PUM1

Chr 1AD

pumilio RNA binding family member 1

Also known as: HSPUM, NEDMSF, PUMH, PUMH1, PUML1, SCA47

The PUM1 protein is an RNA-binding protein that regulates gene expression by binding to the 3' untranslated regions of target mRNAs and repressing their translation, playing critical roles in cell cycle regulation, DNA repair, and neuronal function. Mutations cause a neurodevelopmental disorder with motor abnormalities and facial dysmorphism with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating that proper PUM1 function is essential for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.131 OMIM phenotype
Clinical SummaryPUM1
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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 6.82
OE 0.05 (0.020.13)
Highly constrained

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

Missense Constraint
4.42Z-score
OE missense 0.53 (0.480.57)
361 obs / 687.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.05 (0.020.13)
00.351.4
Missense OE0.53 (0.480.57)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 3 / 60.0Missense obs/exp: 361 / 687.0Syn Z: 0.42
DN
0.3494th %ile
GOF
0.4184th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.13

Literature Evidence

LOFA mild PUM1 mutation is associated with adult-onset ataxia, whereas haploinsufficiency causes developmental delay and seizures.PMID:29474920

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PUM1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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