CRYZ

protein-coding

crystallin zeta

Gene summary

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. [provided by RefSeq, Sep 2008]

MANE transcript

NM_001889.4

Inheritance

—

ClinVar variants

U:48B:8

Top phenotype

CRYZ-related disorder

gnomAD constraint

pLI —, LoF o/e 1.57

Max pathogenic AF

—

Genomic locus

chr1:74,705,482-74,733,408

External References & Databases

Ensembl (ENSG00000116791)

Transcript & Mutation Effects

hg38 • Region Span ~27.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRYZ variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 38

CRYZ-related disorderTotal: 11

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001889.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	2 clinvar	2 clinvar	6
missense			45 clinvar	1 clinvar	1 clinvar	47
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)				2 clinvar		2
Total	0	0	48	5	3	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 113 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001889.4	RefSeq	NP_001880.2	8	MANE Select
ENST00000340866.10	Ensembl	ENSP00000339399.5	8	MANE Select
NM_001130042.2	RefSeq	NP_001123514.1	8	Standard
NM_001130043.2	RefSeq	NP_001123515.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

oxidative stress induced gene expression via nrf2

Biological Process

visual perception
xenobiotic catabolic process
protein homotetramerization
oxidation-reduction process

Molecular Function

mRNA 3'-UTR binding
NADPH:quinone reductase activity
zinc ion binding
NADPH binding
NADH binding

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000417775
Coding exons: 8
Length: 27923
Individuals with no LoFs: 125265
Homozygous LoFs: 3
Heterozygous LoFs: 478
Defined: 125746
p: 0.00191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.381	162	176	0.919	0.00000842	2111
Missense (PolyPhen)		43	51.258	0.83889		575
Synonymous	-0.0219	62	61.8	1.00	0.00000309	658
Loss of Function	-2.22	28	17.9	1.57	0.00000110	207

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0061	0.0058	notable
Latino/Admixed American	0.00041	0.00038	rare
Ashkenazi Jewish	0.0030	0.0030	notable
East Asian	0.0045	0.0044	notable
Finnish	0.00042	0.00037	rare
European (Non-Finnish)	0.0015	0.0014	notable
South Asian	0.0029	0.0028	notable
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Does not have alcohol dehydrogenase activity. Binds NADP and acts through a one-electron transfer process. Orthoquinones, such as 1,2-naphthoquinone or 9,10-phenanthrenequinone, are the best substrates (in vitro). May act in the detoxification of xenobiotics. Interacts with (AU)-rich elements (ARE) in the 3'-UTR of target mRNA species. Enhances the stability of mRNA coding for BCL2. NADPH binding interferes with mRNA binding. {ECO:0000269|PubMed:17497241, ECO:0000269|PubMed:20103721}.;

Recessive Scores

pRec: 0.421

Intolerance Scores

LoFtool: 0.997
RVIS EVS: 0.46
RVIS percentile EVS: 78.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.514

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium