DAB1

Chr 1AD

DAB adaptor protein 1

DAB1 encodes a signaling adapter protein that mediates reelin signaling to regulate neuronal migration and differentiation during brain development. Mutations cause spinocerebellar ataxia 37, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.215), indicating that complete loss of function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.211 OMIM phenotype
Clinical SummaryDAB1
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.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 0.999
Z-score 4.67
OE 0.07 (0.030.21)
Highly constrained

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

Missense Constraint
1.52Z-score
OE missense 0.76 (0.690.85)
245 obs / 321.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.21)
00.351.4
Missense OE0.76 (0.690.85)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 2 / 29.3Missense obs/exp: 245 / 321.6Syn Z: 0.90
DN
0.3395th %ile
GOF
0.4481th %ile
LOF
0.65top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.21
GOF1 literature citation

Literature Evidence

GOFIn this regard, our data support that a gain-of-function mutation by upregulation of DAB1 alternate isoforms underlies SCA37 with mislocalization of Purkinje neurons in the cerebellar cortex reflecting improper positioning and selective migration deficits.PMID:29939198

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DAB1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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