EML1

Chr 14AR

EMAP like 1

Also known as: BH, ELP79, EMAP, EMAP-1, EMAPL

NCBI Gene: 2009ENSG00000066629UniProt: O00423

Human echinoderm microtubule-associated protein-like is a strong candidate for the Usher syndrome type 1A gene. Usher syndromes (USHs) are a group of genetic disorders consisting of congenital deafness, retinitis pigmentosa, and vestibular dysfunction of variable onset and severity depending on the genetic type. The disease process in USHs involves the entire brain and is not limited to the posterior fossa or auditory and visual systems. The USHs are catagorized as type I (USH1A, USH1B, USH1C, USH1D, USH1E and USH1F), type II (USH2A and USH2B) and type III (USH3). The type I is the most severe form. Gene loci responsible for these three types are all mapped. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Band heterotopiaMIM #600348
AR
278
ClinVar variants
40
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EML1
🧬
Gene-Disease Validity (ClinGen)
band heterotopia of brain · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 110 VUS of 278 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.996
Z-score 5.63
OE 0.15 (0.09–0.28)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.45Z-score
OE missense 0.68 (0.62–0.75)
326 obs / 476.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.09–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.62–0.75)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 8 / 51.6Missense obs/exp: 326 / 476.6Syn Z: 0.74

ClinVar Variant Classifications

278 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic4
VUS110
Likely Benign76
Benign52
36
Pathogenic
4
Likely Pathogenic
110
VUS
76
Likely Benign
52
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
31
0
36
Likely Pathogenic
0
1
3
0
4
VUS
0
99
10
1
110
Likely Benign
0
2
26
48
76
Benign
0
3
40
9
52
Total410611058278

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

View in ClinVar →

Protein Context — Lollipop Plot

EML1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Band heterotopia

MIM #600348

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
EML1-associated brain overgrowth syndrome with ribbon-like heterotopia.
Oegema R et al.·Am J Med Genet C Semin Med Genet
2019Review
Novel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development.
Romero DM et al.·Nat Commun
2022
Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.
Kielar M et al.·Nat Neurosci
2014Functional
Mutations in the Heterotopia Gene Eml1/EML1 Severely Disrupt the Formation of Primary Cilia.
Uzquiano A et al.·Cell Rep
2019Case report
MSN/STAT3 drives cancer stemness and chemoresistance via IL-6/LPAR1 ligand receptor complex in triple-negative breast cancer.
Lee CH et al.·Breast Cancer Res
2025
A novel missense variant in the EML1 gene associated with bilateral ribbon-like subcortical heterotopia leads to ciliary defects.
Markus F et al.·J Hum Genet
2021
Recognisable Neuroradiological Findings in Five Neurogenetic Disorders.
Rosenblum J et al.·Clin Genet
2025Review
Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32).
De Keersmaecker K et al.·Blood
2005Case report
The genetic landscape of familial congenital hydrocephalus.
Shaheen R et al.·Ann Neurol
2017
Subcortical heterotopic gray matter brain malformations: Classification study of 107 individuals.
Oegema R et al.·Neurology
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools