ZSWIM5

Chr 1

zinc finger SWIM-type containing 5

NCBI Gene: 57643 ENSG00000162415 UniProt: Q9P217 OMIM: 620132

The ZSWIM5 protein is predicted to bind zinc ions and is located in the extracellular space. Mutations in this gene cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.4), consistent with its role in neurodevelopment.

OMIM ResearchSummary from RefSeq

Predicted to enable zinc ion binding activity. Located in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.40

Clinical Summary— ZSWIM5

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

149 VUS of 166 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.040

Z-score 5.10

OE 0.26 (0.17–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.32Z-score

OE missense 0.74 (0.69–0.80)

471 obs / 635.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.17–0.40)

0≤0.351.4

Missense OE?0.74 (0.69–0.80)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 14 / 54.8Missense obs/exp: 471 / 635.3Syn Z: 2.68

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

VUS149

Likely Benign2

Benign1

149

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	149	149
Likely Benign	2	2
Benign	1	1
Total	152	152

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap ZSWIM5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →