WBP11

protein-coding

WW domain binding protein 11, the group of Spliceosomal B complex|Protein phosphatase 1 regulatory subunits|Cilia and flagella associated

Gene summary

This gene encodes a nuclear protein, which colocalizes with mRNA splicing factors and intermediate filament-containing perinuclear networks. This protein has 95% amino acid sequence identity to the mouse Wbp11 protein. It contains two proline-rich regions that bind to the WW domain of Npw38, a nuclear protein, and thus this protein is also called Npw38-binding protein NpwBP. The Npw38-NpwBP complex may function as a component of an mRNA factory in the nucleus. [provided by RefSeq, Jul 2008]

MANE transcript

NM_016312.3

Inheritance

ClinVar variants

P:25U:125B:8

Top phenotype

Vertebral, cardiac, tracheoesophageal, renal, and limb defects

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr12:14,784,582-14,803,486

External References & Databases

Ensembl (ENSG00000084463)

Transcript & Mutation Effects

hg38 • Region Span ~18.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

vertebral, cardiac, tracheoesophageal, renal, and limb defectsSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030987

Submitter: PanelApp Australia

vertebral, cardiac, tracheoesophageal, renal, and limb defectsSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030987

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Vertebral, cardiac, tracheoesophageal, renal, and limb defectsAD

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Pulmonary; Neurologic; Renal

Intervention: Audiologic/Otolaryngologic; Cardiovascular

Rationale: Individuals have been described with hearing impairment, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with congenital cardiac anomalies, some of which required intervention, and awareness may allow surveillance and early management

Refs: 33276377

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WBP11 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 81

not providedTotal: 43

Vertebral, cardiac, tracheoesophageal, renal, and limb defectsTotal: 29

not specifiedTotal: 11

WBP11 spliceosomopathyTotal: 6

WBP11-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016312.3. 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
missense		2 clinvar	115 clinvar	6 clinvar		123
nonsense	5 clinvar	4 clinvar	1 clinvar			10
start loss						0
frameshift	6 clinvar	4 clinvar	4 clinvar			14
splice donor/acceptor (+/-2bp)		4 clinvar	5 clinvar			9
Total	11	14	125	8	0	158

Highest pathogenic variant AF is 0.0000024823535

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016312.3	RefSeq	NP_057396.1	11	MANE Select
ENST00000261167.7	Ensembl	ENSP00000261167.2	11	MANE Select
ENST00000535328.1	Ensembl	ENSP00000440988.1	3	Standard
ENST00000535638.5	Ensembl	ENSP00000443420.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

mRNA splicing, via spliceosome
rRNA processing
mRNA cis splicing, via spliceosome

Molecular Function

single-stranded DNA binding
RNA binding
protein binding
WW domain binding

Cellular Component

nucleus
nucleoplasm
cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261167
Coding exons: 11
Length: 17065
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125716
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.98	205	365	0.561	0.0000201	4132
Missense (PolyPhen)		12	31.723	0.37827		410
Synonymous	1.43	100	120	0.834	0.00000567	1329
Loss of Function	5.09	1	32.1	0.0311	0.00000226	332

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000058	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000098	0.0000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates pre-mRNA splicing. May inhibit PP1 phosphatase activity. {ECO:0000269|PubMed:10593949, ECO:0000269|PubMed:11375989, ECO:0000269|PubMed:14640981}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.0185
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.486

Gene Damage Prediction

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