ELFN1

Chr 7AR

extracellular leucine rich repeat and fibronectin type III domain containing 1

Also known as: DONDS, PPP1R28

NCBI Gene: 392617 ENSG00000225968 UniProt: P0C7U0 OMIM: 614964

ELFN1 encodes a postsynaptic protein that regulates synaptic transmission by inhibiting protein phosphatase 1 activity and modulating interneuron circuit dynamics in the central nervous system. Mutations cause autosomal recessive intellectual disability with seizures, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.153), indicating that complete loss of function is poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.151 OMIM phenotype

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.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.15)

0≤0.351.4

Missense OE?0.70 (0.64–0.76)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 0 / 19.6Missense obs/exp: 359 / 514.7Syn Z: -0.09

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateELFN1-related intellectual disability and epilepsyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.4587th %ile

GOF

0.6638th %ile

LOF

0.69top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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