CRYZL1

Summary

CRYZL1 (crystallin zeta like 1, HGNC:2420) is a protein-coding gene on chromosome 21q22.11, encoding Ferry endosomal RAB5 effector complex subunit 4 (O95825). Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary).

This gene encodes a protein that has sequence similarity to zeta crystallin, also known as quinone oxidoreductase. This zeta crystallin-like protein also contains an NAD(P)H binding site. Alternatively spliced transcript variants have been observed but their full-length nature has not been completely determined.

Source: NCBI Gene 9946 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 64 total — 3 pathogenic
• MANE Select transcript: NM_145858

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2420
Approved symbol	CRYZL1
Name	crystallin zeta like 1
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	QOH-1, 4P11, Fy-4, FERRY4
Ensembl gene	ENSG00000205758
Ensembl biotype	protein_coding
OMIM	603920
Entrez	9946

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 24 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000290244, ENST00000361534, ENST00000381540, ENST00000381554, ENST00000399442, ENST00000413017, ENST00000414079, ENST00000417979, ENST00000420072, ENST00000426935, ENST00000429827, ENST00000431177, ENST00000437996, ENST00000438788, ENST00000440526, ENST00000441940, ENST00000445393, ENST00000452420, ENST00000468349, ENST00000479964, ENST00000480893, ENST00000488167, ENST00000490714, ENST00000949546, ENST00000949547, ENST00000949548, ENST00000949549, ENST00000949550, ENST00000949551, ENST00000949552, ENST00000949553, ENST00000949554, ENST00000949555

RefSeq mRNA: 1 — MANE Select: NM_145858 NM_145858

CCDS: CCDS13633

Canonical transcript exons

ENST00000381554 — 13 exons

Exon	Start	End
ENSE00001387385	33602234	33602345
ENSE00001603968	33589341	33589921
ENSE00001722894	33641681	33641741
ENSE00003493157	33599150	33599248
ENSE00003499413	33595731	33595836
ENSE00003502265	33613538	33613606
ENSE00003528796	33624683	33624760
ENSE00003547975	33603404	33603537
ENSE00003596663	33597280	33597401
ENSE00003635139	33616706	33616750
ENSE00003635551	33591162	33591207
ENSE00003642759	33631486	33631557
ENSE00003683733	33621996	33622068

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 96.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.4574 / max 545.4373, expressed in 1786 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190264	17.3904	1785
190265	0.0670	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.30	gold quality
ganglionic eminence	UBERON:0004023	95.85	gold quality
mucosa of stomach	UBERON:0001199	95.64	gold quality
popliteal artery	UBERON:0002250	95.27	gold quality
tibial artery	UBERON:0007610	95.27	gold quality
artery	UBERON:0001637	95.02	gold quality
aorta	UBERON:0000947	94.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.46	gold quality
ventricular zone	UBERON:0003053	94.44	gold quality
descending thoracic aorta	UBERON:0002345	94.41	gold quality
anterior cingulate cortex	UBERON:0009835	94.31	gold quality
left ovary	UBERON:0002119	94.23	gold quality
cingulate cortex	UBERON:0003027	94.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.09	gold quality
lower esophagus	UBERON:0013473	94.06	gold quality
amygdala	UBERON:0001876	94.02	gold quality
right coronary artery	UBERON:0001625	94.01	gold quality
calcaneal tendon	UBERON:0003701	93.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.98	gold quality
body of uterus	UBERON:0009853	93.97	gold quality
tibial nerve	UBERON:0001323	93.91	gold quality
right uterine tube	UBERON:0001302	93.89	gold quality
left coronary artery	UBERON:0001626	93.84	gold quality
substantia nigra pars compacta	UBERON:0001965	93.79	gold quality
right ovary	UBERON:0002118	93.67	gold quality
ascending aorta	UBERON:0001496	93.54	gold quality
thoracic aorta	UBERON:0001515	93.54	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.50	gold quality
coronary artery	UBERON:0001621	93.48	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.23
E-GEOD-99795	no	117.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting CRYZL1, 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-4533	100.00	69.48	2758
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508
HSA-MIR-664B-5P	96.74	67.50	509

Literature-anchored findings (GeneRIF, showing 1)

• Data show that human and yeast zeta-crystallins bind AU-rich elements in RNA. (PMID:17497241)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cryzl1	ENSDARG00000026902
mus_musculus	Cryzl1	ENSMUSG00000058240
rattus_norvegicus	Cryzl1	ENSRNOG00000028014
rattus_norvegicus		ENSRNOG00000073755
caenorhabditis_elegans		WBGENE00010790
caenorhabditis_elegans		WBGENE00010791
caenorhabditis_elegans		WBGENE00017060

Paralogs (17): PTGR1 (ENSG00000106853), VAT1 (ENSG00000108828), TP53I3 (ENSG00000115129), MECR (ENSG00000116353), CRYZ (ENSG00000116791), RTN4IP1 (ENSG00000130347), PTGR2 (ENSG00000140043), SORD (ENSG00000140263), VAT1L (ENSG00000171724), ADH6 (ENSG00000172955), PTGR3 (ENSG00000180011), ADH1A (ENSG00000187758), ADH7 (ENSG00000196344), ADH1B (ENSG00000196616), ADH5 (ENSG00000197894), ADH4 (ENSG00000198099), ADH1C (ENSG00000248144)

Protein

Protein identifiers

Ferry endosomal RAB5 effector complex subunit 4 — O95825 (reviewed: O95825)

Alternative names: Crystallin zeta like 1, Protein 4P11, Quinone oxidoreductase homolog 1

All UniProt accessions (17): A0A0C4DG14, A6NHJ8, A6NMA8, A6NND8, A8MZ10, C9JAL0, C9JNR9, C9JQD0, C9JZK8, C9K0F7, O95825, F8WF64, H7C0X3, H7C2K1, H7C338, H7C3I5, H7C3S0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary). The FERRY complex directly interacts with mRNAs and RAB5A, and functions as a RAB5A effector involved in the localization and the distribution of specific mRNAs most likely by mediating their endosomal transport. The complex recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction.

Subunit / interactions. Homodimer. Component of the FERRY complex composed of five subunits, TBCK, PPP1R21, FERRY3, CRYZL1 and GATD1 with a ratio of 1:2:1:2:4, respectively.

Subcellular location. Early endosome.

Tissue specificity. Ubiquitous.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O95825-1	1	yes
O95825-2	2

RefSeq proteins (1): NP_665857* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011032	GroES-like_sf	Homologous_superfamily
IPR013154	ADH-like_N	Domain
IPR020843	ER	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR042633	CRYZL1	Family

Pfam: PF08240

UniProt features (37 total): strand 16, helix 12, sequence conflict 4, splice variant 2, chain 1, binding site 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8A3O	X-RAY DIFFRACTION	2.9
7ND2	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95825-F1	91.71	0.78

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 (1): 156

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): RRAGTTGT_UNKNOWN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GGCNKCCATNK_UNKNOWN, MODULE_313, CEBP_Q2, MYOD_01, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, OCT1_07, AACTTT_UNKNOWN, TCCAGAT_MIR5165P, GFI1_01, TGAGATT_MIR216, POU3F2_02, RFX1_02

GO Biological Process (1): quinone metabolic process (GO:1901661)

GO Molecular Function (5): oxidoreductase activity (GO:0016491), identical protein binding (GO:0042802), quinone reductase (NADPH) activity (GO:0003960), protein binding (GO:0005515), NADP binding (GO:0050661)

GO Cellular Component (3): early endosome (GO:0005769), cytosol (GO:0005829), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ketone metabolic process	1
catalytic activity	1
protein binding	1
NADPH dehydrogenase activity	1
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	1
binding	1
adenyl nucleotide binding	1
endosome	1
cytoplasm	1
cellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYZL1	LAP3	P28838	861
CRYZL1	MT2A	P02795	762
CRYZL1	SLC40A1	Q9NP59	715
CRYZL1	PSMG1	O95456	567
CRYZL1	URB1	O60287	551
CRYZL1	CFAP298	P57076	544
CRYZL1	CRYL1	Q9Y2S2	532
CRYZL1	CRYM	Q14894	530
CRYZL1	LGSN	Q5TDP6	519
CRYZL1	CRYBG3	Q68DQ2	488
CRYZL1	TMEM50B	P56557	485
CRYZL1	BRWD1	Q9NSI6	468
CRYZL1	DONSON	Q9NYP3	464
CRYZL1	CRYGN	Q8WXF5	447
CRYZL1	TMEM242	Q9NWH2	414

IntAct

38 interactions, top by confidence:

A	B	Type	Score
FERRY3	CRYZL1	psi-mi:“MI:0915”(physical association)	0.690
ITPK1	CRYZL1	psi-mi:“MI:0915”(physical association)	0.590
PPP1R21	CRYZL1	psi-mi:“MI:0407”(direct interaction)	0.590
GATD1	CRYZL1	psi-mi:“MI:0915”(physical association)	0.570
PLXNA4	CRYZL1	psi-mi:“MI:0915”(physical association)	0.560
PLXNA4	CRYZL1	psi-mi:“MI:0914”(association)	0.560
CFAP52	ASMTL	psi-mi:“MI:0914”(association)	0.530
FBXL14	CRYZL1	psi-mi:“MI:0914”(association)	0.530
TCP10L	CRYZL1	psi-mi:“MI:0914”(association)	0.530
CRYZL1	CRYZL1	psi-mi:“MI:0407”(direct interaction)	0.440
PLXNA4	CRYZL1	psi-mi:“MI:0915”(physical association)	0.400
GATD1		psi-mi:“MI:0915”(physical association)	0.400
CRYZL1	GAMT	psi-mi:“MI:0915”(physical association)	0.400
HSCB	CRYZL1	psi-mi:“MI:0915”(physical association)	0.370
Ctnnbl1	LCMT2	psi-mi:“MI:0914”(association)	0.350
Tbck	FAM20B	psi-mi:“MI:0914”(association)	0.350
PPP1R21		psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
TAFA3	FUOM	psi-mi:“MI:0914”(association)	0.350
TCP10L	RNF40	psi-mi:“MI:0914”(association)	0.350
IL6R	MID1	psi-mi:“MI:0914”(association)	0.350
RAB5A	CRYZL1	psi-mi:“MI:0914”(association)	0.350
ANKRD39	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (42): CRYZL1 (Affinity Capture-RNA), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS)

ESM2 similar proteins: A4FUF0, A6NNS2, A9UM79, D3ZGP9, G3X9X1, O54929, O94955, O95825, P10868, P14893, P26149, P27365, P42694, Q0P5D8, Q0V8J1, Q1RMJ5, Q3UFS0, Q49A26, Q4R7G8, Q53H12, Q562D5, Q59A28, Q5IFP1, Q5R7T2, Q5RAF1, Q5RED7, Q5RJL2, Q5RKH0, Q5RKN4, Q5ZLS7, Q62878, Q6DFV5, Q6PC62, Q86XA0, Q8CA95, Q8CHS7, Q8IX04, Q8N475, Q8VCM5, Q8VHQ9

Diamond homologs: A0A075TRC0, A0A0B5KU17, A0A0C1E3C9, A0A0D2YG10, A0A0S6XH49, A0A1L7U3D7, A0A1L9WN37, A0A1R3RGK0, A0A1W5T1T1, A0A284RE13, A0A2H3CTK0, A0A2I2F262, A0A2V5GX43, A0A345BJP0, A0A348HAX6, A0A3G1DJH7, A0A3G9GQ29, A0A411KUP8, A0A481WNP4, A0A4P8DJV2, A0A6F9DXA0, A1CFL8, A2R6H1, B3FWT3, B4ER97, B4XYB8, B6HNK3, B8MKY6, B8MV59, B8NYX0, C5FM57, C5H885, D4AU31, E0D202, E5A7D9, E9F5E7, E9F8M3, G0R6S8, G0REX6, G3J9P0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1072704	NC_000021.8:g.(?34540717)(35013574_?)del	Pathogenic
3062422	GRCh37/hg19 21q22.11(chr21:34809971-34966753)x1	Pathogenic
59012	GRCh38/hg38 21q22.11(chr21:33465408-33806416)x1	Pathogenic

SpliceAI

2893 predictions. Top by Δscore:

