ESRP2

protein-coding

epithelial splicing regulatory protein 2, the group of MicroRNA protein coding host genes|RNA binding motif containing

Gene summary

ESPR2 is an epithelial cell-type-specific splicing regulator (Warzecha et al., 2009 [PubMed 19285943]).[supplied by OMIM, Aug 2009]

Previous symbols:

RBM35B

MANE transcript

NM_024939.3

Inheritance

ClinVar variants

P:2U:121B:15

Top phenotype

ESRP2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr16:68,229,033-68,238,102

External References & Databases

Ensembl (ENSG00000103067)

Transcript & Mutation Effects

hg38 • Region Span ~9.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

orofacial cleftMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0000358

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ESRP2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 113

ESRP2-related disorderTotal: 23

Cleft lip with or without cleft palateTotal: 5

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024939.3. 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			1 clinvar	7 clinvar	4 clinvar	12
missense		1 clinvar	116 clinvar	2 clinvar	2 clinvar	121
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	2	121	9	6	138

Highest pathogenic variant AF is 0.000013011072

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024939.3	RefSeq	NP_079215.2	15	MANE Select
ENST00000473183.7	Ensembl	ENSP00000418748.2	15	MANE Select
NM_001365264.1	RefSeq	NP_001352193.1	15	Standard
NM_001365265.1	RefSeq	NP_001352194.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

FGFR2 alternative splicing
Signaling by FGFR2
Signal Transduction
Signaling by FGFR
Signaling by Receptor Tyrosine Kinases

Biological Process

alternative mRNA splicing, via spliceosome
fibroblast growth factor receptor signaling pathway
regulation of RNA splicing
positive regulation of epithelial cell proliferation
epithelial tube branching involved in lung morphogenesis

Molecular Function

RNA binding
mRNA binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000473183
Coding exons: 15
Length: 8992
Individuals with no LoFs: 125680
Homozygous LoFs: 0
Heterozygous LoFs: 68
Defined: 125748
p: 0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.824	400	449	0.891	0.0000278	4535
Missense (PolyPhen)		167	196.07	0.85175		2034
Synonymous	1.37	166	190	0.874	0.0000118	1593
Loss of Function	2.90	17	35.7	0.476	0.00000204	363

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00083	0.00079	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.000079	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Also regulates the splicing of CD44, CTNND1, ENAH, 3 transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of FGFR2. {ECO:0000269|PubMed:19285943}.;

Intolerance Scores

LoFtool: 0.741
RVIS EVS: -0.73
RVIS percentile EVS: 14.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.138

Gene Damage Prediction

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