WDR83

protein-coding

WD repeat domain 83, the group of Spliceosomal P complex|WD repeat domain containing|Spliceosomal C complex

Gene summary

This gene encodes a member of the WD-40 protein family. The protein is proposed to function as a molecular scaffold for various multimeric protein complexes. The protein associates with several components of the extracellular signal-regulated kinase (ERK) pathway, and promotes ERK activity in response to serum or other signals. The protein also interacts with egl nine homolog 3 (EGLN3, also known as PHD3) and regulates expression of hypoxia-inducible factor 1, and has been purified as part of the spliceosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

MANE transcript

NM_001099737.3

Inheritance

—

ClinVar variants

U:57B:4

Top phenotype

Hypercholanemia, familial

gnomAD constraint

pLI —, LoF o/e 1.02

Max pathogenic AF

—

Genomic locus

chr19:12,666,802-12,675,832

External References & Databases

Ensembl (ENSG00000123154)

Transcript & Mutation Effects

hg38 • Region Span ~9.0 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 WDR83 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 18

Hypercholanemia, familialTotal: 4

WDR83OS-related conditionTotal: 3

Neurodevelopmental disorder with variable familial hypercholanemiaTotal: 2

Attention deficit hyperactivity disorderTotal: 1

Neurodevelopmental disorder with seizures and speech and walking impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001099737.3. 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 clinvar		4
missense			54 clinvar	2 clinvar		56
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	57	4	0	61

Highest pathogenic variant AF is 0.0000041044386

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001099737.3	RefSeq	NP_001093207.1	9	MANE Select
ENST00000418543.8	Ensembl	ENSP00000402653.3	9	MANE Select
NM_032332.4	RefSeq	NP_115708.1	9	Standard
ENST00000425834.7	Ensembl	ENSP00000396530.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-Ncore
MAP2K and MAPK activation
Signal Transduction
RAF/MAP kinase cascade
MAPK1/MAPK3 signaling

Biological Process

MAPK cascade
RNA splicing, via transesterification reactions
mRNA splicing, via spliceosome

Molecular Function

protein binding

Cellular Component

spliceosomal complex
endosome membrane
catalytic step 2 spliceosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000418543
Coding exons: 9
Length: 9033
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125748
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0978	189	193	0.980	0.0000111	1995
Missense (PolyPhen)		67	69.592	0.96275		736
Synonymous	0.457	80	85.4	0.937	0.00000476	648
Loss of Function	-0.0843	17	16.6	1.02	7.16e-7	185

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00052	0.00052	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Molecular scaffold protein for various multimeric protein complexes. Acts as a module in the assembly of a multicomponent scaffold for the ERK pathway, linking ERK responses to specific agonists. At low concentrations it enhances ERK activation, whereas high concentrations lead to the inhibition of ERK activation. Also involved in response to hypoxia by acting as a negative regulator of HIF1A/HIF-1-alpha via its interaction with EGLN3/PHD3. May promote degradation of HIF1A. May act by recruiting signaling complexes to a specific upstream activator (By similarity). May also be involved in pre-mRNA splicing. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.444
RVIS EVS: -0.29
RVIS percentile EVS: 33.2

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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