middle Eastern	0.00172	0.00156
South Asian	0.000135	0.000131
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Enhancer of SUMO conjugation. Via its interaction with UBE2I/UBC9, increases SUMO conjugation to proteins by promoting the binding of E1 and E2 enzymes, thioester linkage between SUMO and UBE2I/UBC9 and transfer of SUMO to specific target proteins which include HIF1A, PIAS, NFKBIA, NR3C1 and TOP1. Isoform 1 and isoform 2 positively regulate the NF-kappa-B signaling pathway by enhancing the sumoylation of NF-kappa-B inhibitor alpha (NFKBIA), promoting its stabilization which consequently leads to an increased inhibition of NF-kappa-B transcriptional activity. Isoform 1 and isoform 2 negatively regulate the hypoxia-inducible factor-1 alpha (HIF1A) signaling pathway by increasing the sumoylation of HIF1A, promoting its stabilization, transcriptional activity and the expression of its target gene VEGFA during hypoxia. Isoform 2 promotes the sumoylation and transcriptional activity of the glucocorticoid receptor NR3C1 and enhances the interaction of SUMO1 and NR3C1 with UBE2I/UBC9. Has no effect on ubiquitination. {ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:23469069, ECO:0000269|PubMed:23508108}.
• Pathway: SUMO is transferred from E1 to E2 (UBE2I, UBC9);Post-translational protein modification;Metabolism of proteins;Processing and activation of SUMO;SUMOylation (Consensus)

Recessive Scores

• pRec: 0.0397

Intolerance Scores

• loftool: 0.785
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• pHI: 0.0301
• hipred: N
• hipred_score: 0.167
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0433

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rwdd3
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype

Gene ontology

• Biological process: negative regulation of NF-kappaB transcription factor activity;positive regulation of protein sumoylation;positive regulation of hypoxia-inducible factor-1alpha signaling pathway
• Cellular component: nucleus;cytoplasm
• Molecular function: protein binding