ESRP1

epithelial splicing regulatory protein 1, the group of RNA binding motif containing

Basic information

Region (hg38): 8:94641073-94707466

Previous symbols: [ "RBM35A" ]

Links

ENSG00000104413 ∙ NCBI:54845 ∙ OMIM:612959 ∙ HGNC:25966 ∙ Uniprot:Q6NXG1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive 109 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive 109 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 109	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	29107558

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ESRP1 gene.

• Inborn genetic diseases (20 variants)
• not provided (7 variants)
• Hearing loss, autosomal recessive 109 (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ESRP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	4	6
missense	1		20	1		22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					4	4
Total	1	0	20	3	8

Variants in ESRP1

This is a list of pathogenic ClinVar variants found in the ESRP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-94641946-A-G		ESRP1-related disorder	Benign/Likely benign (Feb 28, 2019)
8-94641953-G-C		ESRP1-related disorder	Likely benign (Mar 09, 2021)
8-94641975-T-C		not specified	Uncertain significance (Feb 16, 2023)
8-94641978-T-C		not specified	Uncertain significance (May 13, 2022)
8-94641998-G-C		not specified	Uncertain significance (Apr 08, 2022)
8-94643327-C-A		not specified	Uncertain significance (Oct 20, 2021)
8-94643344-G-A		ESRP1-related disorder	Likely benign (Apr 29, 2019)
8-94643368-T-C		ESRP1-related disorder	Benign (Oct 30, 2019)
8-94646179-A-G		ESRP1-related disorder	Benign (Dec 31, 2019)
8-94646201-T-A		not specified	Uncertain significance (Feb 28, 2024)
8-94646211-G-A		not specified	Uncertain significance (Sep 30, 2021)
8-94646229-G-A		not specified	Uncertain significance (Feb 03, 2022)
8-94646263-C-A		not specified	Uncertain significance (Mar 23, 2023)
8-94646267-G-A			Likely benign (Oct 29, 2018)
8-94646275-G-T		not specified	Uncertain significance (Dec 12, 2023)
8-94646277-C-G		not specified	Uncertain significance (Oct 06, 2021)
8-94646298-T-C		Hearing loss, autosomal recessive 109	Benign (Jul 30, 2021)
8-94662290-G-A		not specified	Likely benign (Nov 27, 2023)
8-94662302-C-G		not specified	Uncertain significance (Aug 13, 2021)
8-94662327-A-C		not specified	Uncertain significance (Feb 23, 2023)
8-94662380-G-T			Benign (Dec 24, 2018)
8-94662529-G-C		ESRP1-related disorder	Likely benign (May 20, 2019)
8-94664715-TGATGATAACACCGTAGTCA-T		Hearing loss, autosomal recessive 109	Pathogenic (Sep 21, 2018)
8-94664728-G-A		not specified	Uncertain significance (Jul 26, 2022)
8-94664749-C-T		not specified	Uncertain significance (Jun 21, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ESRP1	protein_coding	protein_coding	ENST00000433389	15	66393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000661	124629	0	10	124639	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	245	367	0.667	0.0000184	4424
Missense in Polyphen		58	129.53	0.44778		1473
Synonymous	0.0965	140	141	0.990	0.00000758	1351
Loss of Function	5.17	4	38.8	0.103	0.00000232	423

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000664	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.0000366	0.0000354
Middle Eastern	0.000167	0.000167
South Asian	0.0000775	0.0000654
Other	0.00	0.00

dbNSFP

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 (PubMed:19285943). Regulates splicing and expression of genes involved in inner ear development, auditory hair cell differentiation, and cell fate specification in the cochlear epithelium (By similarity). {ECO:0000250|UniProtKB:Q3US41, ECO:0000269|PubMed:19285943}.
• Disease: DISEASE: Deafness, autosomal recessive, 109 (DFNB109) [MIM:618013]: A form of non-syndromic, sensorineural deafness characterized by bilateral, congenital, severe to profound hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB109 affected individuals additionally exhibit vestibular dysplasia, although they do not manifest problems with balance or movement. {ECO:0000269|PubMed:29107558}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: FGFR2 alternative splicing;Signaling by FGFR2;Disease;Signal Transduction;Signaling by FGFR;Signaling by Receptor Tyrosine Kinases;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.594
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.7

Haploinsufficiency Scores

• pHI: 0.664
• hipred: Y
• hipred_score: 0.768
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.215

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Esrp1
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Gene ontology

• Biological process: mRNA processing;RNA splicing;fibroblast growth factor receptor signaling pathway;regulation of inner ear auditory receptor cell fate specification;regulation of RNA splicing
• Cellular component: nucleus;nucleoplasm;nuclear body
• Molecular function: mRNA binding;protein binding