ZMPSTE24

Chr 1AR

zinc metallopeptidase STE24

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

The protein is a zinc metalloproteinase that processes prelamin A to form mature lamin A on the inner nuclear membrane and clears clogged translocons on the endoplasmic reticulum. Mutations cause mandibuloacral dysplasia with type B lipodystrophy and restrictive dermopathy, both inherited in an autosomal recessive pattern. The gene shows extremely low constraint to loss-of-function variation (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.332 OMIM phenotypes
Clinical SummaryZMPSTE24
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Gene-Disease Validity (ClinGen)
obsolete lethal restrictive dermopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — ZMPSTE24
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.000
Z-score 0.26
OE 0.94 (0.681.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.93 (0.841.04)
228 obs / 244.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.94 (0.681.33)
00.351.4
Missense OE0.93 (0.841.04)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 24 / 25.4Missense obs/exp: 228 / 244.4Syn Z: 0.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveZMPSTE24-related lethal restrictive dermopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7228th %ile
GOF
0.6736th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
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 ↗