PUM1

Chr 1AD

pumilio RNA binding family member 1

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

NCBI Gene: 9698 ENSG00000134644 UniProt: Q14671 OMIM: 607204

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the PUF family, evolutionarily conserved RNA-binding proteins related to the Pumilio proteins of Drosophila and the fem-3 mRNA binding factor proteins of C. elegans. The encoded protein contains a sequence-specific RNA binding domain comprised of eight repeats and N- and C-terminal flanking regions, and serves as a translational regulator of specific mRNAs by binding to their 3' untranslated regions. The evolutionarily conserved function of the encoded protein in invertebrates and lower vertebrates suggests that the human protein may be involved in translational regulation of embryogenesis, and cell development and differentiation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.131 OMIM phenotype

Clinical Summary— PUM1

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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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ClinVar Variants

23 unique Pathogenic / Likely Pathogenic· 249 VUS of 378 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 6.82

OE 0.05 (0.02–0.13)

Highly constrained

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

Missense Constraint?

4.42Z-score

OE missense 0.53 (0.48–0.57)

361 obs / 687.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.13)

0≤0.351.4

Missense OE?0.53 (0.48–0.57)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 3 / 60.0Missense obs/exp: 361 / 687.0Syn Z: 0.42

This gene — mechanism propensity

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 · 78% of P/LP variants are LoF · LOEUF 0.13

Literature Evidence

LOFA mild PUM1 mutation is associated with adult-onset ataxia, whereas haploinsufficiency causes developmental delay and seizures.1

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

References

1.PMID 29474920 ↗

ClinVar Variant Classifications

378 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic13

VUS249

Likely Benign45

Benign28

Conflicting7

Pathogenic

Likely Pathogenic

249

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	0	0	0	10
Likely Pathogenic	8	5	0	0	13
VUS	3	234	8	4	249
Likely Benign	0	11	11	23	45
Benign	0	1	23	4	28
Conflicting	—				7
Total	21	251	42	31	352

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap PUM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →