AJAP1

Chr 1

adherens junctions associated protein 1

Also known as: MOT8, SHREW-1, SHREW1

NCBI Gene: 55966 ENSG00000196581 UniProt: Q9UKB5 OMIM: 610972

AJAP1 encodes a protein that enables beta-catenin binding and regulates cell adhesion and migration, particularly in epithelial cell differentiation and cell-matrix interactions. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.19), indicating that complete protein loss is poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables beta-catenin binding activity. Involved in negative regulation of cell-matrix adhesion; negative regulation of wound healing; and regulation of polarized epithelial cell differentiation. Located in several cellular components, including adherens junction; basolateral plasma membrane; and cell-cell contact zone. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— AJAP1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

63 VUS of 79 total submissions

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?

0.19LOEUF

pLI 0.995

Z-score 3.65

OE 0.00 (0.00–0.19)

Highly constrained

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

Missense Constraint?

0.94Z-score

OE missense 0.83 (0.74–0.93)

200 obs / 240.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.19)

0≤0.351.4

Missense OE?0.83 (0.74–0.93)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 0 / 15.5Missense obs/exp: 200 / 240.9Syn Z: 0.16

This gene — mechanism propensity

0.3991th %ile

GOF

0.4875th %ile

LOF

0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

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

79 submitted variants in ClinVar

ClinVar

Classification Summary

VUS63

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	61	1	63
Likely Benign	0	2	1	3
Benign	0	2	0	2
Total	1	65	2	68

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

View in ClinVar →

79 pathogenic / likely-pathogenic (of 86) ClinVar copy-number / structural variants overlap AJAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →