ERC1

Chr 12

ELKS/RAB6-interacting/CAST family member 1

Also known as: Cast2, ELKS, ERC-1, RAB6IP2

The protein is a regulatory subunit of the IKK complex and organizes the cytomatrix at nerve terminal active zones, regulating neurotransmitter release and vesicle trafficking. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be severely pathogenic.

Summary from RefSeq, UniProt
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0
Active trials
14
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.54
LOEUF
DN
Mechanism· predicted
Clinical SummaryERC1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.000
Z-score 4.43
OE 0.38 (0.280.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.45Z-score
OE missense 0.83 (0.780.90)
510 obs / 611.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.280.54)
00.351.4
Missense OE0.83 (0.780.90)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 23 / 60.0Missense obs/exp: 510 / 611.2Syn Z: -1.34
DN
0.78top 25%
GOF
0.5953th %ile
LOF
0.4135th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ERC1 · 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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