ESRP1

Summary

ESRP1 (epithelial splicing regulatory protein 1, HGNC:25966) is a protein-coding gene on chromosome 8q22.1, encoding Epithelial splicing regulatory protein 1 (Q6NXG1). mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms.

ESPR1 is an epithelial cell-type-specific splicing regulator (Warzecha et al., 2009 [PubMed 19285943]).

Source: NCBI Gene 54845 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive 109 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 116 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes
• MANE Select transcript: NM_017697

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25966
Approved symbol	ESRP1
Name	epithelial splicing regulatory protein 1
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20171
Ensembl gene	ENSG00000104413
Ensembl biotype	protein_coding
OMIM	612959
Entrez	54845

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000358397, ENST00000423620, ENST00000433389, ENST00000454170, ENST00000517556, ENST00000517610, ENST00000519505, ENST00000520385, ENST00000522756, ENST00000522920, ENST00000523347, ENST00000646773, ENST00000853635, ENST00000853636, ENST00000853637, ENST00000853638, ENST00000918824, ENST00000918825, ENST00000918826

RefSeq mRNA: 5 — MANE Select: NM_017697 NM_001034915, NM_001122825, NM_001122826, NM_001122827, NM_017697

CCDS: CCDS47895, CCDS47896, CCDS47897, CCDS47898, CCDS87620

Canonical transcript exons

ENST00000433389 — 16 exons

Exon	Start	End
ENSE00000700122	94667949	94668250
ENSE00001290780	94662272	94662370
ENSE00001304695	94664927	94665059
ENSE00001310550	94671453	94671671
ENSE00001318199	94641956	94642084
ENSE00001325312	94665154	94665196
ENSE00001478828	94674308	94674506
ENSE00001601726	94678203	94678371
ENSE00001707750	94692677	94692827
ENSE00002117429	94641174	94641450
ENSE00003517556	94662501	94662555
ENSE00003550856	94696852	94696961
ENSE00003587667	94705925	94707466
ENSE00003599056	94643303	94643416
ENSE00003651346	94664697	94664807
ENSE00003671005	94646168	94646282

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 99.06.

FANTOM5 (CAGE): breadth broad, TPM avg 15.7262 / max 394.6969, expressed in 472 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89784	10.5122	448
89785	2.2592	388
89783	1.7715	377
89786	0.5855	253
89782	0.3000	192
89787	0.1243	78
89781	0.0703	35
89789	0.0538	27
89790	0.0346	24
89791	0.0147	7

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.06	gold quality
colonic mucosa	UBERON:0000317	98.18	gold quality
gingival epithelium	UBERON:0001949	98.16	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.16	gold quality
gingiva	UBERON:0001828	97.97	gold quality
upper leg skin	UBERON:0004262	97.79	gold quality
mucosa of transverse colon	UBERON:0004991	97.72	gold quality
lower esophagus mucosa	UBERON:0035834	97.66	gold quality
esophagus squamous epithelium	UBERON:0006920	97.17	gold quality
mammalian vulva	UBERON:0000997	97.13	gold quality
rectum	UBERON:0001052	97.02	gold quality
corpus epididymis	UBERON:0004359	96.90	gold quality
skin of abdomen	UBERON:0001416	96.66	gold quality
buccal mucosa cell	CL:0002336	96.60	gold quality
oral cavity	UBERON:0000167	96.56	gold quality
esophagus mucosa	UBERON:0002469	96.26	gold quality
epithelium of esophagus	UBERON:0001976	96.14	gold quality
body of pancreas	UBERON:0001150	95.99	gold quality
skin of leg	UBERON:0001511	95.96	gold quality
oocyte	CL:0000023	95.91	gold quality
zone of skin	UBERON:0000014	95.91	gold quality
upper arm skin	UBERON:0004263	95.56	gold quality
pharyngeal mucosa	UBERON:0000355	95.48	gold quality
palpebral conjunctiva	UBERON:0001812	95.29	gold quality
skin of hip	UBERON:0001554	95.27	gold quality
squamous epithelium	UBERON:0006914	95.24	gold quality
bronchial epithelial cell	CL:0002328	94.58	gold quality
penis	UBERON:0000989	94.21	gold quality
pancreas	UBERON:0001264	93.65	gold quality
oviduct epithelium	UBERON:0004804	93.11	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	265.07
E-ANND-3	yes	14.79
E-MTAB-9388	yes	11.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KDM5B, SNAI1, ZEB1

miRNA regulators (miRDB)

104 targeting ESRP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 40)

• The FLJ20171 gene was shown to effectively separate these two chromophobe renal cell carcinoma (RCC) and benign oncocytoma groups by quantitative reverse transcription-PCR using fresh tissue samples, with similar trends seen on formalin-fixed tissues. (PMID:17145811)
• Results demonstrate that RBM35A functions as a tumor suppressor in colon cancer cells, and suggest that RBM35A is involved in posttranscriptional regulation of a number of genes by exerting a differential effect on protein translation via 5’UTRs of mRNAs. (PMID:19177006)
• ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. (PMID:19285943)
• results further establish ESRP1 and ESRP2 as global regulators of an epithelial splicing regulatory network. (PMID:19829082)
• ESRP1 coordinates a complex alternative splicing network that adds an important post-transcriptional layer to the changes in gene expression that underlie epithelial-mesenchymal transitions during development and disease. (PMID:20711167)
• The functional significance of EMT-associated alternative splicing was tested by expression of the epithelial-specific splicing factor ESRP1 (PMID:21876675)
• deltaEF1 family proteins repress the expression of ESRPs to regulate alternative splicing during TGF-beta-induced EMT and the progression of breast cancers (PMID:22037216)
• functions of the ESRP1 in an epithelial posttranscriptional gene expression program. (PMID:22354987)
• ESRP1 could be a master regulator of the EMT process in pituitary adenomas causing acromegaly. (PMID:22585092)
• the transcription repressor Snail binds to E-boxes in the ESRP1 promoter, causing repression of the ESRP1 gene. (PMID:22961986)
• ESRP1 and PNN modulate alternative splicing of a specific subset of target genes, but not general splicing events, in HCET cells to maintain or enhance epithelial characteristics. (PMID:23299472)
• Data suggest that alternative splicing in ESRP1 transcripts in somatotroph adenomas is essential in epithelial-mesenchymal transition progression and in response to somatostatin analog antineoplastic treatment. (PMID:23825128)
• Results show that ESRP1 regulates the expression pattern of FGFR-2 isoforms, attenuates cell growth, migration, invasion and metastasis, and is a favorable prognostic factor in pancreatic ductal adenocarcinoma. (PMID:24077287)
• ESRP1 and ESRP2 suppress cancer cell motility via different mechanisms. (PMID:25143390)
• MCL1 with the deletion of 801G and 802A sites could not be correctly spliced by ESRP1 and no significant difference was seen in the expressions of isoform 1 and 3 in mutant MCL1 (PMID:26522352)
• Data show that both rab G-Protein RAB25 and RNA-binding protein ESRP1 were suppressed by transcription factor ZEB1, which was in turn regulated via epigenetic mechanisms. (PMID:26646320)
• Altered Expression and Splicing of ESRP1 in Malignant Melanoma Correlates with Epithelial-Mesenchymal Status and Tumor-Associated Immune Cytolytic Activity. (PMID:27045022)
• Recombinant human ESRP1-RRM3 was subjected to biomolecular NMR and its chemical shifts and structural coordinates were determined and deposited in the BioMagResBank and Protein Data Bank respectively. Its interaction with RBPMS2 was mapped. (PMID:27108394)
• ALK oncogenic activity is involved in the regulation of an epithelial mesenchymal transition phenotype in a subset of non-small cell lung carcinomas by repression of the epithelial splicing regulatory protein 1. (PMID:27119231)
• The molecular mechanisms by which ESRP1 and ESPR2 exert positive as well as negative effects on cancer progression have been summarized. (Review) (PMID:27401076)
• ZEB1-induced epithelial-to-mesenchymal transition and associated molecular changes in ESRP1 and CD44 contribute to early pathogenesis and metastatic potential in established lung cancer (PMID:27500490)
• Our study supports the role of ESRP1 as tumor suppressor and strongly suggests that ESRPs are candidate markers for early detection, diagnosis, and prognosis of CRC. (PMID:27650542)
• Results showed that the expression patterns of these genes were indicative of the onset of EMT in in-vitro models, but not in tissue samples. However, the ratio between ESRP1 or ESRP2 and RBFOX2 significantly decreased during EMT and positively correlated with the EMT-specific phenotype in cell models. Low ESRP1/RBFOX2 ratio value was associated with a higher risk of metastasis in early breast cancer patients. (PMID:27911856)
• High ESRP1 expression may thus stimulate growth of cancer epithelial cells and promote colorectal cancer progression. (PMID:28052020)
• In humans, ESRP1 is downregulated in inflamed biopsies from inflammatory bowel disease patients. ESRP1 loss is an adverse prognostic factor in colorectal cancer. Furthermore, generation of ESRP1-dependent GPR137 isoforms is altered in colorectal cancer and expression of a specific GPR137 isoform predicts colorectal cancer patient survival. (PMID:28975893)
• Results show that ESRP1 regulates CD44 splice isoform switching and EMT in ovarian cancer cells. (PMID:29130517)
• Downregulated ESRP1 by sirna resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition. (PMID:29131012)
• study defines a Snail-ESRP1 cancer axis that is crucial for human lung carcinogenesis, with implications for new intervention strategies and translational opportunities (PMID:29431637)
• Low ESRP1 expression is associated with Invasion and Metastasis of Lung Adenocarcinoma. (PMID:29803834)
• effect of ESRP1 and CD44 on human PSC pluripotency is isoform-dependent and that ESRP1-induced CD44 v3 is functionally associated with human PSC pluripotency control (PMID:29873154)
• we have demonstrated that ESRP1 overexpression induces G1-phase cell cycle arrest via reducing the stability of the cyclin A2 mRNA. (PMID:31362365)
• Splicing factor derived circular RNA circUHRF1 accelerates oral squamous cell carcinoma tumorigenesis via feedback loop. (PMID:31570856)
• Proteomics-Based Evidence for a Pro-Oncogenic Role of ESRP1 in Human Colorectal Cancer Cells. (PMID:31963158)
• Expression of ESRP1 at human fetomaternal interface and involvement in trophoblast migration and invasion. (PMID:32056547)
• Emerging Multi-cancer Regulatory Role of ESRP1: Orchestration of Alternative Splicing to Control EMT. (PMID:32564755)
• ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression. (PMID:32641707)
• Mining Database for the Clinical Significance and Prognostic Value of ESRP1 in Cutaneous Malignant Melanoma. (PMID:32964032)
• APC regulation of ESRP1 and p120-catenin isoforms in colorectal cancer cells. (PMID:33237836)
• Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer. (PMID:33339518)
• Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer. (PMID:33455017)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	esrp1	ENSDARG00000011245
mus_musculus	Esrp1	ENSMUSG00000040728
rattus_norvegicus	Esrp1	ENSRNOG00000008184
drosophila_melanogaster	fus	FBGN0023441
drosophila_melanogaster	glo	FBGN0259139
caenorhabditis_elegans		WBGENE00006367
caenorhabditis_elegans	rbm-12	WBGENE00013703
caenorhabditis_elegans		WBGENE00022253

Paralogs (8): HNRNPH3 (ENSG00000096746), ESRP2 (ENSG00000103067), HNRNPH2 (ENSG00000126945), GRSF1 (ENSG00000132463), HNRNPH1 (ENSG00000169045), HNRNPF (ENSG00000169813), RBM12B (ENSG00000183808), RBM12 (ENSG00000244462)

Protein

Protein identifiers

Epithelial splicing regulatory protein 1 — Q6NXG1 (reviewed: Q6NXG1)

Alternative names: RNA-binding motif protein 35A, RNA-binding protein 35A

All UniProt accessions (5): Q6NXG1, A0A2U3TZN9, E5RI26, H0YBB3, H0YBR2

UniProt curated annotations — full annotation on UniProt →

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. Regulates splicing and expression of genes involved in inner ear development, auditory hair cell differentiation, and cell fate specification in the cochlear epithelium.

Subcellular location. Nucleus.

Tissue specificity. Epithelial cell-specific.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. Down-regulated during the epithelial-to-mesenchymal transition (EMT).

Similarity. Belongs to the ESRP family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6NXG1-1	1	yes
Q6NXG1-2	2
Q6NXG1-3	3
Q6NXG1-4	4
Q6NXG1-5	5

RefSeq proteins (5): NP_001030087, NP_001116297, NP_001116298, NP_001116299, NP_060167* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034427	ESRP1_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR050666	ESRP	Family

UniProt features (67 total): helix 26, strand 21, turn 6, splice variant 4, domain 3, sequence variant 2, sequence conflict 2, modified residue 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7VKJ	X-RAY DIFFRACTION	1.45
7VKI	X-RAY DIFFRACTION	1.65
7WRN	X-RAY DIFFRACTION	1.85
2DHA	SOLUTION NMR
2RVJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NXG1-F1	78.21	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 543, 582

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6803529	FGFR2 alternative splicing

MSigDB gene sets: 179 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_EPITHELIUM_DEVELOPMENT, MODULE_451, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, REACTOME_SIGNALING_BY_FGFR, GOBP_NEUROGENESIS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EAR_DEVELOPMENT, MARTINEZ_RB1_TARGETS_DN, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GOBP_NEURON_FATE_SPECIFICATION, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP

GO Biological Process (4): mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of inner ear auditory receptor cell fate specification (GO:0042669), regulation of RNA splicing (GO:0043484)

GO Molecular Function (4): mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Oncogenic MAPK signaling	1
Signaling by FGFR2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
mRNA metabolic process	1
regulation of cell fate specification	1
auditory receptor cell fate specification	1
regulation of inner ear auditory receptor cell differentiation	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
RNA binding	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ESRP1	ENAH	Q8N8S7	906
ESRP1	CTNND1	O60716	841
ESRP1	RRM1	P23921	831
ESRP1	FGFR2	P18443	768
ESRP1	CD44	P16070	751
ESRP1	QKI	Q96PU8	719
ESRP1	HNRNPM	P52272	667
ESRP1	SRSF1	Q07955	646
ESRP1	RBFOX2	O43251	645
ESRP1	ZEB1	P37275	607
ESRP1	MBNL1	Q9NR56	600
ESRP1	PTBP1	P26599	541
ESRP1	RBM47	A0AV96	533
ESRP1	GRHL2	Q6ISB3	533
ESRP1	KHDRBS2	Q5VWX1	516

IntAct

130 interactions, top by confidence:

A	B	Type	Score
ESRP1	ATXN1	psi-mi:“MI:0915”(physical association)	0.810
ATXN1	ESRP1	psi-mi:“MI:0915”(physical association)	0.810
ESRP1	RBPMS2	psi-mi:“MI:0915”(physical association)	0.740
ESRP1	MED25	psi-mi:“MI:0915”(physical association)	0.560
PRR20D	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	KLHDC7B	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	OXER1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-5	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
DAZAP2	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	ATP1A3	psi-mi:“MI:0915”(physical association)	0.560
CHAT	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
CRYAA	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	DCTN1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	ATN1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1		psi-mi:“MI:0915”(physical association)	0.560
ESRP1	F13A1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
HSPD1	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	PECAM1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (100): ESRP1 (Two-hybrid), ESRP1 (Affinity Capture-MS), ESRP1 (Affinity Capture-MS), ESRP1 (Affinity Capture-Western), RGPD8 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RBPMS (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RBPMS2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), ZNF703 (Affinity Capture-MS), HELZ (Affinity Capture-MS), ELAVL2 (Affinity Capture-MS), GPATCH8 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2P872, A1L1C7, A4IIM2, B2RYD2, F1LQ48, O57406, O88532, O95319, P14866, P28659, P51513, P57723, P57724, Q28HE9, Q2PFW9, Q32PX7, Q3U0V1, Q3US41, Q4QQT3, Q4R535, Q58A45, Q5F3T7, Q5NVC8, Q5R8Y8, Q5R995, Q5U231, Q640Q5, Q6DGV1, Q6GPM1, Q6NXG1, Q6P0B1, Q6PF35, Q792H5, Q7T2T1, Q7TSY6, Q7ZXE2, Q80WA4, Q8R081, Q8UVD9, Q91WJ8

Diamond homologs: A1L1G1, A8WPC5, B2RYD2, B2RYJ8, O35737, P31943, P52597, P55795, P70333, Q12849, Q22708, Q3SZF3, Q3US41, Q5E9J1, Q5RD26, Q5ZLR4, Q60HC3, Q6AY09, Q6DEZ7, Q6NXG1, Q794E4, Q7ZVR8, Q7ZY29, Q8C5Q4, Q8K0G8, Q8R3C6, Q8VHV7, Q9BJZ5, Q9H6T0, Q9Z2X1, P31942, Q9Y4C8, Q15020, Q5REG1, Q9JLI8, Q66JV4, Q80YR9, Q5RFT7, Q8IXT5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

116 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	68
Likely benign	16
Benign	10

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
545505	NM_017697.4(ESRP1):c.665_683del (p.Asp222fs)	Pathogenic
545506	NM_017697.4(ESRP1):c.775C>G (p.Leu259Val)	Pathogenic
4845910	NM_017697.4(ESRP1):c.1535dup (p.Asn512fs)	Likely pathogenic

SpliceAI

3105 predictions. Top by Δscore:

Variant	Effect	Δscore
8:94641951:C:CA	acceptor_gain	1.0000
8:94641952:G:A	acceptor_gain	1.0000
8:94643301:A:AG	acceptor_gain	1.0000
8:94643302:G:GG	acceptor_gain	1.0000
8:94643414:AAG:A	donor_loss	1.0000
8:94643415:AGGTA:A	donor_loss	1.0000
8:94643416:GGTAA:G	donor_loss	1.0000
8:94643417:G:GA	donor_loss	1.0000
8:94643418:T:A	donor_loss	1.0000
8:94646167:GAAT:G	acceptor_gain	1.0000
8:94646203:T:TA	acceptor_gain	1.0000
8:94662553:TTGG:T	donor_loss	1.0000
8:94662554:TGG:T	donor_loss	1.0000
8:94662555:GGTAA:G	donor_loss	1.0000
8:94662556:G:GG	donor_gain	1.0000
8:94662556:GT:G	donor_loss	1.0000
8:94662557:T:TC	donor_loss	1.0000
8:94664808:G:GG	donor_gain	1.0000
8:94665149:CTCA:C	acceptor_loss	1.0000
8:94665150:TCA:T	acceptor_loss	1.0000
8:94665151:CAG:C	acceptor_loss	1.0000
8:94665152:A:AG	acceptor_gain	1.0000
8:94665152:A:AT	acceptor_loss	1.0000
8:94665153:G:GG	acceptor_gain	1.0000
8:94665194:GTG:G	donor_gain	1.0000
8:94665197:G:A	donor_loss	1.0000
8:94665197:G:GG	donor_gain	1.0000
8:94667934:ATTT:A	acceptor_gain	1.0000
8:94667947:A:C	acceptor_loss	1.0000
8:94667948:GGT:G	acceptor_gain	1.0000

AlphaMissense

4453 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:94664743:G:C	G231R	1.000
8:94664743:G:T	G231C	1.000
8:94664744:G:A	G231D	1.000
8:94664747:T:C	L232S	1.000
8:94664752:T:A	W234R	1.000
8:94664752:T:C	W234R	1.000
8:94664754:G:C	W234C	1.000
8:94664754:G:T	W234C	1.000
8:94664782:T:C	F244L	1.000
8:94664783:T:C	F244S	1.000
8:94664784:C:A	F244L	1.000
8:94664784:C:G	F244L	1.000
8:94664791:G:A	G247R	1.000
8:94664791:G:C	G247R	1.000
8:94664947:T:C	L259P	1.000
8:94664958:G:C	G263R	1.000
8:94664959:G:A	G263D	1.000
8:94664965:G:C	R265T	1.000
8:94664965:G:T	R265M	1.000
8:94664966:G:C	R265S	1.000
8:94664966:G:T	R265S	1.000
8:94664970:G:A	G267R	1.000
8:94664970:G:C	G267R	1.000
8:94664971:G:A	G267E	1.000
8:94664971:G:T	G267V	1.000
8:94664976:G:C	A269P	1.000
8:94664977:C:A	A269D	1.000
8:94664980:T:C	L270P	1.000
8:94664983:T:A	V271D	1.000
8:94664989:T:C	F273S	1.000

dbSNP variants (sampled 300 via entrez): RS1000116262 (8:94706095 C>A,T), RS1000129294 (8:94672227 C>T), RS1000130134 (8:94664506 A>T), RS1000225417 (8:94680484 A>G), RS1000387194 (8:94678079 G>A), RS1000474675 (8:94700667 C>T), RS1000501737 (8:94677024 A>G), RS1000574374 (8:94701288 AAG>A), RS1000680122 (8:94665408 T>C), RS1000762463 (8:94647651 T>C), RS1000763939 (8:94689503 C>G), RS1000768570 (8:94700743 C>T), RS1000795234 (8:94657949 T>C), RS1000861240 (8:94683223 C>T), RS1000873183 (8:94640389 G>A)

Disease associations

OMIM: gene MIM:612959 | disease phenotypes: MIM:618013

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive 109	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Limited	AR

Mondo (1): hearing loss, autosomal recessive 109 (MONDO:0033202)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0008527	Congenital sensorineural hearing impairment
HP:0008555	Absent vestibular function
HP:0011380	Abnormal semicircular canal morphology

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008971_28	Urate levels	2.000000e-08
GCST009303_18	Abstraction and mental flexibility	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0009332	executive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295865 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects methylation, decreases expression, increases expression	5
Valproic Acid	increases expression, affects expression, affects cotreatment	5
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Vehicle Emissions	increases abundance, decreases expression, decreases reaction	2
Tretinoin	increases expression	2
Particulate Matter	increases abundance, decreases expression, decreases reaction	2
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
kojic acid	increases expression	1
terbufos	increases methylation	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
cupric chloride	decreases expression	1
mercuric bromide	increases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118992	Binding	Binding affinity to ESRP1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.