WDR81

WD repeat domain 81, the group of WD repeat domain containing|BEACH domain containing |Protein phosphatase 1 regulatory subunits|Armadillo like helical domain containing

Basic information

Region (hg38): 17:1716522-1738599

Links

ENSG00000167716 ∙ NCBI:124997 ∙ OMIM:614218 ∙ HGNC:26600 ∙ Uniprot:Q562E7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 (Limited), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 (Strong), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium (Supportive), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar ataxia, impaired intellectual development, and dysquilibrium syndrome 2; Hydrocephalus, nonsyndromic, autosomal recessive 3	AR	General	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	Neurologic	16371500; 21885617; 25558065; 26437881; 28556411

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR81 gene.

• not provided (204 variants)
• Inborn genetic diseases (117 variants)
• Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 (36 variants)
• not specified (19 variants)
• Hydrocephalus, congenital, 3, with brain anomalies (18 variants)
• Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2;Hydrocephalus, congenital, 3, with brain anomalies (5 variants)
• Hydrocephalus, congenital, 3, with brain anomalies;Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 (4 variants)
• WDR81-related neurodevelopmental disorder (2 variants)
• Neonatal death;Hydranencephaly;Severe brain malformation;Severe cerebellar hypoplasia (1 variants)
• Exstrophy-epispadias complex (1 variants)
• Intellectual disability (1 variants)
• WDR81-Related Disorder (1 variants)
• Microlissencephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR81 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			3	78	20	101
missense		3	173	14	1	191
nonsense	3	7	1			11
start loss						0
frameshift	4	2	1			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region		1	2	6	1	10
non coding	1		2	2	3	8
Total	8	13	181	94	24

Highest pathogenic variant AF is 0.0000328

Variants in WDR81

This is a list of pathogenic ClinVar variants found in the WDR81 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-1716626-C-T			Likely benign (Feb 01, 2024)
17-1724976-G-C		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
17-1724990-G-A		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
17-1725010-G-A			Likely benign (Jun 01, 2023)
17-1725027-C-A		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
17-1725037-C-G		Inborn genetic diseases	Uncertain significance (Mar 27, 2023)
17-1725084-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
17-1725100-G-C			Likely benign (May 20, 2018)
17-1725110-G-A		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
17-1725165-G-T		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
17-1725168-G-A		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
17-1725176-CT-C			Pathogenic (Feb 09, 2022)
17-1725204-T-C		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
17-1725229-C-T			Benign (Dec 31, 2019)
17-1725254-C-T		Inborn genetic diseases	Uncertain significance (Jul 30, 2023)
17-1725287-C-T			Likely benign (Aug 28, 2017)
17-1725291-G-C		Inborn genetic diseases	Uncertain significance (Nov 15, 2023)
17-1725296-C-T		Inborn genetic diseases	Uncertain significance (Sep 23, 2023)
17-1725300-G-C		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
17-1725341-G-C		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
17-1725418-T-A		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
17-1725435-G-A		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
17-1725441-C-T		Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2	Uncertain significance (Jan 01, 2019)
17-1725442-G-A			Likely benign (Apr 01, 2024)
17-1725446-A-G		Hydrocephalus, congenital, 3, with brain anomalies	Uncertain significance (Sep 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDR81	protein_coding	protein_coding	ENST00000409644	10	22077

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.75e-8	1.00	125557	0	47	125604	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.11	1000	1.21e+3	0.829	0.0000799	12394
Missense in Polyphen		391	528.73	0.7395		5658
Synonymous	1.60	502	550	0.913	0.0000389	4227
Loss of Function	4.57	24	63.2	0.380	0.00000336	664

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000723	0.000709
Ashkenazi Jewish	0.000102	0.0000993
East Asian	0.000164	0.000163
Finnish	0.000504	0.000462
European (Non-Finnish)	0.000162	0.000159
Middle Eastern	0.000164	0.000163
South Asian	0.0000657	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. In this process, may regulate the interaction of SQSTM1 with ubiquitinated proteins and also recruit MAP1LC3C (PubMed:28404643). May also be involved in maintenance of normal mitochondrial structure and organization (By similarity). {ECO:0000250|UniProtKB:Q5ND34, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989, ECO:0000269|PubMed:28404643}.

Intolerance Scores

• loftool: 0.504
• rvis_EVS: -1.76
• rvis_percentile_EVS: 2.34

Haploinsufficiency Scores

• pHI: 0.266
• hipred: Y
• hipred_score: 0.563
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr81
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;mitochondrion organization;negative regulation of phosphatase activity;aggrephagy;regulation of phosphatidylinositol 3-kinase activity;early endosome to late endosome transport;protein stabilization
• Cellular component: autophagosome membrane;mitochondrion;lysosomal membrane;endoplasmic reticulum membrane;Golgi apparatus;cytosol;extrinsic component of endosome membrane;early endosome membrane;late endosome membrane
• Molecular function: protein binding;phosphatidylinositol 3-kinase regulator activity;K63-linked polyubiquitin modification-dependent protein binding