ABLIM2

Chr 4

actin binding LIM protein family member 2

The protein acts as a scaffold protein that binds actin filaments and stimulates transcriptional activity through the SRF pathway, playing a role in cellular structure and gene regulation. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features. This gene is highly constrained against loss-of-function variants, suggesting that complete protein loss is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
75
P/LP submissions
0%
P/LP missense
0.47
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryABLIM2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
75 unique Pathogenic / Likely Pathogenic· 125 VUS of 241 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.005
Z-score 4.37
OE 0.29 (0.190.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.17Z-score
OE missense 0.98 (0.901.06)
391 obs / 400.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.190.47)
00.351.4
Missense OE0.98 (0.901.06)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 13 / 44.5Missense obs/exp: 391 / 400.4Syn Z: -1.35
DN
0.78top 25%
GOF
0.74top 25%
LOF
0.3843th %ile

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

DNprediction above median
GOFprediction 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

241 submitted variants in ClinVar

Classification Summary

Pathogenic72
Likely Pathogenic3
VUS125
Likely Benign7
Benign2
72
Pathogenic
3
Likely Pathogenic
125
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
72
0
72
Likely Pathogenic
0
0
3
0
3
VUS
0
119
6
0
125
Likely Benign
0
4
0
3
7
Benign
0
0
2
0
2
Total0123833209

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

View in ClinVar →

Protein Context — Lollipop Plot

ABLIM2 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC