BAIAP2

Chr 17AD

BAR/IMD domain containing adaptor protein 2

Also known as: BAP2, DEE120, FLAF3, IRSP53, WAML

NCBI Gene: 10458ENSG00000175866UniProt: Q9UQB8

The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor (BAI1)-binding protein. This adaptor protein links membrane bound G-proteins to cytoplasmic effector proteins. This protein functions as an insulin receptor tyrosine kinase substrate and suggests a role for insulin in the central nervous system. It also associates with a downstream effector of Rho small G proteins, which is associated with the formation of stress fibers and cytokinesis. This protein is involved in lamellipodia and filopodia formation in motile cells and may affect neuronal growth-cone guidance. This protein has also been identified as interacting with the dentatorubral-pallidoluysian atrophy gene, which is associated with an autosomal dominant neurodegenerative disease. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 120MIM #621468
AD
119
ClinVar variants
24
Pathogenic / LP
0.46
pLI score
0
Active trials
Clinical Summary— BAIAP2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 77 VUS of 119 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.462
Z-score 3.81
OE 0.22 (0.12–0.43)
Moderately constrained

More LoF-intolerant than ~75% 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.
2.06Z-score
OE missense 0.69 (0.63–0.77)
249 obs / 358.8 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.0.22 (0.12–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.63–0.77)
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.1.34
0≤1.21.6
LoF obs/exp: 6 / 27.6Missense obs/exp: 249 / 358.8Syn Z: -3.41

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS77
Likely Benign10
Benign8
23
Pathogenic
1
Likely Pathogenic
77
VUS
10
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
6
17
0
23
Likely Pathogenic
0
0
1
0
1
VUS
1
67
9
0
77
Likely Benign
0
4
2
4
10
Benign
0
0
1
7
8
Total1773011119

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

View in ClinVar →

Protein Context — Lollipop Plot

BAIAP2 · 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

Developmental and epileptic encephalopathy 120

MIM #621468

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — BAIAP2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A lissencephaly-associated BAIAP2 variant causes defects in neuronal migration during brain development.
Tsai MH et al.·Development
2024
BAIAP2 is related to emotional modulation of human memory strength.
Luksys G et al.·PLoS One
2014
Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults.
Hasler R et al.·Psychiatry Res Neuroimaging
2017Functional
HNF1β-associated cyst development and electrolyte disturbances are not explained by BAIAP2L2 expression.
Tholen LE et al.·FASEB J
2023
De novo DNA methylation induced by circulating extracellular vesicles from acute coronary syndrome patients.
Schiano C et al.·Atherosclerosis
2022Cohort
GCHFR-gut microbiota axis in gout: an integrative multi-omics and Mendelian randomization study with clinical and molecular validation.
Zhao Y et al.·Int Immunopharmacol
2026
BAIAP2 exhibits association to childhood ADHD especially predominantly inattentive subtype in Chinese Han subjects.
Liu L et al.·Behav Brain Funct
2013
A novel autophagy-related lncRNA prognostic risk model for breast cancer.
Li X et al.·J Cell Mol Med
2021Functional
Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease.
Lakshman Kumar P et al.·J Cachexia Sarcopenia Muscle
2021Functional
Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies.
Bonvicini C et al.·Mol Psychiatry
2016Meta-analysis
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