ELFN1

Chr 7AR

extracellular leucine rich repeat and fibronectin type III domain containing 1

Also known as: DONDS, PPP1R28

NCBI Gene: 392617ENSG00000225968UniProt: P0C7U0

Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in synapse organization. Predicted to act upstream of or within several processes, including chemical synaptic transmission; synapse assembly; and visual perception. Predicted to be located in dendrite and excitatory synapse. Predicted to be active in several cellular components, including axon terminus; glutamatergic synapse; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2025]

Primary Disease Associations & Inheritance

Dursun-Ozgul neurodevelopmental syndromeMIM #621344
AR
256
ClinVar variants
45
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ELFN1
⚡
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
45 Pathogenic / Likely Pathogenic· 178 VUS of 256 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.
0.15LOEUF
pLI 0.999
Z-score 4.10
OE 0.00 (0.00–0.15)
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.
2.44Z-score
OE missense 0.70 (0.64–0.76)
359 obs / 514.7 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.0.00 (0.00–0.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.64–0.76)
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.1.01
0≤1.21.6
LoF obs/exp: 0 / 19.6Missense obs/exp: 359 / 514.7Syn Z: -0.09

ClinVar Variant Classifications

256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic2
VUS178
Likely Benign18
Benign13
Conflicting2
43
Pathogenic
2
Likely Pathogenic
178
VUS
18
Likely Benign
13
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
40
0
43
Likely Pathogenic
1
0
1
0
2
VUS
0
159
19
0
178
Likely Benign
0
5
1
12
18
Benign
0
2
0
11
13
Conflicting
—2
Total31676123256

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

View in ClinVar →

Protein Context — Lollipop Plot

ELFN1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ELFN1-related intellectual disability and epilepsy

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
start lostmissense variantinframe deletionframeshift variant NMD escaping

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dursun-Ozgul neurodevelopmental syndrome

MIM #621344

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ELFN1 deficiency: The mechanistic basis and phenotypic spectrum of a neurodevelopmental disorder with epilepsy.
Dore R et al.·Genet Med
2025
Exploring the dark genome: implications for precision medicine.
Oprea TI·Mamm Genome
2019Review
Biallelic mutations in ELFN1 gene associated with developmental and epileptic encephalopathy and joint laxity.
Dursun A et al.·Eur J Med Genet
2021
ELFN1 is a new extracellular matrix (ECM)-associated protein.
Ayhan S et al.·Life Sci
2024
Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome.
Akçimen F et al.·Ann Neurol
2024Meta-analysis
Epigenetic heterogeneity hotspots in human liver disease progression.
Hlady RA et al.·Hepatology
2025
A long non-coding RNA, ELFN1-AS1, sponges miR-1250 to upregulate MTA1 to promote cell proliferation, migration and invasion, and induce apoptosis in colorectal cancer.
Zhai LQ et al.·Eur Rev Med Pharmacol Sci
2021
m6A-related lncRNAs as potential biomarkers and the lncRNA ELFN1-AS1/miR-182-5p/BCL-2 regulatory axis in diffuse large B-cell lymphoma.
Yang Q et al.·J Cell Mol Med
2024
[High expression of ELFN1 is a prognostic biomarker and promotes proliferation and metastasis of colorectal cancer cells].
Wang K et al.·Nan Fang Yi Ke Da Xue Xue Bao
2025
Comprehensive Analysis of Enhancer RNAs Identifies LINC00689 and ELFN1-AS1 as Novel Prognostic Biomarkers in Uveal Melanoma.
Zhao S et al.·Dis Markers
2022
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