CRYZ

Summary

CRYZ (crystallin zeta, HGNC:2419) is a protein-coding gene on chromosome 1p31.1, encoding Zeta-crystallin (Q08257). Multifunctional crystallin endowed with unrelated mRNA stabilization and enzymatic oxidoreductase activities.

Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. The former class is also called phylogenetically-restricted crystallins. This gene encodes a taxon-specific crystallin protein which has NADPH-dependent quinone reductase activity distinct from other known quinone reductases. It lacks alcohol dehydrogenase activity although by similarity it is considered a member of the zinc-containing alcohol dehydrogenase family. Unlike other mammalian species, in humans, lens expression is low. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. One pseudogene is known to exist.

Source: NCBI Gene 1429 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 71 total
• Druggable target: yes
• MANE Select transcript: NM_001889

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2419
Approved symbol	CRYZ
Name	crystallin zeta
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116791
Ensembl biotype	protein_coding
OMIM	123691
Entrez	1429

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 48 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000340866, ENST00000370870, ENST00000370871, ENST00000370872, ENST00000441120, ENST00000492102, ENST00000888604, ENST00000888605, ENST00000888606, ENST00000888607, ENST00000888608, ENST00000888609, ENST00000888610, ENST00000888611, ENST00000888612, ENST00000888613, ENST00000888614, ENST00000888615, ENST00000888616, ENST00000888617, ENST00000888618, ENST00000888619, ENST00000888620, ENST00000888621, ENST00000888622, ENST00000888623, ENST00000888624, ENST00000888625, ENST00000888626, ENST00000888627, ENST00000888628, ENST00000888629, ENST00000888630, ENST00000888631, ENST00000888632, ENST00000888633, ENST00000888634, ENST00000888635, ENST00000888636, ENST00000888637, ENST00000888638, ENST00000888639, ENST00000888640, ENST00000888641, ENST00000888642, ENST00000888643, ENST00000931362, ENST00000931363, ENST00000944856

RefSeq mRNA: 4 — MANE Select: NM_001889 NM_001130042, NM_001130043, NM_001134759, NM_001889

CCDS: CCDS44162, CCDS44163, CCDS665

Canonical transcript exons

ENST00000340866 — 9 exons

Exon	Start	End
ENSE00000774937	74706899	74706994
ENSE00000774938	74707103	74707204
ENSE00000774939	74710098	74710247
ENSE00000774940	74714579	74714630
ENSE00000956978	74719209	74719372
ENSE00001312257	74724711	74724834
ENSE00001908982	74732956	74733050
ENSE00001927007	74705486	74706457
ENSE00003478858	74723118	74723270

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3253 / max 376.7165, expressed in 1652 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12864	17.8821	1647
12865	0.3690	181
12863	0.0397	8
12862	0.0346	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.18	gold quality
renal medulla	UBERON:0000362	98.81	gold quality
oocyte	CL:0000023	98.66	gold quality
nephron tubule	UBERON:0001231	98.66	gold quality
adult mammalian kidney	UBERON:0000082	98.24	gold quality
kidney	UBERON:0002113	97.60	gold quality
right lobe of liver	UBERON:0001114	97.55	gold quality
corpus epididymis	UBERON:0004359	97.46	gold quality
kidney epithelium	UBERON:0004819	97.42	gold quality
caput epididymis	UBERON:0004358	97.41	gold quality
liver	UBERON:0002107	97.37	gold quality
metanephros cortex	UBERON:0010533	97.36	gold quality
seminal vesicle	UBERON:0000998	97.17	gold quality
body of pancreas	UBERON:0001150	97.12	gold quality
gall bladder	UBERON:0002110	97.12	gold quality
jejunal mucosa	UBERON:0000399	96.91	gold quality
islet of Langerhans	UBERON:0000006	96.84	gold quality
pancreas	UBERON:0001264	96.49	gold quality
cortex of kidney	UBERON:0001225	96.37	gold quality
choroid plexus epithelium	UBERON:0003911	96.26	gold quality
renal glomerulus	UBERON:0000074	96.20	gold quality
metanephric glomerulus	UBERON:0004736	96.15	gold quality
duodenum	UBERON:0002114	96.03	gold quality
metanephros	UBERON:0000081	95.82	gold quality
adult organism	UBERON:0007023	94.93	gold quality
cauda epididymis	UBERON:0004360	94.67	gold quality
calcaneal tendon	UBERON:0003701	94.63	gold quality
right uterine tube	UBERON:0001302	94.24	gold quality
endometrium	UBERON:0001295	94.12	gold quality
pigmented layer of retina	UBERON:0001782	94.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	8.80
E-CURD-135	no	547.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2, MAFG, MAFK, NFE2L2, NRL, PAX6, TCF3

miRNA regulators (miRDB)

51 targeting CRYZ, 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-340-5P	100.00	72.50	4437
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-8064	99.45	66.92	875

Literature-anchored findings (GeneRIF, showing 6)

• up-regulation of quinone reductase can protect breast cells against oxidative DNA damage (PMID:12714703)
• zeta-Crystallin is a bcl-2 mRNA binding protein involved in bcl-2 overexpression in T-cell acute lymphocytic leukemia. (PMID:20103721)
• novel enzymatic activity for human zeta-crystallin, the double- bond a,b-hydrogenation of 2-alkenals and 3-alkenones, was identified. (PMID:20835842)
• role of Zta1p in the yeast adaptation to some stress types and the general functional significance of zeta-crystallins (PMID:21276778)
• Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels (PMID:22843503)
• Zeta-crystallin is a moonlighting protein endowed with two main different functions: (1) mRNA binding with stabilizing activity; (2) NADPH:quinone oxidoreductase. Zeta-crystallin has been clearly demonstrated to stabilize mRNAs encoding proteins involved in renal glutamine catabolism during metabolic acidosis resulting in ammoniagenesis and bicarbonate ion production that concur to compensate such condition. [review] (PMID:31563996)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cryz	ENSDARG00000016074
mus_musculus	Cryz	ENSMUSG00000028199
rattus_norvegicus	Cryz	ENSRNOG00000028319
caenorhabditis_elegans	F39B2.3	WBGENE00009554

Paralogs (17): PTGR1 (ENSG00000106853), VAT1 (ENSG00000108828), TP53I3 (ENSG00000115129), MECR (ENSG00000116353), RTN4IP1 (ENSG00000130347), PTGR2 (ENSG00000140043), SORD (ENSG00000140263), VAT1L (ENSG00000171724), ADH6 (ENSG00000172955), PTGR3 (ENSG00000180011), ADH1A (ENSG00000187758), ADH7 (ENSG00000196344), ADH1B (ENSG00000196616), ADH5 (ENSG00000197894), ADH4 (ENSG00000198099), CRYZL1 (ENSG00000205758), ADH1C (ENSG00000248144)

Protein

Protein identifiers

Zeta-crystallin — Q08257 (reviewed: Q08257)

Alternative names: NADPH:quinone reductase

All UniProt accessions (3): Q08257, A6NP24, C9JH92

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional crystallin endowed with unrelated mRNA stabilization and enzymatic oxidoreductase activities. Binds (AU)-rich elements (ARE) in the 3’-UTR of target mRNA to enhance their stability. Upon metabolic acidosis, stabilizes the mRNA encoding SLC12A1 a cotransporter involved in transepithelial NH4(+) reabsorption in the medullary thick ascending limb in kidney. In response to acidosis, also participates to the adaptive increase in renal ammoniagenesis by stabilizing the mRNAs of enzymes involved in glutamine catabolism. By the same mechanism, it also regulates the expression of the antiapoptotic protein BCL2. Beside its mRNA stabilization activity, also catalyzes the reduction of orthoquinones such as 1,2-naphthoquinone or 9,10-phenanthrenequinone in the presence of NADPH in vitro and could be involved in the detoxification of xenobiotics and protection against oxidative stress.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Only very low amounts in the lens.

Similarity. Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q08257-1	1	yes
Q08257-2	2
Q08257-3	3

RefSeq proteins (4): NP_001123514, NP_001123515, NP_001128231, NP_001880* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002364	Quin_OxRdtase/zeta-crystal_CS	Conserved_site
IPR011032	GroES-like_sf	Homologous_superfamily
IPR013149	ADH-like_C	Domain
IPR013154	ADH-like_N	Domain
IPR020843	ER	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR051603	Zinc-ADH_QOR/CCCR	Family

Pfam: PF00107, PF08240

Enzyme classification (BRENDA):

• EC 1.3.1.27 — 2-hexadecenal reductase (BRENDA: 6 organisms, 32 substrates, 5 inhibitors, 15 Km, 4 kcat entries)
• EC 1.6.5.5 — NADPH:quinone reductase (BRENDA: 18 organisms, 97 substrates, 43 inhibitors, 93 Km, 80 kcat entries)

Substrate kinetics (BRENDA)

56 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.0025–0.07	13
9,10-PHENANTHRENEQUINONE	0.0006–0.0491	9
1,4-BENZOQUINONE	0.011–0.37	6
5-HYDROXY-1,4-NAPHTHOQUINONE	0.0016–0.074	5
4-HYDROXY-2-HEXENAL	0.13–3.67	3
NADPH	0.005–0.06	3
1,2-NAPHTHOQUINONE	0.0024–0.029	3
1,4-NAPHTHOQUINONE	0.033–0.26	3
2-HEXENAL	0.13–6.12	3
3-BUTEN-2-ONE	0.035–0.13	3
4-HYDROXY-2-HEXENAL	0.08–1.26	3
PROPENAL	0.86–2.3	3
2-HYDROXY-1,4-NAPHTHOQUINONE	0.0066–0.0237	2
2-METHYL-1,4-NAPHTHOQUINONE	0.13–0.23	2
3-NONEN-2-ONE	0.05–0.94	2

Catalyzed reactions (Rhea), 3 shown:

• 2 a quinone + NADPH + H(+) = 2 a 1,4-benzosemiquinone + NADP(+) (RHEA:14269)
• 2 1,2-naphthoquinone + NADPH + H(+) = 2 1,2-naphthosemiquinone + NADP(+) (RHEA:85243)
• 2 9,10-phenanthroquinone + NADPH + H(+) = 2 9,10-phenanthrosemiquinone + NADP(+) (RHEA:85247)

UniProt features (60 total): strand 17, binding site 14, helix 14, modified residue 4, splice variant 3, sequence variant 3, turn 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1YB5	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08257-F1	96.95	0.97

Functional residue map

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

Ligand- & substrate-binding residues (14): 229; 246; 249; 269; 271; 321; 53; 158; 159; 160; 161; 181 …

Post-translational modifications (4): 2, 23, 248, 296

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 198 (showing top): MODULE_93, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, MCLACHLAN_DENTAL_CARIES_DN, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GARY_CD5_TARGETS_DN, BIOCARTA_ARENRF2_PATHWAY, MODULE_88

GO Biological Process (3): visual perception (GO:0007601), xenobiotic catabolic process (GO:0042178), protein homotetramerization (GO:0051289)

GO Molecular Function (8): mRNA 3’-UTR binding (GO:0003730), quinone reductase (NADPH) activity (GO:0003960), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), NADPH binding (GO:0070402), RNA binding (GO:0003723), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
sensory perception of light stimulus	1
xenobiotic metabolic process	1
catabolic process	1
protein homooligomerization	1
protein tetramerization	1
mRNA binding	1
NADPH dehydrogenase activity	1
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	1
transition metal ion binding	1
protein binding	1
anion binding	1
NADP binding	1
nucleic acid binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYZ	NQO1	P15559	910
CRYZ	HMOX1	P09601	882
CRYZ	NFE2L2	Q16236	814
CRYZ	KEAP1	Q14145	788
CRYZ	GCLC	P48506	742
CRYZ	GCLM	P48507	711
CRYZ	GPX2	P18283	663
CRYZ	GPX8	Q8TED1	661
CRYZ	GPX7	Q96SL4	658
CRYZ	GPX5	O75715	655
CRYZ	GPX6	P59796	652
CRYZ	NQO2	P16083	645
CRYZ	DHX9	Q08211	639
CRYZ	TP53	P04637	637
CRYZ	SQOR	Q9Y6N5	636

IntAct

42 interactions, top by confidence:

A	B	Type	Score
CRYZ	CRYZ	psi-mi:“MI:0915”(physical association)	0.560
CRYZ	MMUT	psi-mi:“MI:0914”(association)	0.560
CRYZ	MMUT	psi-mi:“MI:0915”(physical association)	0.560
CBX5	KPNA3	psi-mi:“MI:0914”(association)	0.530
RPL4	CRYZ	psi-mi:“MI:0915”(physical association)	0.400
CSNK2A2	WDR46	psi-mi:“MI:0914”(association)	0.350
Mad2l1bp	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
ZNF526	VAMP4	psi-mi:“MI:0914”(association)	0.350
ASPM		psi-mi:“MI:0914”(association)	0.350
Ppp6r1	PPP6C	psi-mi:“MI:0914”(association)	0.350
Ppp4r3a	TIA1	psi-mi:“MI:0914”(association)	0.350
Cul3		psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
TRIP13	METTL8	psi-mi:“MI:0914”(association)	0.350
	NUDT19	psi-mi:“MI:0914”(association)	0.350
KDR	CALM1	psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DNASE2	C1QL1	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
FGG	ACOT7	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
OSBPL11	DNM1L	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
RBPMS	CA2	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (186): CAB39 (Co-fractionation), CRYZ (Co-fractionation), CRYZ (Co-fractionation), CRYZ (Co-fractionation), DCXR (Co-fractionation), LGALS3 (Co-fractionation), NNMT (Co-fractionation), SMAP2 (Co-fractionation), CRYZ (Affinity Capture-MS), CRYZ (Affinity Capture-MS), CRYZ (Affinity Capture-MS), CRYZ (Affinity Capture-MS), CRYZ (Affinity Capture-MS), CRYZ (Affinity Capture-MS), CRYZ (Affinity Capture-MS)

ESM2 similar proteins: A0A6N3IN21, A3KCL7, A6QQF5, B0BNC9, O35678, O75911, O77769, O88876, O97764, P00333, P05336, P11415, P14673, P14674, P14675, P17648, P28032, P47199, P50336, Q08257, Q0MVN8, Q0P5F9, Q28452, Q28GQ2, Q2R8Z5, Q3MIE4, Q3UGR5, Q3UNZ8, Q5BJJ5, Q5R4B4, Q5R4S7, Q60HD5, Q62465, Q6AYR6, Q6AYT0, Q75ZX4, Q80TB8, Q8LEB2, Q8R1Q9, Q8R238

Diamond homologs: A0A089FS99, A0A0C6DWS6, A0A0E0RXA7, A0A0E3U2K2, A0A0E4FKF7, A0A0F7GFI5, A0A0F9XJT1, A0A0L1JEX1, A0A1L7TY28, A0A1P8VF85, A0A1V6PAP3, A0A1W5T1Y4, A0A2L0P0L5, A0A2Z5XAK4, A0A3Q9U4Z5, A0A411KUQ4, A0A411KZZ8, A0A481WQL4, A0A482N9T9, A0A4P8W733, A0A6F8RQ72, A0A7L8UWS6, A0A7L9EZZ4, A0A8F4NUY3, A0A8F4S717, A0A8K1AWG4, A0JJU0, A1CLZ2, A2QQU5, A2QTF1, B1GVX6, B8NJH1, D7UPN2, G0REX7, G2Q9A7, G3JUI7, G3XMC6, G4MVZ3, G4MWB1, J5JCC9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1244 predictions. Top by Δscore:

Variant	Effect	Δscore
1:74706453:TCCTC:T	acceptor_gain	1.0000
1:74706454:CCTCC:C	acceptor_gain	1.0000
1:74706455:CTC:C	acceptor_gain	1.0000
1:74706458:C:CC	acceptor_gain	1.0000
1:74706888:T:TA	donor_gain	1.0000
1:74706895:CTA:C	donor_loss	1.0000
1:74706896:TACC:T	donor_loss	1.0000
1:74706897:ACCTT:A	donor_loss	1.0000
1:74706898:C:CA	donor_loss	1.0000
1:74706991:CAAC:C	acceptor_gain	1.0000
1:74707000:A:C	acceptor_gain	1.0000
1:74707200:TACTT:T	acceptor_gain	1.0000
1:74707201:ACTTC:A	acceptor_loss	1.0000
1:74707202:CTT:C	acceptor_gain	1.0000
1:74707202:CTTCT:C	acceptor_loss	1.0000
1:74707203:TTCTA:T	acceptor_loss	1.0000
1:74707204:TCTA:T	acceptor_loss	1.0000
1:74707205:C:CA	acceptor_loss	1.0000
1:74707205:C:CC	acceptor_gain	1.0000
1:74707207:A:C	acceptor_gain	1.0000
1:74710094:TTA:T	donor_loss	1.0000
1:74710095:TAC:T	donor_loss	1.0000
1:74710096:ACC:A	donor_loss	1.0000
1:74710097:C:CA	donor_loss	1.0000
1:74710123:T:TA	donor_gain	1.0000
1:74710243:CCAAC:C	acceptor_gain	1.0000
1:74710244:CAAC:C	acceptor_gain	1.0000
1:74710244:CAACC:C	acceptor_gain	1.0000
1:74710246:AC:A	acceptor_gain	1.0000
1:74710246:ACC:A	acceptor_loss	1.0000

AlphaMissense

2125 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:74723218:C:G	R55P	0.992
1:74723238:G:C	N48K	0.992
1:74723238:G:T	N48K	0.992
1:74714604:A:T	V152D	0.991
1:74723158:C:T	G75E	0.991
1:74723162:C:G	A74P	0.991
1:74723173:C:T	G70D	0.991
1:74719327:C:G	A104P	0.990
1:74707110:C:G	R242P	0.989
1:74714598:A:T	V154D	0.989
1:74719230:G:T	A136D	0.989
1:74723159:C:A	G75W	0.989
1:74706924:C:T	G268E	0.988
1:74710195:C:T	G178D	0.988
1:74719224:C:G	R138P	0.988
1:74723230:T:A	E51V	0.988
1:74706990:A:T	V246D	0.987
1:74706930:A:T	I266K	0.986
1:74707167:T:A	E223V	0.986
1:74714585:A:C	S158R	0.986
1:74714585:A:T	S158R	0.986
1:74714587:T:G	S158R	0.986
1:74714601:A:G	L153P	0.986
1:74706993:A:T	V245D	0.985
1:74714592:C:T	G156E	0.985
1:74719359:A:T	V93D	0.985
1:74723219:G:T	R55S	0.985
1:74710189:G:T	A180D	0.984
1:74714589:G:T	A157E	0.984
1:74723174:C:G	G70R	0.984

dbSNP variants (sampled 300 via entrez): RS1000003158 (1:74720748 T>C), RS1000020611 (1:74704986 C>T), RS1000022571 (1:74732099 G>T), RS1000149688 (1:74712332 C>G,T), RS1000283234 (1:74729280 C>T), RS1000409719 (1:74729803 G>C,T), RS1000438124 (1:74712105 A>C), RS1000633174 (1:74710872 A>C), RS1000657396 (1:74723528 T>C), RS1000717276 (1:74717382 C>A), RS1000835727 (1:74725166 T>A), RS1000895818 (1:74719089 A>G,T), RS1001206697 (1:74733889 G>A,T), RS1001539855 (1:74724877 G>A,T), RS1001569208 (1:74715637 A>T)

Disease associations

OMIM: gene MIM:123691 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001620_2	Resistin levels	6.000000e-12
GCST004158_3	Self-reported tiredness	6.000000e-08
GCST005950_6	Body mass index x sex x age interaction (4df test)	1.000000e-15
GCST005951_197	Body mass index	4.000000e-13
GCST005953_11	Body mass index (age <50)	3.000000e-15
GCST005954_3	Body mass index x age interaction	3.000000e-06
GCST006585_378	Blood protein levels	3.000000e-292
GCST006940_96	Neurociticism	8.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004819	resistin measurement
EFO:0007946	tiredness measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007660	neuroticism measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6118 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.07	IC50	8440	nM	CHEMBL4214264

PubChem BioAssay actives

1 with measured affinity, of 9 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]piperazin-1-yl]prop-2-en-1-one	1716422: Covalent binding affinity to CRYZ at Cys45 residue in human NCI-H358 cells assessed as reduction of log2 H/L ratio for tryptic peptide VHACGVNPVETYIR incubated for 4 hrs followed by cell lysis and subsequently labelled with light thiol probe N-((S)-18-iodo-11-isopropyl-10,13,17-trioxo-3,6-dioxa-9,12,16-triazaoctadecyl)-6-((4R,5S)-5-methyl-2-oxoimidazolidin-4-yl)hexanamide and heavy thiol probe 4 for 1 hr under dark conditions followed by tryptic digestion for overnight and measured by discovery ABPP based nano LC-MS/MS analysis	ic50	8.4400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, affects expression	2
Thapsigargin	increases reaction, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
tetrahydropalmatine	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1252135	Binding	Induction of quinone reductase activity in human MCF7 cells	Identification of chalcones as in vivo liver monofunctional phase II enzymes inducers. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1M4	Abcam K-562 CRYZ KO	Cancer cell line	Female
CVCL_D2IP	Abcam Raji CRYZ KO	Cancer cell line	Male
CVCL_UQ36	Abcam Jurkat CRYZ KO	Cancer cell line	Male

Clinical trials (associated diseases)

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