WDR11
protein-codingWD repeat domain 11, the group of WD repeat domain containing
Gene summary
This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus. [provided by RefSeq, Jul 2008]
- BRWD2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~58.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018555
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0013926
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0859373
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0013926
Submitter: Illumina
Inheritance Pattern: AR
Disease ID:MONDO:0859373
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0013926
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859373
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0018800
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0013926
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0859373
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Neurologic
Intervention: Endocrine
Rationale: In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to WDR11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018117.12. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 57 | 5 | 66 | ||
| missense | 1 | 1 | 243 | 17 | 262 | |
| nonsense | 3 | 5 | 4 | 12 | ||
| start loss | 0 | |||||
| frameshift | 2 | 5 | 3 | 10 | ||
| splice donor/acceptor (+/-2bp) | 1 | 4 | 3 | 8 | ||
| Total | 7 | 15 | 257 | 74 | 5 | 358 |
Highest pathogenic variant AF is 0.00007868864
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060587.8 | 29 | MANE Select | |
| Ensembl | ENSP00000263461.5 | 29 | MANE Select | |
| Ensembl | ENSP00000474595.1 | 5 | Standard | |
| Ensembl | ENSP00000474880.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in leukocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
Biological Process
- intracellular protein transport
- heart development
- regulation of smoothened signaling pathway
- multicellular organism growth
- cilium assembly
Molecular Function
- protein binding
Cellular Component
- nucleus
- cytoplasm
- lysosomal membrane
- trans-Golgi network
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263461
- Coding exons
- 29
- Length
- 58350
- Individuals with no LoFs
- 125678
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 70
- Defined
- 125748
- p
- 0.000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.80 | 528 | 658 | 0.803 | 0.0000359 | 7980 |
| Missense (PolyPhen) | 91 | 130.88 | 0.69529 | 1513 | ||
| Synonymous | 1.17 | 219 | 242 | 0.904 | 0.0000133 | 2359 |
| Loss of Function | 4.70 | 26 | 67.8 | 0.384 | 0.00000344 | 830 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00072 | 0.00072 | rare |
| Ashkenazi Jewish | 0.00031 | 0.00030 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00049 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis (PubMed:29263200). Regulates the proteolytic processing of GLI3 and cooperates with the transcription factor EMX1 in the induction of downstream Hh pathway gene expression and gonadotropin-releasing hormone production (PubMed:29263200). WDR11 complex facilitates the tethering of Adaptor protein-1 complex (AP-1)-derived vesicles. WDR11 complex acts together with TBC1D23 to facilitate the golgin- mediated capture of vesicles generated using AP-1 (PubMed:29426865). {ECO:0000269|PubMed:29263200, ECO:0000269|PubMed:29426865}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving WDR11 is found in a form of Kallmann syndrome. Translocation 46,XY,t(10;12)(q26.12;q13.11). {ECO:0000269|PubMed:20887964}.; DISEASE: Hypogonadotropic hypogonadism 14 with or without anosmia (HH14) [MIM:614858]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:20887964, ECO:0000269|PubMed:29263200}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.143
Intolerance Scores
- LoFtool
- 0.111
- RVIS EVS
- -0.93
- RVIS percentile EVS
- 9.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |