WDR26

WD repeat domain 26, the group of MicroRNA protein coding host genes|WD repeat domain containing

Basic information

Region (hg38): 1:224385146-224437033

Links

ENSG00000162923 ∙ NCBI:80232 ∙ OMIM:617424 ∙ HGNC:21208 ∙ Uniprot:Q9H7D7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Skraban-Deardorff syndrome (Definitive), mode of inheritance: AD
• Skraban-Deardorff syndrome (Strong), mode of inheritance: AD
• Skraban-Deardorff syndrome (Strong), mode of inheritance: AD
• Skraban-Deardorff syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Skraban-Deardorff syndrome	AD	General	Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Musculoskeletal; Neurologic	28686853

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR26 gene.

• not_provided (96 variants)
• Inborn_genetic_diseases (64 variants)
• Skraban-Deardorff_syndrome (59 variants)
• WDR26-related_disorder (14 variants)
• not_specified (8 variants)
• Long_QT_syndrome (2 variants)
• Intellectual_disability (2 variants)
• Neurofibromatosis,_type_1 (1 variants)
• See_cases (1 variants)
• Intellectual_disability,_seizures,_abnormal_gait_and_distinctive_facial_features (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR26 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379403.1. 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	14	3	18
missense	2	14	120	10		146
nonsense	8	1				9
start loss						0
frameshift	25	2	1			28
splice donor/acceptor (+/-2bp)	4	2				6
Total	39	19	122	24	3

Highest pathogenic variant AF is 0.000002478321

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDR26	protein_coding	protein_coding	ENST00000414423	14	51891

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000368	125568	0	10	125578	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.58	169	361	0.469	0.0000193	4291
Missense in Polyphen		17	90.64	0.18755		1027
Synonymous	1.38	117	138	0.850	0.00000713	1313
Loss of Function	5.48	0	35.0	0.00	0.00000183	412

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: G-beta-like protein involved in cell signal transduction (PubMed:15378603, PubMed:19446606, PubMed:22065575, PubMed:23625927, PubMed:27098453, PubMed:26895380). Acts as a negative regulator in MAPK signaling pathway (PubMed:15378603). Functions as a scaffolding protein to promote G beta:gamma- mediated PLCB2 plasma membrane translocation and subsequent activation in leukocytes (PubMed:22065575, PubMed:23625927). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). Acts as a negative regulator of the canonical Wnt signaling pathway through preventing ubiquitination of beta-catenin CTNNB1 by the beta- catenin destruction complex, thus negatively regulating CTNNB1 degradation (PubMed:27098453). Serves as a scaffold to coordinate PI3K/AKT pathway-driven cell growth and migration (PubMed:26895380). Protects cells from oxidative stress-induced apoptosis via the down-regulation of AP-1 transcriptional activity as well as by inhibiting cytochrome c release from mitochondria (PubMed:19446606). Protects also cells by promoting hypoxia- mediated autophagy and mitophagy (By similarity). {ECO:0000250|UniProtKB:F1LTR1, ECO:0000269|PubMed:15378603, ECO:0000269|PubMed:19446606, ECO:0000269|PubMed:23625927, ECO:0000269|PubMed:26895380, ECO:0000269|PubMed:27098453, ECO:0000269|PubMed:29911972}.
• Disease: DISEASE: Skraban-Deardorff syndrome (SKDEAS) [MIM:617616]: An autosomal dominant syndrome characterized by psychomotor developmental delay, intellectual disability with delayed speech, febrile and non-febrile seizures, abnormal gait, and facial dysmorphism. Facial features include a prominent maxilla and upper lip that readily reveal the upper gingiva, widely spaced teeth, and a broad nasal tip. {ECO:0000269|PubMed:28686853}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.156

Intolerance Scores

• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.04

Haploinsufficiency Scores

• pHI: 0.946
• hipred: Y
• hipred_score: 0.673
• ghis: 0.614

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.662

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr26

Gene ontology

• Cellular component: ubiquitin ligase complex;nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol
• Molecular function: protein binding