WDR4

WD repeat domain 4, the group of WD repeat domain containing

Basic information

Region (hg38): 21:42843094-42879568

Links

ENSG00000160193 ∙ NCBI:10785 ∙ OMIM:605924 ∙ HGNC:12756 ∙ Uniprot:P57081 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Galloway-Mowat syndrome 6 (Limited), mode of inheritance: AR
• Galloway-Mowat syndrome (Supportive), mode of inheritance: AR
• microcephaly, growth deficiency, seizures, and brain malformations (Moderate), mode of inheritance: AR
• microcephaly, growth deficiency, seizures, and brain malformations (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galloway-Mowat syndrome 6	AR	Endocrine; Renal	Endocrine manifestations such as growth hormone deficiency have been observed, and awareness may allow prompt recognition and treatment; Among other features, the condition may include renal disease, and use of immunosuppressive treatments has been described as necessary in at least one patient	Craniofacial; Endocrine; Neurologic; Renal	26416026; 28617965; 29597095; 30079490

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR4 gene.

• not_provided (199 variants)
• Inborn_genetic_diseases (107 variants)
• WDR4-related_disorder (28 variants)
• Galloway-Mowat_syndrome_6 (14 variants)
• Microcephaly,_growth_deficiency,_seizures,_and_brain_malformations (8 variants)
• not_specified (3 variants)
• Galloway-Mowat_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018669.6. 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				64	5	69
missense	1	4	118	18		141
nonsense	3					3
start loss		1	1			2
frameshift	4		1			5
splice donor/acceptor (+/-2bp)		4	1			5
Total	8	9	121	82	5

Highest pathogenic variant AF is 0.0000136395

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDR4	protein_coding	protein_coding	ENST00000398208	11	36475

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.38e-8	0.595	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.02	304	258	1.18	0.0000165	2636
Missense in Polyphen		64	60.167	1.0637		695
Synonymous	-1.47	134	114	1.18	0.00000807	808
Loss of Function	1.16	15	20.7	0.725	9.73e-7	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000263	0.000243
Ashkenazi Jewish	0.000399	0.000397
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000108	0.0000967
Middle Eastern	0.000218	0.000217
South Asian	0.000171	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. In the complex, it is required to stabilize and induce conformational changes of the catalytic subunit. {ECO:0000255|HAMAP-Rule:MF_03056, ECO:0000269|PubMed:12403464}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.820
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.72

Haploinsufficiency Scores

• pHI: 0.840
• hipred: N
• hipred_score: 0.200
• ghis: 0.614

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.939

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr4
• Phenotype: 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); 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); embryo 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); cellular phenotype

Gene ontology

• Biological process: tRNA modification;tRNA (guanine-N7)-methylation
• Cellular component: nucleus;nucleoplasm;cytosol;tRNA methyltransferase complex
• Molecular function: protein binding;tRNA (guanine-N7-)-methyltransferase activity