SHQ1

protein-coding

SHQ1, H/ACA ribonucleoprotein assembly factor

Gene summary

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]

MANE transcript

NM_018130.3

Inheritance

ClinVar variants

P:7U:116B:18

Top phenotype

Dystonia 35, childhood-onset

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr3:72,749,277-72,861,914

External References & Databases

Ensembl (ENSG00000144736)

Transcript & Mutation Effects

hg38 • Region Span ~112.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with dystonia and seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859258

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with dystonia and seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859258

Submitter: PanelApp Australia

neurodevelopmental disorder with dystonia and seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859258

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Dystonia 35, childhood-onsetAR

Manifestation: Neurologic

Intervention: Neurologic

Rationale: The condition involves early-onset dystonia, and medical management (with L-DOPA) has been descriebd as beneficial

Refs: 29178645; 34542157

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHQ1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 107

not providedTotal: 26

Neurodevelopmental disorder with dystonia and seizuresTotal: 13

SHQ1-related disorderTotal: 5

Dystonia 35, childhood-onsetTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018130.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	5 clinvar	1 clinvar	9
missense		4 clinvar	103 clinvar	8 clinvar	4 clinvar	119
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift		1 clinvar	5 clinvar			6
splice donor/acceptor (+/-2bp)	1 clinvar		3 clinvar			4
Total	1	6	116	13	5	141

Highest pathogenic variant AF is 0.0011518738

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018130.3	RefSeq	NP_060600.2	11	MANE Select
ENST00000325599.13	Ensembl	ENSP00000315182.8	11	MANE Select
ENST00000444040.6	Ensembl	ENSP00000402447.2	2	Standard
ENST00000463369.5	Ensembl	ENSP00000417452.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

box H/ACA snoRNP assembly
ribonucleoprotein complex assembly
positive regulation of apoptotic process
positive regulation of telomerase RNA localization to Cajal body
negative regulation of rRNA processing

Molecular Function

protein binding
unfolded protein binding

Cellular Component

nucleoplasm
nucleolus
cytoplasm
cytosol
Cajal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325599
Coding exons: 11
Length: 112638
Individuals with no LoFs: 125487
Homozygous LoFs: 0
Heterozygous LoFs: 260
Defined: 125747
p: 0.00103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.432	327	306	1.07	0.0000155	3770
Missense (PolyPhen)		92	85.27	1.0789		1072
Synonymous	-0.0312	117	117	1.00	0.00000600	1095
Loss of Function	1.04	19	24.6	0.773	0.00000133	291

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00075	0.00075	rare
Ashkenazi Jewish	0.00020	0.000099	rare
East Asian	0.0011	0.0011	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.0016	0.0016	notable
South Asian	0.00052	0.00052	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA. {ECO:0000269|PubMed:19383767}.;

Intolerance Scores

LoFtool: 0.907
RVIS EVS: 0.89
RVIS percentile EVS: 89.19

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.774

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium