MPHOSPH8

Chr 13

M-phase phosphoprotein 8

Also known as: HSMPP8, TWA3, mpp8

MPHOSPH8 encodes a heterochromatin component that recognizes methylated histone H3K9 and promotes epigenetic gene silencing through recruitment of DNA methyltransferases and chromatin remodeling complexes, particularly silencing transposable elements and interferon-stimulated genes. Mutations cause neurodevelopmental disorder with epilepsy, spasticity, and brain abnormalities, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.525), consistent with its critical role in chromatin regulation and neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.53
Clinical SummaryMPHOSPH8
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.001
Z-score 3.81
OE 0.32 (0.210.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.08Z-score
OE missense 0.85 (0.790.93)
377 obs / 441.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.210.53)
00.351.4
Missense OE0.85 (0.790.93)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 12 / 37.0Missense obs/exp: 377 / 441.1Syn Z: -0.84

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MPHOSPH8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC