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 (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.

• Skraban-Deardorff syndrome (13 variants)
• not provided (11 variants)
• Inborn genetic diseases (6 variants)
• WDR26-related disorder (1 variants)
• Intellectual disability (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.

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				6	4	10
missense		10	93	8		111
nonsense	7	1				8
start loss						0
frameshift	21	1	1			23
inframe indel		1	5	4	2	12
splice donor/acceptor (+/-2bp)	4	1				5
splice region			4	1		5
non coding			2	1	2	5
Total	32	14	101	19	8

Variants in WDR26

This is a list of pathogenic ClinVar variants found in the WDR26 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-224389854-C-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2017)
1-224393839-T-C		not specified	Uncertain significance (Jan 05, 2023)
1-224393839-TGGT-AACATTATACAAA		WDR26-related disorder	Uncertain significance (Jul 26, 2023)
1-224393853-A-G		WDR26-related disorder	Likely benign (Apr 01, 2019)
1-224393863-C-A			Uncertain significance (Dec 18, 2023)
1-224393884-T-C		Skraban-Deardorff syndrome	Pathogenic/Likely pathogenic (Jan 06, 2023)
1-224393906-T-C		not specified	Uncertain significance (Oct 22, 2018)
1-224393949-T-C		not specified	Likely benign (Jun 07, 2024)
1-224393959-G-A		WDR26-related disorder	Uncertain significance (Aug 03, 2023)
1-224393979-T-C			Benign (Dec 31, 2019)
1-224393994-C-T		Inborn genetic diseases	Pathogenic (Nov 19, 2018)
1-224398108-C-T		not specified	Uncertain significance (Sep 12, 2023)
1-224398112-C-T		Inborn genetic diseases	Likely benign (Jan 08, 2022)
1-224398124-C-T		not specified	Uncertain significance (Mar 01, 2024)
1-224398141-C-A			Uncertain significance (Jun 03, 2024)
1-224398145-A-C			Uncertain significance (Sep 06, 2022)
1-224398195-ACT-A		Skraban-Deardorff syndrome	Pathogenic (Aug 05, 2024)
1-224398208-A-C			Uncertain significance (Oct 01, 2020)
1-224398228-T-C			Pathogenic (Sep 01, 2024)
1-224398256-A-C		Skraban-Deardorff syndrome	Benign (Dec 05, 2021)
1-224398514-C-G		Intellectual disability	Pathogenic (Sep 10, 2020)
1-224398524-TACATTTAACA-T		Inborn genetic diseases	Pathogenic (Sep 22, 2017)
1-224398543-C-A			Uncertain significance (Jan 01, 2023)
1-224398543-C-T		Skraban-Deardorff syndrome	Uncertain significance (Sep 13, 2019)
1-224398548-A-AT			Pathogenic (Oct 23, 2020)

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