ZSWIM6

Chr 5AD

zinc finger SWIM-type containing 6

NCBI Gene: 57688ENSG00000130449UniProt: Q9HCJ5

involved in nervous system development, important for striatal morphology and motor regulation

Primary Disease Associations & Inheritance

Acromelic frontonasal dysostosisMIM #603671
AD
Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic featuresMIM #617865
AD
595
ClinVar variants
3
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ZSWIM6
🧬
Gene-Disease Validity (ClinGen)
acromelic frontonasal dysostosis · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
3 Pathogenic / Likely Pathogenic· 315 VUS of 595 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.07LOEUF
pLI 1.000
Z-score 6.17
OE 0.00 (0.00–0.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
4.18Z-score
OE missense 0.51 (0.46–0.56)
291 obs / 572.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.00 (0.00–0.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.46–0.56)
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.0.89
0≤1.21.6
LoF obs/exp: 0 / 44.3Missense obs/exp: 291 / 572.0Syn Z: 1.28

ClinVar Variant Classifications

595 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS315
Likely Benign216
Benign42
Conflicting19
2
Pathogenic
1
Likely Pathogenic
315
VUS
216
Likely Benign
42
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
1
0
2
Likely Pathogenic
0
1
0
0
1
VUS
8
276
26
5
315
Likely Benign
2
17
76
121
216
Benign
0
17
19
6
42
Conflicting
—19
Total11311122132595

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

View in ClinVar →

Protein Context — Lollipop Plot

ZSWIM6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ZSWIM6-related acromelic frontonasal dysostosis

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Acromelic frontonasal dysostosis

MIM #603671

Molecular basis of disorder known

Autosomal dominant

Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features

MIM #617865

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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