WDR33

protein-coding

WD repeat domain 33, the group of Cleavage and polyadenylation specific factor subunits|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 highly expressed in testis and the protein is localized to the nucleus. This gene may play important roles in the mechanisms of cytodifferentiation and/or DNA recombination. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_018383.5

Inheritance

—

ClinVar variants

U:144B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr2:127,701,027-127,811,187

External References & Databases

Ensembl (ENSG00000136709)

Transcript & Mutation Effects

hg38 • Region Span ~110.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDR33 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 136

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018383.5. 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			2 clinvar			2
missense			137 clinvar	2 clinvar		139
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	144	2	0	146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018383.5	RefSeq	NP_060853.3	21	MANE Select
ENST00000322313.9	Ensembl	ENSP00000325377.3	21	MANE Select
NM_001006622.3	RefSeq	NP_001006623.1	5	Standard
NM_001006623.4	RefSeq	NP_001006624.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wdr33	Danio rerio	Structure: head Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

wdr33

Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA surveillance pathway - Homo sapiens (human)
Gene expression (Transcription)
RNA Polymerase II Transcription
Metabolism of RNA
Processing of Intronless Pre-mRNAs

Biological Process

mRNA splicing, via spliceosome
postreplication repair
termination of RNA polymerase II transcription
mRNA polyadenylation
mRNA export from nucleus

Molecular Function

RNA binding

Cellular Component

fibrillar center
collagen trimer
nucleus
nucleoplasm
mRNA cleavage and polyadenylation specificity factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322313
Coding exons: 21
Length: 110166
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.90	485	795	0.610	0.0000452	8715
Missense (PolyPhen)		55	86.799	0.63365		804
Synonymous	1.14	243	267	0.911	0.0000152	2666
Loss of Function	7.23	10	79.6	0.126	0.00000532	717

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.00013	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential for both cleavage and polyadenylation of pre- mRNA 3' ends. {ECO:0000269|PubMed:19217410}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.0832
RVIS EVS: -0.81
RVIS percentile EVS: 12.05

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.798

Gene Damage Prediction

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