SHQ1

Chr 3AR

SHQ1, H/ACA ribonucleoprotein assembly factor

Also known as: DYT35, GRIM-1, NEDDS, Shq1p

NCBI Gene: 55164ENSG00000144736UniProt: Q6PI26OMIM: 613663

SHQ1 is required for the assembly and stabilization of H/ACA ribonucleoproteins that process ribosomal RNAs, modify spliceosomal RNAs, and stabilize telomerase. Mutations cause autosomal recessive neurodevelopmental disorder with dystonia and seizures, typically presenting in childhood. This gene is extremely intolerant to loss-of-function variants (pLI near 1), indicating that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.132 OMIM phenotypes
Clinical Summary— SHQ1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 109 VUS of 162 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
1.13LOEUF
pLI 0.000
Z-score 1.04
OE 0.77 (0.54–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.43Z-score
OE missense 1.07 (0.98–1.17)
327 obs / 305.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.77 (0.54–1.13)
0≤0.351.4
Missense OE1.07 (0.98–1.17)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 19 / 24.6Missense obs/exp: 327 / 305.7Syn Z: -0.03
DN
0.6358th %ile
GOF
0.4579th %ile
LOF
0.3355th %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

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic3
VUS109
Likely Benign12
Benign6
Conflicting4
12
Pathogenic
3
Likely Pathogenic
109
VUS
12
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
10
0
12
Likely Pathogenic
0
1
2
0
3
VUS
6
99
4
0
109
Likely Benign
0
8
1
3
12
Benign
0
4
0
2
6
Conflicting
—4
Total8112175146

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

View in ClinVar →

Protein Context — Lollipop Plot

SHQ1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients