Ververi-Brady syndrome 1

Summary

Ververi-Brady syndrome 1 (MONDO:0060707) is a disease caused by QRICH1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: QRICH1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Ververi-Brady syndrome 1
Mondo ID	MONDO:0060707
OMIM	617982
Orphanet	580940
GARD	0018015
Is cancer (heuristic)	no

Also known as: VERBRAS1 · Ververi-Brady syndrome 1

Data availability: 7 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › autosomal dominant syndromic intellectual disability › Ververi-Brady syndrome 1

Related subtypes (33): Myhre syndrome, KBG syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations, Mowat-Wilson syndrome, Schinzel-Giedion syndrome, intellectual disability-sparse hair-brachydactyly syndrome, Pierpont syndrome, Bohring-Opitz syndrome, hereditary cryohydrocytosis with reduced stomatin, intellectual disability-severe speech delay-mild dysmorphism syndrome, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, DYRK1A-related intellectual disability syndrome, intellectual disability, autosomal dominant 13, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, CTCF-related neurodevelopmental disorder, Bosch-Boonstra-Schaaf optic atrophy syndrome, autism spectrum disorder due to AUTS2 deficiency, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, intellectual developmental disorder with dysmorphic facies and ptosis, intellectual disability, autosomal dominant 48, SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, SIN3A-related intellectual disability syndrome, intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, SATB2 associated disorder

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

7 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1186953	NM_198880.3(QRICH1):c.1149_1150del (p.Phe384fs)	QRICH1	Pathogenic	criteria provided, multiple submitters, no conflicts
4531899	NM_198880.3(QRICH1):c.697dup (p.Glu233fs)	QRICH1	Pathogenic	criteria provided, single submitter
4684983	NM_198880.3(QRICH1):c.1324C>T (p.Gln442Ter)	QRICH1	Pathogenic	criteria provided, single submitter
4819127	NM_198880.3(QRICH1):c.1671+1G>A	QRICH1	Pathogenic	criteria provided, single submitter
4846918	NM_198880.3(QRICH1):c.296del (p.Pro99fs)	QRICH1	Likely pathogenic	criteria provided, single submitter
1703943	NM_198880.3(QRICH1):c.2266C>T (p.Arg756Trp)	QRICH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4291912	NM_198880.3(QRICH1):c.1895+3_1895+6del	QRICH1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
QRICH1	Definitive	Autosomal dominant	Ververi-Brady syndrome 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
QRICH1	Orphanet:580940	QRICH1-related intellectual disability-chondrodysplasia syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
QRICH1	HGNC:24713	ENSG00000198218	Q2TAL8	Transcriptional regulator QRICH1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
QRICH1	Transcriptional regulator QRICH1	Transcriptional regulator that acts as a mediator of the integrated stress response (ISR) through transcriptional control of protein homeostasis under conditions of ER stress.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
QRICH1	Transcription factor	no		ZMYM2-like_C, ZnF_MYMT-QRICH1, QRICH1_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
skin of abdomen	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
QRICH1	293	ubiquitous	marker	granulocyte, skin of leg, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
QRICH1	3,350

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
QRICH1	Q2TAL8	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
PERK-mediated unfolded protein response	1	1872.4×	0.004	QRICH1
integrated stress response signaling	1	702.2×	0.005	QRICH1
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	1	481.5×	0.005	QRICH1
endoplasmic reticulum unfolded protein response	1	295.6×	0.006	QRICH1
response to endoplasmic reticulum stress	1	166.8×	0.008	QRICH1
positive regulation of apoptotic process	1	56.7×	0.021	QRICH1
positive regulation of DNA-templated transcription	1	27.9×	0.036	QRICH1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
QRICH1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	QRICH1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
QRICH1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.