DAB1

Chr 1AD

DAB adaptor protein 1

ENSG00000173406UniProt: O75553

Signaling adapter of the reelin-mediated signaling pathway, which regulates the migration and differentiation of postmitotic neurons during brain development. Mediates intracellular transduction of Reelin signaling following reelin (RELN)-binding to its receptor: acts by docking proteins through its phosphotyrosine residues and PID domain

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 37MIM #615945
AD
180
ClinVar variants
12
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DAB1
⚡
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
12 Pathogenic / Likely Pathogenic· 93 VUS of 180 total submissions
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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.
0.21LOEUF
pLI 0.999
Z-score 4.67
OE 0.07 (0.03–0.21)
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.
1.52Z-score
OE missense 0.76 (0.69–0.85)
245 obs / 321.6 exp
Tolerant

Mild missense constraint

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.0.07 (0.03–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.69–0.85)
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.0.90
0≤1.21.6
LoF obs/exp: 2 / 29.3Missense obs/exp: 245 / 321.6Syn Z: 0.90

ClinVar Variant Classifications

180 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS93
Likely Benign32
Benign40
Conflicting3
9
Pathogenic
3
Likely Pathogenic
93
VUS
32
Likely Benign
40
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
1
2
0
3
VUS
1
80
11
1
93
Likely Benign
0
12
5
15
32
Benign
0
6
32
2
40
Conflicting
—3
Total1995918180

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia 37

MIM #615945

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — DAB1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autosomal dominant cerebellar ataxias: new genes and progress towards treatments.
Coarelli G et al.·Lancet Neurol
2023Review
Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation.
Jossin Y·Biomolecules
2020Review
Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.
Lopera F et al.·Nat Med
2023Case report
Neuronal migration.
Lambert de Rouvroit C et al.·Mech Dev
2001Review
A neurodevelopmental epigenetic programme mediated by SMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastoma metastasis.
Zou H et al.·Nat Cell Biol
2023
ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer's disease.
Ramsden CE et al.·Acta Neuropathol Commun
2023
Characterisation and differential expression during development of a duplicate Disabled-1 (Dab1) gene from zebrafish.
Herrero-Turrión MJ et al.·Comp Biochem Physiol B Biochem Mol Biol
2010Functional
The Role of Prion Protein in Reelin/Dab1 Signaling: Implications for Neurodegeneration.
Rolle IG et al.·Viruses
2025
Autophagy markers expression pattern in developing liver of the yotari (dab1(-/-)) mice and humans.
Dražić Maras E et al.·Acta Histochem
2025
The gene encoding disabled-1 (DAB1), the intracellular adaptor of the Reelin pathway, reveals unusual complexity in human and mouse.
Bar I et al.·J Biol Chem
2003Functional
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