PUS7

Chr 7AR

pseudouridine synthase 7

Also known as: IDDABS

NCBI Gene: 54517ENSG00000091127UniProt: Q96PZ0

Enables enzyme binding activity and tRNA pseudouridine(13) synthase activity. Involved in several processes, including pseudouridine synthesis; regulation of hematopoietic stem cell differentiation; and regulation of mesoderm development. Is active in nucleus. Implicated in intellectual developmental disorder with abnormal behavior, microcephaly, and short stature. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with abnormal behavior, microcephaly, and short statureMIM #618342
AR
187
ClinVar variants
58
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PUS7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 Pathogenic / Likely Pathogenic· 100 VUS of 187 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.37
OE 0.57 (0.40–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.43Z-score
OE missense 0.79 (0.71–0.87)
281 obs / 356.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.40–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.71–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 20 / 35.2Missense obs/exp: 281 / 356.9Syn Z: -0.45

ClinVar Variant Classifications

187 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic19
VUS100
Likely Benign16
Benign11
Conflicting2
39
Pathogenic
19
Likely Pathogenic
100
VUS
16
Likely Benign
11
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
28
0
39
Likely Pathogenic
9
5
5
0
19
VUS
2
87
11
0
100
Likely Benign
0
4
3
9
16
Benign
0
1
7
3
11
Conflicting
—2
Total22975412187

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

View in ClinVar →

Protein Context — Lollipop Plot

PUS7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PUS7-related intellectual disability with speech delay, microcephaly, short stature, and aggressive behavior

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature

MIM #618342

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.
Li G et al.·Science
2025
A PUS7 gene pathogenic variant causing self-injurious behavior, sleep disturbances, and developmental delay: A case report.
Muda A et al.·Am J Med Genet A
2023Case report
Multi-omics analysis identifies PUS7 as an immune modulator driving NETs-mediated macrophage polarization in pancreatic cancer.
Fang J et al.·Clin Transl Med
2026
HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance.
Song D et al.·J Exp Clin Cancer Res
2021
PUS7 mutations impair pseudouridylation in humans and cause intellectual disability and microcephaly.
Shaheen R et al.·Hum Genet
2019Case report
PUS7 deficiency in human patients causes profound neurodevelopmental phenotype by dysregulating protein translation.
Han ST et al.·Mol Genet Metab
2022Cohort
Early Progression Prediction in Korean Crohn's Disease Using a Korean-Specific PrediXcan Model.
Kim TW et al.·Int J Mol Sci
2025Functional
Pseudouridylate Synthase 7 Promotes Cell Proliferation and Invasion in Colon Cancer Through Activating PI3K/AKT/mTOR Signaling Pathway.
Du J et al.·Dig Dis Sci
2022
Integrative analysis of RNA modification-related gene PUS7 in diagnosis, prognosis, and tumor microenvironment of hepatocellular carcinoma.
Chen L et al.·Comput Methods Programs Biomed
2026
Higher expression of pseudouridine synthase 7 promotes non-small cell lung cancer progression and suggests a poor prognosis.
Zhang G et al.·J Cardiothorac Surg
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools