SHQ1

Chr 3AR

SHQ1, H/ACA ribonucleoprotein assembly factor

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

NCBI Gene: 55164 ENSG00000144736 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.132 OMIM phenotypes

Clinical Summary— SHQ1

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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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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 OE?0.77 (0.54–1.13)

0≤0.351.4

Missense OE?1.07 (0.98–1.17)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 19 / 24.6Missense obs/exp: 327 / 305.7Syn Z: -0.03

This gene — mechanism propensity

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.