ESPN

espin, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 1:6424775-6461367

Previous symbols: [ "DFNB36" ]

Links

ENSG00000187017 ∙ NCBI:83715 ∙ OMIM:606351 ∙ HGNC:13281 ∙ Uniprot:B1AK53 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 36 (Strong), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 36 (Limited), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 36 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• Usher syndrome type 1 (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 36 (Limited), mode of inheritance: AD
• Usher syndrome type 3B (Limited), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 36 (Strong), mode of inheritance: AR
• Usher syndrome, type 1M (Limited), mode of inheritance: Unknown
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant, without vestibular involvement; Deafness, autosomal recessive 36, with or without vestibular involvement; Usher syndrome, type 1M	AD/AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	15286153; 15930085; 18973245; 29572253

ClinVar

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

• not provided (304 variants)
• Inborn genetic diseases (48 variants)
• not specified (38 variants)
• Autosomal recessive nonsyndromic hearing loss 36 (15 variants)
• Autosomal recessive nonsyndromic hearing loss 36;Usher syndrome, type 1M (4 variants)
• Usher syndrome, type 1M (2 variants)
• Deafness, without vestibular involvement, autosomal dominant (2 variants)
• Sensorineural hearing loss disorder (2 variants)
• Usher syndrome, type 1M;Autosomal recessive nonsyndromic hearing loss 36 (2 variants)
• Usher syndrome type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ESPN 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	69	2	73
missense		1	155	14	7	177
nonsense	2	3	1			6
start loss			1			1
frameshift	2					2
inframe indel	1	1	5	2		9
splice donor/acceptor (+/-2bp)	1	1				2
splice region				9	1	10
non coding			1	36	31	68
Total	6	6	165	121	40

Highest pathogenic variant AF is 0.0000132

Variants in ESPN

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

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

Position	Type	Phenotype	Significance	ClinVar
1-6424818-C-T			Benign (Apr 10, 2019)
1-6424820-A-G			Benign (Mar 31, 2019)
1-6424902-A-G			Likely benign (Aug 21, 2018)
1-6424907-G-A			Likely benign (Jun 05, 2019)
1-6424943-C-T			Likely benign (Aug 06, 2018)
1-6424956-A-C			Uncertain significance (Oct 27, 2021)
1-6424981-C-G			Uncertain significance (Jul 25, 2019)
1-6424983-G-C			Uncertain significance (Jun 01, 2016)
1-6424991-G-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
1-6425006-G-A			Likely benign (May 04, 2021)
1-6425011-G-A			Uncertain significance (Jun 13, 2022)
1-6425022-G-A		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
1-6425039-G-T			Likely benign (May 28, 2022)
1-6425049-C-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
1-6425050-G-A			Uncertain significance (Jul 05, 2022)
1-6425054-C-T			Likely benign (Sep 08, 2023)
1-6425085-G-T			Uncertain significance (Oct 03, 2022)
1-6425130-G-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
1-6425145-G-T			Uncertain significance (Jun 20, 2021)
1-6425150-C-G			Likely benign (Jan 14, 2023)
1-6425155-C-T			Uncertain significance (Nov 20, 2023)
1-6425155-CCCGC-TCCAT			Uncertain significance (Jan 24, 2023)
1-6425156-C-T			Likely benign (Aug 04, 2023)
1-6425172-C-G			Uncertain significance (Jul 17, 2023)
1-6425191-C-G			Uncertain significance (Nov 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ESPN	protein_coding	protein_coding	ENST00000377828	13	36583

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.87e-9	0.910	125690	0	53	125743	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0787	440	435	1.01	0.0000266	5303
Missense in Polyphen		173	168.45	1.027		1821
Synonymous	0.805	183	197	0.927	0.0000131	1817
Loss of Function	1.83	18	28.6	0.630	0.00000128	358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000900	0.000880
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.0000558	0.0000544
Finnish	0.000151	0.000139
European (Non-Finnish)	0.0000928	0.0000791
Middle Eastern	0.0000558	0.0000544
South Asian	0.000364	0.000327
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Multifunctional actin-bundling protein. Plays a major role in regulating the organization, dimension, dynamics and signaling capacities of the actin filament-rich microvilli in the mechanosensory and chemosensory cells. Required for the assembly and stabilization of the stereociliary parallel actin bundles. Plays a crucial role in the formation and maintenance of inner ear hair cell stereocilia. Involved in the elongation of actin in stereocilia. In extrastriolar hair cells, required for targeting MYO3B to stereocilia tips, and for regulation of stereocilia diameter and staircase formation. {ECO:0000250|UniProtKB:Q9ET47}.
• Disease: DISEASE: Deafness, autosomal recessive, 36, with or without vestibular involvement (DFNB36) [MIM:609006]: A form of non- syndromic sensorineural 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. DFNB36 is characterized by prelingual, profound hearing loss, and vestibular areflexia in some patients. {ECO:0000269|PubMed:15286153, ECO:0000269|PubMed:15930085, ECO:0000269|PubMed:28281779}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.130

Haploinsufficiency Scores

• pHI: 0.0998
• hipred: N
• hipred_score: 0.427
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.370

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Espn
• Phenotype: hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype

Gene ontology

• Biological process: sensory perception of sound;locomotory behavior;parallel actin filament bundle assembly;actin filament bundle assembly;positive regulation of filopodium assembly;negative regulation of cytoskeleton organization
• Cellular component: cytoplasm;microvillus;brush border;filamentous actin;stereocilium tip
• Molecular function: SH3 domain binding;actin filament binding