WDR11

WD repeat domain 11, the group of WD repeat domain containing

Basic information

Region (hg38): 10:120851305-120909524

Previous symbols: [ "BRWD2" ]

Links

ENSG00000120008 ∙ NCBI:55717 ∙ OMIM:606417 ∙ HGNC:13831 ∙ Uniprot:Q9BZH6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Kallmann syndrome (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 14 with or without anosmia (Moderate), mode of inheritance: AD
• hypogonadotropic hypogonadism 14 with or without anosmia (Strong), mode of inheritance: AD
• hypogonadotropic hypogonadism 14 with or without anosmia (Limited), mode of inheritance: AD
• intellectual developmental disorder, autosomal recessive 78 (Limited), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 78 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 14 with or without anosmia	AD	Endocrine	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	Endocrine; Neurologic	20887964

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR11 gene.

• Intellectual developmental disorder, autosomal recessive 78 (4 variants)
• Microcephaly (4 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR11 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			1	37	12	50
missense			104	7		111
nonsense	2	1	2			5
start loss						0
frameshift	3	1	2			6
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region			2	4	2	8
non coding			6	56	113	175
Total	6	4	115	100	125

Highest pathogenic variant AF is 0.0000263

Variants in WDR11

This is a list of pathogenic ClinVar variants found in the WDR11 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-120851415-G-A			Benign (Nov 15, 2018)
10-120851418-G-A			Benign (Oct 12, 2020)
10-120851426-G-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 16, 2023)
10-120851427-C-T		Inborn genetic diseases	Uncertain significance (Oct 07, 2021)
10-120851428-C-G			Uncertain significance (Sep 20, 2022)
10-120851428-C-T		WDR11-related disorder	Uncertain significance (Oct 27, 2022)
10-120851436-G-A		Amenorrhea	Uncertain significance (Mar 08, 2021)
10-120851453-G-C			Likely benign (Apr 22, 2022)
10-120851471-G-T			Benign (Jan 29, 2024)
10-120851479-A-G			Uncertain significance (Nov 03, 2023)
10-120851485-A-C			Uncertain significance (Dec 26, 2023)
10-120851496-G-A		not specified	Uncertain significance (Aug 23, 2019)
10-120851514-C-T			Likely benign (Nov 22, 2023)
10-120851534-A-G			Likely benign (Nov 27, 2018)
10-120851649-T-C			Likely benign (May 20, 2019)
10-120852260-A-T			Benign (Aug 30, 2018)
10-120852546-T-C			Uncertain significance (Oct 22, 2022)
10-120852599-T-TC		Hypogonadotropic hypogonadism 14 with or without anosmia	Likely pathogenic (May 22, 2022)
10-120852609-G-A			Uncertain significance (Jun 30, 2023)
10-120852958-G-A			Benign (Sep 05, 2018)
10-120858636-G-C		Hypogonadotropic hypogonadism 14 with or without anosmia	Benign (Jan 29, 2024)
10-120858673-A-G			Uncertain significance (Aug 24, 2022)
10-120858698-G-C		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
10-120858732-C-T		WDR11-related disorder	Likely benign (Jan 13, 2024)
10-120858733-G-A			Uncertain significance (Sep 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDR11	protein_coding	protein_coding	ENST00000263461	29	58350

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.37e-8	1.00	125678	0	70	125748	0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.80	528	658	0.803	0.0000359	7980
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00110	0.00109
Ashkenazi Jewish	0.000306	0.000298
East Asian	0.000382	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.000382	0.000381
South Asian	0.000261	0.000261
Other	0.000491	0.000326

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.111
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.75

Haploinsufficiency Scores

• pHI: 0.178
• hipred: N
• hipred_score: 0.476
• ghis: 0.663

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr11
• Phenotype: cellular phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); taste/olfaction phenotype; growth/size/body region phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; vision/eye phenotype; limbs/digits/tail 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); digestive/alimentary phenotype; reproductive system phenotype; 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); 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); liver/biliary system phenotype; respiratory system phenotype

Gene ontology

• Biological process: intracellular protein transport;heart development;regulation of smoothened signaling pathway;multicellular organism growth;cilium assembly;head development;vesicle tethering to Golgi
• Cellular component: nucleus;cytoplasm;lysosomal membrane;trans-Golgi network;cytosol;axoneme;microtubule cytoskeleton;membrane;cytoplasmic vesicle;ciliary basal body
• Molecular function: protein binding