Variant	Effect	Δscore
21:33589732:T:TA	donor_gain	1.0000
21:33597403:T:C	acceptor_gain	1.0000
21:33597419:T:C	acceptor_gain	1.0000
21:33597419:T:TC	acceptor_gain	1.0000
21:33599245:CGGG:C	acceptor_gain	1.0000
21:33599249:C:CC	acceptor_gain	1.0000
21:33603403:CA:C	donor_gain	1.0000
21:33613536:AC:A	donor_gain	1.0000
21:33613537:CC:C	donor_gain	1.0000
21:33613604:TTCC:T	acceptor_loss	1.0000
21:33613605:TCCT:T	acceptor_loss	1.0000
21:33613606:CCTA:C	acceptor_loss	1.0000
21:33613607:C:CC	acceptor_gain	1.0000
21:33613607:CT:C	acceptor_loss	1.0000
21:33613607:CTAAA:C	acceptor_loss	1.0000
21:33613608:T:A	acceptor_loss	1.0000
21:33616751:C:CC	acceptor_gain	1.0000
21:33621993:TACCA:T	donor_loss	1.0000
21:33621995:C:A	donor_loss	1.0000
21:33624677:CAATA:C	donor_loss	1.0000
21:33624678:AATAC:A	donor_loss	1.0000
21:33624679:ATAC:A	donor_loss	1.0000
21:33624680:TACCT:T	donor_loss	1.0000
21:33624681:A:C	donor_loss	1.0000
21:33624682:C:CA	donor_loss	1.0000
21:33624694:T:C	donor_gain	1.0000
21:33624757:CTTC:C	acceptor_gain	1.0000
21:33624758:TTCC:T	acceptor_loss	1.0000
21:33624759:TCCT:T	acceptor_loss	1.0000
21:33624759:TCCTA:T	acceptor_loss	1.0000

AlphaMissense

2281 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:33597306:A:G	W258R	0.995
21:33597306:A:T	W258R	0.995
21:33599164:A:T	V221D	0.990
21:33603423:A:G	L149P	0.989
21:33622004:A:T	V70E	0.988
21:33595767:A:G	W290R	0.986
21:33595767:A:T	W290R	0.986
21:33622010:C:T	G68E	0.986
21:33602318:C:G	A165P	0.984
21:33624712:C:G	A39P	0.984
21:33616706:C:G	G88R	0.983
21:33616706:C:T	G88R	0.983
21:33603530:T:A	K113N	0.982
21:33603530:T:G	K113N	0.982
21:33613606:C:T	G88E	0.982
21:33602317:G:T	A165E	0.981
21:33622014:C:G	A67P	0.980
21:33597305:C:G	W258S	0.978
21:33603465:G:T	A135D	0.977
21:33603466:C:G	A135P	0.977
21:33603483:C:T	G129E	0.977
21:33603505:C:G	A122P	0.977
21:33622028:A:T	V62D	0.977
21:33589832:A:T	V347D	0.976
21:33595783:G:C	F284L	0.975
21:33595783:G:T	F284L	0.975
21:33595785:A:G	F284L	0.975
21:33597343:T:A	K245N	0.975
21:33597343:T:G	K245N	0.975
21:33603426:A:T	V148E	0.975

dbSNP variants (sampled 300 via entrez): RS1000043894 (21:33624271 G>T), RS1000082170 (21:33596659 A>AATAAAAAT), RS1000109091 (21:33616758 G>T), RS1000130429 (21:33594638 C>T), RS1000147093 (21:33633320 A>T), RS1000263440 (21:33624359 C>T), RS1000306470 (21:33636933 A>G), RS1000308063 (21:33634500 T>C), RS1000358501 (21:33637296 T>C), RS1000455951 (21:33630928 T>C), RS1000524218 (21:33597857 G>A,C), RS1000541132 (21:33604049 G>A,C), RS1000543096 (21:33642560 G>A), RS1000624636 (21:33628182 C>T), RS1000625172 (21:33591711 G>A)

Disease associations

OMIM: gene MIM:603920 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002598_2	Educational attainment	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression, increases expression	1
sodium arsenate	increases expression	1
quercitrin	decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, 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
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Catechin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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