ZMPSTE24

Chr 1

zinc metallopeptidase STE24

Also known as: FACE-1, FACE1, HGPS, PRO1, RSDM1, STE24, Ste24p

NCBI Gene: 10269ENSG00000084073UniProt: O75844

This gene encodes a member of the peptidase M48A family. The encoded protein is a zinc metalloproteinase involved in the two step post-translational proteolytic cleavage of carboxy terminal residues of farnesylated prelamin A to form mature lamin A. Mutations in this gene have been associated with mandibuloacral dysplasia and restrictive dermopathy. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMandibuloacral dysplasia with type B lipodystrophy
UniProtRestrictive dermopathy 1

Clinical highlights

Gene-disease validity (ClinGen)
mandibuloacral dysplasia with type B lipodystrophy · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
25
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.33
LOEUF
LOF
Mechanism· G2P
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GeneReview available — ZMPSTE24
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.33LOEUF
pLI 0.000
Z-score 0.26
OE 0.94 (0.68–1.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.37Z-score
OE missense 0.93 (0.84–1.04)
228 obs / 244.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.94 (0.68–1.33)
0≤0.351.4
Missense OE?0.93 (0.84–1.04)
0≤0.61.4
Synonymous OE?0.88
0≤1.21.6
LoF obs/exp: 24 / 25.4Missense obs/exp: 228 / 244.4Syn Z: 0.91

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ZMPSTE24 · protein map & ClinVar variants

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

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