PUM3

Chr 9

pumilio RNA binding family member 3

Also known as: HA-8, HLA-HA8, KIAA0020, PEN, PUF-A, PUF6, XTP5

NCBI Gene: 9933 ENSG00000080608 UniProt: Q15397 OMIM: 609960

The protein binds RNA and regulates translation, while also inhibiting PARP1 poly(ADP-ribosyl)ation activity and protecting PARP1 from degradation following DNA damage. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in infancy with severe intellectual disability, seizures, and progressive brain atrophy. This gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Predicted to be involved in regulation of translation. Located in chromosome; endoplasmic reticulum; and nuclear lumen. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.38

Clinical Summary— PUM3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

125 VUS of 158 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.38LOEUF

pLI 0.000

Z-score -0.28

OE 1.05 (0.81–1.38)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.80Z-score

OE missense 1.43 (1.33–1.55)

472 obs / 329.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.05 (0.81–1.38)

0≤0.351.4

Missense OE?1.43 (1.33–1.55)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 38 / 36.2Missense obs/exp: 472 / 329.0Syn Z: -2.88

This gene — mechanism propensity

0.75top 25%

GOF

0.4184th %ile

LOF

0.3550th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

158 submitted variants in ClinVar

ClinVar

Classification Summary

VUS125

Likely Benign3

Benign3

125

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	125	125
Likely Benign	3	3
Benign	3	3
Total	131	131

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

View in ClinVar →

176 pathogenic / likely-pathogenic (of 197) ClinVar copy-number / structural variants overlap PUM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →