SHQ1

Chr 3AR

SHQ1, H/ACA ribonucleoprotein assembly factor

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

NCBI Gene: 55164ENSG00000144736UniProt: Q6PI26

SHQ1 assists in the assembly of H/ACA-box ribonucleoproteins that function in the processing of ribosomal RNAs, modification of spliceosomal small nuclear RNAs, and stabilization of telomerase (see MIM 602322) (Grozdanov et al., 2009 [PubMed 19383767]).[supplied by OMIM, Dec 2010]

Primary Disease Associations & Inheritance

?Dystonia 35, childhood-onsetMIM #619921
AR
Neurodevelopmental disorder with dystonia and seizuresMIM #619922
AR
159
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SHQ1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 107 VUS of 159 total submissions

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

Tolerant to missense variation

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.0.77 (0.54–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.98–1.17)
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.1.00
0≤1.21.6
LoF obs/exp: 19 / 24.6Missense obs/exp: 327 / 305.7Syn Z: -0.03

ClinVar Variant Classifications

159 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic3
VUS107
Likely Benign11
Benign6
Conflicting4
12
Pathogenic
3
Likely Pathogenic
107
VUS
11
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
11
0
12
Likely Pathogenic
0
1
2
0
3
VUS
4
98
5
0
107
Likely Benign
0
8
1
2
11
Benign
0
4
0
2
6
Conflicting
—4
Total5111194143

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Dystonia 35, childhood-onset

MIM #619921

Molecular basis of disorder known

Autosomal recessive

Neurodevelopmental disorder with dystonia and seizures

MIM #619922

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrative genomic profiling of human prostate cancer.
Taylor BS et al.·Cancer Cell
2010
Pathogenic SHQ1 variants result in disruptions to neuronal development and the dopaminergic pathway.
Chang CH et al.·Exp Neurol
2024
Biallelic SHQ1 variants in early infantile hypotonia and paroxysmal dystonia as the leading manifestation.
Chi CS et al.·Hum Genet
2023
β-Sitosterol attenuates anlotinib resistance in non-small cell lung cancer cells by inhibiting miR-181a-3p/SHQ1 signaling.
Wang LH et al.·Chem Biol Drug Des
2024
Compound heterozygous variants in SHQ1 are associated with a spectrum of neurological features, including early-onset dystonia.
Sleiman S et al.·Hum Mol Genet
2022
Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita.
Bizarro J et al.·Mol Genet Genomic Med
2017Case report
Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita.
Grozdanov PN et al.·Hum Mol Genet
2009
Novel Germline Mutations in DNA Damage Repair in Patients with Malignant Pleural Mesotheliomas.
Guo R et al.·J Thorac Oncol
2020Cohort
Reply to: "Early Onset Nonprogressive Generalized Dystonia Is Caused by Biallelic SHQ1 Variants".
Indelicato E et al.·Mov Disord
2023
Recurrent deletion of 3p13 targets multiple tumour suppressor genes and defines a distinct subgroup of aggressive ERG fusion-positive prostate cancers.
Krohn A et al.·J Pathol
2013
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