QRICH1

Summary

QRICH1 (glutamine rich 1, HGNC:24713) is a protein-coding gene on chromosome 3p21.31, encoding Transcriptional regulator QRICH1 (Q2TAL8). Transcriptional regulator that acts as a mediator of the integrated stress response (ISR) through transcriptional control of protein homeostasis under conditions of ER stress. It is a selective cancer dependency (DepMap: 20.5% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

Enables DNA binding activity. Involved in intracellular signal transduction; positive regulation of DNA-templated transcription; and positive regulation of apoptotic process. Located in nucleus.

Source: NCBI Gene 54870 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 20
• Clinical variants (ClinVar): 249 total — 47 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 36
• Cancer dependency (DepMap): dependent in 20.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_198880

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24713
Approved symbol	QRICH1
Name	glutamine rich 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20259, VERBRAS, AB-DIP
Ensembl gene	ENSG00000198218
Ensembl biotype	protein_coding
OMIM	617387
Entrez	54870

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 32 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000357496, ENST00000395443, ENST00000411682, ENST00000424300, ENST00000430979, ENST00000437939, ENST00000450685, ENST00000469910, ENST00000477021, ENST00000479449, ENST00000489642, ENST00000498392, ENST00000498440, ENST00000703871, ENST00000703872, ENST00000703873, ENST00000703938, ENST00000703939, ENST00000703940, ENST00000703941, ENST00000703942, ENST00000703943, ENST00000887075, ENST00000887076, ENST00000887077, ENST00000887078, ENST00000887079, ENST00000887080, ENST00000887081, ENST00000887082, ENST00000887083, ENST00000887084, ENST00000887085, ENST00000939601, ENST00000939602, ENST00000939603, ENST00000939604, ENST00000939605, ENST00000939606, ENST00000939607, ENST00000939608, ENST00000939609, ENST00000971840, ENST00000971841, ENST00000971842

RefSeq mRNA: 8 — MANE Select: NM_198880 NM_001320580, NM_001320581, NM_001320582, NM_001320583, NM_001320584, NM_001320585, NM_017730, NM_198880

CCDS: CCDS2787

Canonical transcript exons

ENST00000395443 — 10 exons

Exon	Start	End
ENSE00001292887	49056862	49057890
ENSE00001309363	49029707	49030644
ENSE00001326142	49076709	49077038
ENSE00001330854	49033120	49033228
ENSE00001928432	49093912	49094071
ENSE00003487937	49032622	49032773
ENSE00003516779	49046425	49046579
ENSE00003539598	49044390	49044504
ENSE00003597309	49032183	49032273
ENSE00003648339	49047069	49047246

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.5567 / max 302.5122, expressed in 1824 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42206	37.3471	1817
42203	2.9094	1456
42205	1.8969	1234
42193	1.5909	1131
42195	1.4837	1035
42204	1.1191	653
42194	0.9589	556
42208	0.8251	543
42196	0.7085	424
42197	0.6864	301

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.15	gold quality
skin of leg	UBERON:0001511	96.13	gold quality
skin of abdomen	UBERON:0001416	96.10	gold quality
right testis	UBERON:0004534	95.83	gold quality
left testis	UBERON:0004533	95.69	gold quality
right lung	UBERON:0002167	95.67	gold quality
cortical plate	UBERON:0005343	95.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.38	gold quality
cerebellar hemisphere	UBERON:0002245	95.30	gold quality
ganglionic eminence	UBERON:0004023	95.26	gold quality
ventricular zone	UBERON:0003053	95.21	gold quality
cerebellar cortex	UBERON:0002129	95.15	gold quality
spleen	UBERON:0002106	95.12	gold quality
mucosa of stomach	UBERON:0001199	95.06	gold quality
testis	UBERON:0000473	95.00	gold quality
rectum	UBERON:0001052	94.83	gold quality
zone of skin	UBERON:0000014	94.81	gold quality
left uterine tube	UBERON:0001303	94.80	gold quality
lymph node	UBERON:0000029	94.77	gold quality
right uterine tube	UBERON:0001302	94.66	gold quality
body of uterus	UBERON:0009853	94.66	gold quality
right ovary	UBERON:0002118	94.65	gold quality
ectocervix	UBERON:0012249	94.61	gold quality
descending thoracic aorta	UBERON:0002345	94.58	gold quality
right lobe of thyroid gland	UBERON:0001119	94.56	gold quality
upper lobe of left lung	UBERON:0008952	94.54	gold quality
body of stomach	UBERON:0001161	94.49	gold quality
endocervix	UBERON:0000458	94.46	gold quality
left lobe of thyroid gland	UBERON:0001120	94.42	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.91
E-MTAB-6379	no	1092.70
E-MTAB-7606	no	812.11
E-GEOD-124858	no	221.31

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
EARS2	Activation
FARS2	Activation
FARSB	Activation
IARS1	Activation
TARS2	Activation
VARS1	Activation
VARS2	Activation
WARS2	Activation
YARS2	Activation

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

50 targeting QRICH1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-657	99.48	66.02	848
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-4731-3P	98.56	68.60	1860

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 20.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• Despite their small number, the patients had a relatively consistent pattern of clinical features suggesting the presence of a QRICH1-associated phenotype. LoF mutations in QRICH1 are suggested as a novel cause of developmental delay. (PMID:28692176)
• Our findings indicate that QRICH1 mutations cause not only developmental delay but also a chondrodysplasia characterized by diminished linear growth and abnormal growth plate morphology due to impaired growth plate chondrocyte hypertrophic differentiation. (PMID:30281152)
• QRICH1 variants in Ververi-Brady syndrome-delineation of the genotypic and phenotypic spectrum. (PMID:33009816)
• QRICH1 dictates the outcome of ER stress through transcriptional control of proteostasis. (PMID:33384352)
• A case of Ververi-Brady syndrome due to QRICH1 loss of function and the literature review. (PMID:33738978)
• QRICH1 suppresses pediatric T-cell acute lymphoblastic leukemia by inhibiting GRP78. (PMID:39227586)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	qrich1	ENSDARG00000019797
mus_musculus	Qrich1	ENSMUSG00000006673
rattus_norvegicus	Qrich1	ENSRNOG00000025071

Paralogs (18): GTF2IRD1 (ENSG00000006704), ZMYM2 (ENSG00000121741), ZMYM5 (ENSG00000132950), THAP12 (ENSG00000137492), ZMYM4 (ENSG00000146463), ZMYM3 (ENSG00000147130), ZMYM6 (ENSG00000163867), KIAA1958 (ENSG00000165185), GTF2IRD2B (ENSG00000174428), EPM2AIP1 (ENSG00000178567), GTF2IRD2 (ENSG00000196275), ZMYM1 (ENSG00000197056), FAM200C (ENSG00000221886), FAM200A (ENSG00000221909), SCAND3 (ENSG00000232040), ZBED5 (ENSG00000236287), FAM200B (ENSG00000237765), GTF2I (ENSG00000263001)

Protein

Protein identifiers

Transcriptional regulator QRICH1 — Q2TAL8 (reviewed: Q2TAL8)

Alternative names: Glutamine-rich protein 1

All UniProt accessions (11): A0A994J424, A0A994J457, A0A994J492, A0A994J4K3, A0A994J4P1, A0A994J6Q4, A0A994J751, A1L3Z9, C9JAL2, C9JIA8, Q2TAL8

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator that acts as a mediator of the integrated stress response (ISR) through transcriptional control of protein homeostasis under conditions of ER stress. Controls the outcome of the unfolded protein response (UPR) which is an ER-stress response pathway. ER stress induces QRICH1 translation by a ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced QRICH1 regulates a transcriptional program associated with protein translation, protein secretion-mediated proteotoxicity and cell death during the terminal UPR. May cooperate with ATF4 transcription factor signaling to regulate ER homeostasis which is critical for cell viability. Up-regulates CASP3/caspase-3 activity in epithelial cells under ER stress. Central regulator of proteotoxicity associated with ER stress-mediated inflammatory diseases in the intestines and liver. Core component of the zincore complex, a heterotetramer that acts as a molecular ‘grip’ to stabilize transcription factors at DNA-binding sites across the genome, thereby controlling gene expression. The zincore complex binds specifically to zinc finger transcription factors, such as ZFP91, ZNF652, ZNF526 and PRDM15, and stabilizes them onto their cognate DNA motif. Involved in chondrocyte hypertrophy, a process required for normal longitudinal bone growth.

Subunit / interactions. Component of the zincore complex, a heterotetramer composed of a dimer of QRICH1 and SEPHS1.

Subcellular location. Nucleus. Chromosome. Cytoplasm. Cell membrane.

Disease relevance. Ververi-Brady syndrome 1 (VERBRAS1) [MIM:617982] An autosomal dominant disorder characterized by mild developmental delay and intellectual disability, speech delay, learning difficulties, autistic features, and mild facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The CARD domain may be involved in the regulation of caspase activity in the context of programmed cell death.

Induction. Regulated at the translational level via an alternative ribosome re-initiation mechanism in response to various stress such as endoplasmic reticulum stress or oxidative stress. In the absence of stress, ribosomes re-initiate translation at an inhibitory upstream open reading frames (uORFs) of the QRICH1 transcript, which preclude QRICH1 translation. In response to stress and subsequent EIF2S1/eIF-2-alpha phosphorylation, ribosomes bypass the inhibitory uORFs and re-initiate translation at the QRICH1 coding sequence. Positive autoregulation at the transcriptional level.

RefSeq proteins (8): NP_001307509, NP_001307510, NP_001307511, NP_001307512, NP_001307513, NP_001307514, NP_060200, NP_942581* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021893	ZMYM2-like_C	Domain
IPR051284	ZnF_MYMT-QRICH1	Family
IPR057926	QRICH1_dom	Domain

Pfam: PF12012, PF25561

UniProt features (32 total): sequence variant 20, region of interest 3, modified residue 3, cross-link 2, chain 1, domain 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9HJU	ELECTRON MICROSCOPY	3.16
9HJT	ELECTRON MICROSCOPY	3.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2TAL8-F1	58.67	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 358, 1, 345, 464, 353

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 260 (showing top): RNGTGGGC_UNKNOWN, CMYB_01, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, EFC_Q6, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_ER_NUCLEUS_SIGNALING_PATHWAY, FREAC3_01, GOBP_APOPTOTIC_SIGNALING_PATHWAY, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, HFH3_01, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, HTF_01, HIF1_Q3, COATES_MACROPHAGE_M1_VS_M2_DN

GO Biological Process (9): endoplasmic reticulum unfolded protein response (GO:0030968), response to endoplasmic reticulum stress (GO:0034976), PERK-mediated unfolded protein response (GO:0036499), positive regulation of apoptotic process (GO:0043065), positive regulation of DNA-templated transcription (GO:0045893), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), integrated stress response signaling (GO:0140467), response to unfolded protein (GO:0006986), regulation of apoptotic process (GO:0042981)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	2
cellular response to stress	2
apoptotic process	2
cellular anatomical structure	2
cellular response to unfolded protein	1
intracellular signal transduction	1
ER-nucleus signaling pathway	1
endoplasmic reticulum unfolded protein response	1
integrated stress response signaling	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
intrinsic apoptotic signaling pathway	1
intracellular signaling cassette	1
response to topologically incorrect protein	1
regulation of programmed cell death	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2888 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
QRICH1	QRICH2	Q9H0J4	734
QRICH1	GIGYF2	Q6Y7W6	563
QRICH1	TSSK4	Q6SA08	560
QRICH1	HARBI1	Q96MB7	548
QRICH1	MARCHF10	Q8NA82	510
QRICH1	PGBD5	Q8N414	508
QRICH1	B3GNT9	Q6UX72	506
QRICH1	CABYR	O75952	496
QRICH1	HHATL	Q9HCP6	477
QRICH1	TEKT4	Q8WW24	476
QRICH1	CFAP44	Q96MT7	474
QRICH1	ROPN1	Q9HAT0	470
QRICH1	SPATA6	Q9NWH7	456
QRICH1	AMTN	Q6UX39	455
QRICH1	GRAMD4	Q6IC98	452

IntAct

274 interactions, top by confidence:

A	B	Type	Score
QRICH1	SEPHS1	psi-mi:“MI:0915”(physical association)	0.780
QRICH1	FHL3	psi-mi:“MI:0915”(physical association)	0.780
QRICH1	HSPB8	psi-mi:“MI:0915”(physical association)	0.780
FHL3	QRICH1	psi-mi:“MI:0915”(physical association)	0.780
SEPHS1	QRICH1	psi-mi:“MI:0915”(physical association)	0.780
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
QRICH1	CRX	psi-mi:“MI:0915”(physical association)	0.720
QRICH1	TRAF1	psi-mi:“MI:0915”(physical association)	0.720
TRAF1	QRICH1	psi-mi:“MI:0915”(physical association)	0.720
CRX	QRICH1	psi-mi:“MI:0915”(physical association)	0.720
QRICH1	POGZ	psi-mi:“MI:0915”(physical association)	0.700
QRICH1	GMCL1	psi-mi:“MI:0915”(physical association)	0.700
POGZ	QRICH1	psi-mi:“MI:0915”(physical association)	0.700
RBM17	QRICH1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (188): QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), QRICH1 (Two-hybrid), GMCL1 (Two-hybrid), RBM17 (Two-hybrid), HSFY1 (Two-hybrid), QRICH1 (Affinity Capture-RNA)

ESM2 similar proteins: A1L2U9, A2BID7, B1WAZ8, B4F6U4, E9Q8T2, F1QLG5, H2L008, O08785, O15164, P57071, P70121, Q05516, Q08BR4, Q0IH98, Q0P5J0, Q0VCJ6, Q2M1K9, Q2TAL8, Q3U288, Q3UA37, Q3UTQ7, Q53TQ3, Q56R14, Q5NBY9, Q5RAX9, Q5RGA4, Q5XJV7, Q64127, Q6E2N3, Q6INA9, Q6YND2, Q7Z3K3, Q8BZH4, Q8K0L9, Q8N1W2, Q8QGQ6, Q8R515, Q91YB0, Q91YB2, Q96BR9

Diamond homologs: A2A791, A6QPH9, O95789, Q0P5J0, Q14202, Q2TAL8, Q3U2E2, Q3UA37, Q4R3D6, Q5RDJ2, Q5SVZ6, Q5VZL5, Q9CU65, Q9JLM4, Q9UBW7, Q9UJ78

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
“ER stress”	up-regulates	QRICH1
QRICH1	up-regulates	Cell_death
QRICH1	“up-regulates quantity by expression”	EARS2	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	FARS2	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	FARSB	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	GARS1	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	IARS1	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	TARS2	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	VARS1	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	VARS2	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	WARS1	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	WARS2	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	YARS1	“transcriptional regulation”
QRICH1	“up-regulates quantity by expression”	YARS2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

249 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	26
Uncertain significance	142
Likely benign	15
Benign	2

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1186953	NM_198880.3(QRICH1):c.1149_1150del (p.Phe384fs)	Pathogenic
1192535	NM_198880.3(QRICH1):c.1585dup (p.Cys529fs)	Pathogenic
1329908	NM_198880.3(QRICH1):c.46C>T (p.Arg16Ter)	Pathogenic
1329909	NM_198880.3(QRICH1):c.136del (p.Gln46fs)	Pathogenic
1329911	NM_198880.3(QRICH1):c.541C>T (p.Gln181Ter)	Pathogenic
1329913	NM_198880.3(QRICH1):c.823C>T (p.Gln275Ter)	Pathogenic
1329915	NM_198880.3(QRICH1):c.985del (p.His329fs)	Pathogenic
1329917	NM_198880.3(QRICH1):c.1258C>T (p.Gln420Ter)	Pathogenic
1329918	NM_198880.3(QRICH1):c.1292dup (p.Pro432fs)	Pathogenic
1329921	NM_198880.3(QRICH1):c.1531C>T (p.Arg511Ter)	Pathogenic
1329923	NM_198880.3(QRICH1):c.1626del (p.Tyr543fs)	Pathogenic
1329927	NM_198880.3(QRICH1):c.1787-2A>G	Pathogenic
1329930	NM_198880.3(QRICH1):c.1896-2A>G	Pathogenic
1701965	NM_198880.3(QRICH1):c.418del (p.Gln140fs)	Pathogenic
2008780	NM_198880.3(QRICH1):c.1315C>T (p.Gln439Ter)	Pathogenic
2024521	NM_198880.3(QRICH1):c.486dup (p.Gln163fs)	Pathogenic
2218827	NM_198880.3(QRICH1):c.259C>T (p.Gln87Ter)	Pathogenic
2356055	NM_198880.3(QRICH1):c.325C>T (p.Gln109Ter)	Pathogenic
2525239	NM_198880.3(QRICH1):c.400C>T (p.Gln134Ter)	Pathogenic
2603789	NM_198880.3(QRICH1):c.1828G>T (p.Glu610Ter)	Pathogenic
2674595	NM_198880.3(QRICH1):c.845dup (p.Leu282fs)	Pathogenic
3254774	NM_198880.3(QRICH1):c.949dup (p.Gln317fs)	Pathogenic
3337504	NM_198880.3(QRICH1):c.1337C>G (p.Ser446Ter)	Pathogenic
3389600	NM_198880.3(QRICH1):c.1453_1454del (p.Trp485fs)	Pathogenic
3390657	NM_198880.3(QRICH1):c.532C>T (p.Gln178Ter)	Pathogenic
3428869	NM_198880.3(QRICH1):c.3G>A (p.Met1Ile)	Pathogenic
3428870	NM_198880.3(QRICH1):c.1345dup (p.Thr449fs)	Pathogenic
3764092	NM_198880.3(QRICH1):c.1346_1351delinsGT (p.Thr449fs)	Pathogenic
3766301	NM_198880.3(QRICH1):c.630del (p.Ile211fs)	Pathogenic
3897868	NM_198880.3(QRICH1):c.337dup (p.Gln113fs)	Pathogenic

SpliceAI

2444 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49032618:CTAC:C	donor_loss	1.0000
3:49032620:A:AT	donor_loss	1.0000
3:49032621:CCT:C	donor_loss	1.0000
3:49032621:CCTTT:C	donor_gain	1.0000
3:49044383:CTCTT:C	donor_loss	1.0000
3:49044384:TCTTA:T	donor_loss	1.0000
3:49044385:CTTAC:C	donor_loss	1.0000
3:49044386:TTA:T	donor_loss	1.0000
3:49044387:TACC:T	donor_loss	1.0000
3:49044388:A:AC	donor_gain	1.0000
3:49044388:ACC:A	donor_loss	1.0000
3:49044389:C:CC	donor_gain	1.0000
3:49044389:C:G	donor_loss	1.0000
3:49044500:AGATA:A	acceptor_gain	1.0000
3:49044501:GATA:G	acceptor_gain	1.0000
3:49044502:ATA:A	acceptor_gain	1.0000
3:49044503:TA:T	acceptor_gain	1.0000
3:49044504:AC:A	acceptor_loss	1.0000
3:49044505:C:CC	acceptor_gain	1.0000
3:49044505:C:T	acceptor_loss	1.0000
3:49044506:T:G	acceptor_loss	1.0000
3:49046419:TCCTA:T	donor_loss	1.0000
3:49046420:CCTA:C	donor_loss	1.0000
3:49046421:CTACC:C	donor_loss	1.0000
3:49046422:TA:T	donor_loss	1.0000
3:49046423:ACCT:A	donor_loss	1.0000
3:49046424:C:CG	donor_loss	1.0000
3:49047067:A:AC	donor_gain	1.0000
3:49047067:ACT:A	donor_gain	1.0000
3:49047067:ACTC:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000069161 (3:49080791 T>C), RS1000107605 (3:49083732 C>T), RS1000126447 (3:49088057 G>T), RS1000213530 (3:49069269 C>G,T), RS1000225119 (3:49038856 G>A), RS1000240148 (3:49046005 TC>T), RS1000240751 (3:49045029 G>A), RS1000400070 (3:49032826 T>C), RS1000406267 (3:49044741 G>A), RS1000427163 (3:49075863 A>T), RS1000460709 (3:49033508 C>T), RS1000476152 (3:49094249 C>G), RS1000500141 (3:49079221 G>A,C), RS1000515274 (3:49092029 A>C), RS1000559651 (3:49058497 T>C)

Disease associations

OMIM: gene MIM:617387 | disease phenotypes: MIM:617982

GenCC curated gene-disease

Disease	Classification	Inheritance
Ververi-Brady syndrome 1	Definitive	Autosomal dominant
schizophrenia	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (5): Ververi-Brady syndrome (MONDO:0979877), intellectual disability (MONDO:0001071), Ververi-Brady syndrome 1 (MONDO:0060707), autism spectrum disorder (MONDO:0005258), schizophrenia (MONDO:0005090)

Orphanet (3): QRICH1-related intellectual disability-chondrodysplasia syndrome (Orphanet:580940), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000445	Wide nose
HP:0000448	Prominent nose
HP:0000455	Broad nasal tip
HP:0000508	Ptosis
HP:0000582	Upslanted palpebral fissure
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001195	Single umbilical artery
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001511	Intrauterine growth retardation
HP:0001669	Transposition of the great arteries
HP:0002080	Intention tremor
HP:0002317	Unsteady gait
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST003818_48	Resting heart rate	3.000000e-13
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005194_129	Coronary artery disease	6.000000e-09
GCST007294_107	Body fat distribution (trunk fat ratio)	9.000000e-06
GCST007294_72	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007294_98	Body fat distribution (trunk fat ratio)	3.000000e-15
GCST007295_21	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_45	Body fat distribution (leg fat ratio)	1.000000e-10
GCST007295_80	Body fat distribution (leg fat ratio)	1.000000e-14
GCST007709_13	General factor of neuroticism	4.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST012490_121	Femur bone mineral density x serum urate levels interaction	1.000000e-08
GCST90020029_1176	Waist circumference adjusted for body mass index	3.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0007660	neuroticism measurement
EFO:0004346	neuroimaging measurement
EFO:0004531	urate measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4974081	QRICH1		0.00	0

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
trichostatin A	affects expression	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Diazinon	increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Vinblastine	increases phosphorylation	1
Vincristine	increases phosphorylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Nocodazole	decreases reaction, increases phosphorylation	1
Aflatoxin B1	increases methylation	1
Paclitaxel	increases phosphorylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Genistein	decreases reaction, increases phosphorylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2CY	Abcam HeLa QRICH1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

599 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety