ESRP1

Chr 8AR

epithelial splicing regulatory protein 1

Also known as: DFNB109, RBM35A, RMB35A

ESRP1 encodes an mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms and controls splicing of genes involved in inner ear development and auditory hair cell differentiation. Mutations cause autosomal recessive deafness (DFNB109). The gene is highly constrained against loss-of-function variants, suggesting that complete loss of function is likely pathogenic.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 109MIM #618013
AR
0
Active trials
29
Pubs (1 yr)
41
P/LP submissions
3%
P/LP missense
0.24
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryESRP1
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 68 VUS of 153 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.999
Z-score 5.17
OE 0.10 (0.050.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.27Z-score
OE missense 0.67 (0.600.74)
245 obs / 367.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.050.24)
00.351.4
Missense OE0.67 (0.600.74)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 4 / 38.8Missense obs/exp: 245 / 367.2Syn Z: 0.10
DN
0.3892th %ile
GOF
0.4480th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

153 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic1
VUS68
Likely Benign16
Benign10
39
Pathogenic
1
Likely Pathogenic
68
VUS
16
Likely Benign
10
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
37
0
39
Likely Pathogenic
0
0
1
0
1
VUS
0
67
1
0
68
Likely Benign
0
3
2
11
16
Benign
0
1
4
5
10
Total1724516134

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ESRP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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