QRICH1

Chr 3

glutamine rich 1

Also known as: AB-DIP, VERBRAS, VERBRAS1

NCBI Gene: 54870 ENSG00000198218 UniProt: Q2TAL8

The QRICH1 protein binds DNA and functions as a transcriptional activator while also promoting apoptosis through intracellular signaling pathways. Loss-of-function mutations cause Ververi-Brady syndrome 1, an autosomal dominant neurodevelopmental disorder. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Enables DNA binding activity. Involved in intracellular signal transduction; positive regulation of DNA-templated transcription; and positive regulation of apoptotic process. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

Clinical Summary— QRICH1

🧬

Gene-Disease Validity (ClinGen)

syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

75 unique Pathogenic / Likely Pathogenic· 142 VUS of 250 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.28LOEUF

pLI 0.996

Z-score 4.98

OE 0.13 (0.07–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.71Z-score

OE missense 0.49 (0.44–0.55)

211 obs / 426.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.28)

0≤0.351.4

Missense OE?0.49 (0.44–0.55)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 5 / 38.2Missense obs/exp: 211 / 426.7Syn Z: -0.47

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveQRICH1-related syndromeLOFAD

This gene — mechanism propensity

0.2499th %ile

GOF

0.2597th %ile

LOF

0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 81% of P/LP variants are LoF · LOEUF 0.28 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFThese findings suggest that haploinsufficiency of QRICH1 could affect multiple organ systems, including brain and bone.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 30281152 ↗

ClinVar Variant Classifications

250 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47

Likely Pathogenic28

VUS142

Likely Benign16

Benign2

Conflicting5

Pathogenic

Likely Pathogenic

142

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	45	1	1	0	47
Likely Pathogenic	16	10	2	0	28
VUS	7	131	3	1	142
Likely Benign	0	1	1	14	16
Benign	0	1	0	1	2
Conflicting	—				5
Total	68	144	7	16	240

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap QRICH1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →