GeneBe

QRICH1

protein-coding

glutamine rich 1, the group of Caspase recruitment domain containing

Gene summary

Enables DNA binding activity. Involved in intracellular signal transduction; positive regulation of DNA-templated transcription; and positive regulation of apoptotic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_198880.3

Inheritance

AD

ClinVar variants

P:85U:161B:21

Top phenotype

Ververi-Brady syndrome

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr3:49,029,707-49,094,363

External References & Databases

Ensembl (ENSG00000198218)NCBI Gene (54870)OMIM (617387)HGNC:24713GenCCUniProt (Q2TAL8)AlphaFoldClinVar (QRICH1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~64.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ververi-Brady syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0060707

Submitter: Labcorp Genetics (formerly Invitae)

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

Ververi-Brady syndrome 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0060707

Submitter: Ambry Genetics

Ververi-Brady syndrome 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0060707

Submitter: Illumina

Ververi-Brady syndrome 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0060707

Submitter: G2P

syndromic complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0800439

Submitter: ClinGen

*QRICH1* was first reported in relation to autosomal dominant syndromic complex neurodevelopmental disorder in 2018 (Ververi et al., PMID: 28692176). *QRICH1* encodes a protein that functions as a mediator in the integrated stress response by controlling transcription of protein homeostasis under endoplasmic reticulum stress. Clinical features in affected individuals include developmental delay, intellectual disability, mild dysmorphic facial features, hypotonia, short stature, autism spectrum disorder, and seizures (PMID: 34859529). Additional, more variable features may include scoliosis, cardiac, renal and structural brain abnormalities. Seven variants (nonsense, frameshift, and missense) reported in 7 probands in 3 publications (PMIDs: 28692176, 30281152, 33009816) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by experimental evidence, including a mouse model (PMID: 30281152). In summary, there is definitive evidence supporting the relationship between *QRICH1* and autosomal dominant syndromic complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on June 15, 2022 (SOP version 9).

Ververi-Brady syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0060707

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ververi-Brady syndromeAD

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28692176; 30281152Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to QRICH1 variants in ClinVar

10 Conditions Cataloged
not providedTotal: 115
Ververi-Brady syndromeTotal: 77
Inborn genetic diseasesTotal: 73
QRICH1-related disorderTotal: 22
Ververi-Brady syndrome 1Total: 12
not specifiedTotal: 9
Intellectual disabilityTotal: 3
Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198880.3. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
18
clinvar
1
clinvar
 21
missense
17
clinvar
150
clinvar
2
clinvar
 169
nonsense
18
clinvar
10
clinvar
1
clinvar
 29
start loss
1
clinvar
 1
frameshift
22
clinvar
11
clinvar
4
clinvar
 37
splice donor/acceptor (+/-2bp)
3
clinvar
3
clinvar
4
clinvar
 10
Total4441161201267

Highest pathogenic variant AF is 0.0000013944804

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_198880.3RefSeqNP_942581.19MANE Select
ENST00000395443.7EnsemblENSP00000378830.29MANE Select
NM_001320580.2RefSeqNP_001307509.19Standard
NM_001320581.2RefSeqNP_001307510.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • regulation of transcription by RNA polymerase II
  • biological_process
  • regulation of cell morphogenesis

Molecular Function

  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • molecular_function
  • protein binding

Cellular Component

  • cellular_component
  • nucleus
  • nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000395443
Coding exons
9
Length
64657
Individuals with no LoFs
125741
Homozygous LoFs
0
Heterozygous LoFs
6
Defined
125747
p
0.0000239
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.712114270.4950.00002305050
Missense (PolyPhen)38101.390.374781229
Synonymous-0.4701781701.050.000009621566
Loss of Function4.98538.20.1310.00000188388

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000550.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000270.000026rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec
0.0751

Intolerance Scores

LoFtool
0.0214
RVIS EVS
-0.47
RVIS percentile EVS
23.25

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.754

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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