WBP4

protein-coding

WW domain binding protein 4, the group of Spliceosomal B complex

Gene summary

This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007187.5

Inheritance

ClinVar variants

P:6U:65B:6

Top phenotype

Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr13:41,061,509-41,084,006

External References & Databases

Ensembl (ENSG00000120688)

Transcript & Mutation Effects

hg38 • Region Span ~22.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalitiesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0971043

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalitiesAR

Manifestation: Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: Among other features, the condition can include congenital cardiac anomalies, and awareness may enable early identification and management

Refs: 37963460

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WBP4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 9

Neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalitiesTotal: 5

Neurodevelopmental disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007187.5. 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	3 clinvar	1 clinvar	6
missense			54 clinvar	2 clinvar		56
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar	3 clinvar	2 clinvar			6
splice donor/acceptor (+/-2bp)		1 clinvar	7 clinvar			8
Total	1	5	65	5	1	77

Highest pathogenic variant AF is 0.00001735868

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007187.5	RefSeq	NP_009118.1	10	MANE Select
ENST00000379487.5	Ensembl	ENSP00000368801.3	10	MANE Select
ENST00000916033.1	Ensembl	ENSP00000586092.1	10	Standard
ENST00000916033.2	Ensembl	ENSP00000586092.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

mRNA splicing, via spliceosome
mRNA cis splicing, via spliceosome

Molecular Function

nucleic acid binding
protein binding
zinc ion binding
proline-rich region binding

Cellular Component

nucleus
nucleoplasm
nuclear speck
U2-type precatalytic spliceosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379487
Coding exons: 10
Length: 22728
Individuals with no LoFs: 125682
Homozygous LoFs: 0
Heterozygous LoFs: 61
Defined: 125743
p: 0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.237	171	180	0.950	0.00000805	2458
Missense (PolyPhen)		44	50.332	0.8742		706
Synonymous	-0.470	68	63.3	1.08	0.00000308	639
Loss of Function	1.50	15	22.7	0.661	9.54e-7	322

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.0021	0.0021	notable
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00029	0.00026	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in pre-mRNA splicing as a component of the spliceosome (PubMed:9724750, PubMed:19592703, PubMed:28781166). May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex (PubMed:9724750). {ECO:0000269|PubMed:19592703, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:9724750}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.397
RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.796

Gene Damage Prediction

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