DIP2A

Chr 21

DIP2 acetate--CoA ligase A

Also known as: C21orf106, DIP2

NCBI Gene: 23181ENSG00000160305UniProt: Q14689

DIP2A encodes a protein that catalyzes acetyl-CoA synthesis and promotes dendritic spine morphology and synaptic transmission, while also functioning as a cell surface receptor for follistatin-related protein FSTL1. Mutations cause autosomal recessive intellectual disability with seizures and brain abnormalities. This gene is highly constrained against loss-of-function variants, indicating that complete protein loss is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
83
P/LP submissions
0%
P/LP missense
0.35
LOEUF
DN
Mechanism· predicted
Clinical Summary— DIP2A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
81 unique Pathogenic / Likely Pathogenic· 242 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.35LOEUF
pLI 0.113
Z-score 6.13
OE 0.24 (0.16–0.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.62Z-score
OE missense 0.76 (0.72–0.81)
729 obs / 957.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.24 (0.16–0.35)
0≤0.351.4
Missense OE0.76 (0.72–0.81)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 18 / 75.4Missense obs/exp: 729 / 957.4Syn Z: 0.50
DN
0.6745th %ile
GOF
0.5759th %ile
LOF
0.4233th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic10
VUS242
Likely Benign29
Benign14
Conflicting2
71
Pathogenic
10
Likely Pathogenic
242
VUS
29
Likely Benign
14
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
71
0
71
Likely Pathogenic
2
0
8
0
10
VUS
2
216
22
2
242
Likely Benign
0
12
6
11
29
Benign
0
1
3
10
14
Conflicting
—2
Total422911023368

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

View in ClinVar →

Protein Context — Lollipop Plot

DIP2A · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients