ESPNL

protein-coding

espin like, the group of Ankyrin repeat domain containing

Gene summary

Predicted to enable actin filament binding activity. Predicted to be involved in actin filament bundle assembly and sensory perception of sound. Predicted to be located in stereocilium tip. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_194312.4

Inheritance

—

ClinVar variants

U:253B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr2:238,100,340-238,133,287

External References & Databases

Ensembl (ENSG00000144488)

Transcript & Mutation Effects

hg38 • Region Span ~32.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ESPNL variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 255

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_194312.4. 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	2 clinvar		3
missense			248 clinvar	10 clinvar	2 clinvar	260
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	253	12	2	267

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_194312.4	RefSeq	NP_919288.2	9	MANE Select
ENST00000343063.8	Ensembl	ENSP00000339115.3	9	MANE Select
NM_001308370.2	RefSeq	NP_001295299.1	3	Standard
ENST00000409169.5	Ensembl	ENSP00000386577.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

sensory perception of sound
actin filament bundle assembly

Molecular Function

actin filament binding

Cellular Component

cytoplasm
filamentous actin
stereocilium tip

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343063
Coding exons: 9
Length: 33131
Individuals with no LoFs: 125312
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125404
p: 0.000367

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.494	614	649	0.945	0.0000468	6209
Missense (PolyPhen)		184	209.89	0.87665		2137
Synonymous	0.122	303	306	0.991	0.0000231	2206
Loss of Function	1.83	20	31.0	0.646	0.00000157	329

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.00056	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00047	0.00046	rare
South Asian	0.00030	0.00029	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to but does not cross-link actin. Required for the formation and maintenance of inner ear hair cell stereocilia and staircase formation. Essential for normal hearing. {ECO:0000250|UniProtKB:Q3UYR4}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.200

Gene Damage Prediction

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