CYREN

Summary

CYREN (cell cycle regulator of NHEJ, HGNC:22432) is a protein-coding gene on chromosome 7q33, encoding Cell cycle regulator of non-homologous end joining (Q9BWK5). Cell-cycle-specific regulator of classical non-homologous end joining (NHEJ) of DNA double-strand break (DSB) repair, which can act both as an activator or inhibitor of NHEJ, depending on the cell cycle phase.

Predicted to enable molecular adaptor activity. Involved in double-strand break repair via nonhomologous end joining and negative regulation of double-strand break repair via nonhomologous end joining. Located in cytoplasm and nucleus.

Source: NCBI Gene 78996 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_024033

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22432
Approved symbol	CYREN
Name	cell cycle regulator of NHEJ
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	MGC5242, FLJ27285, CYREN-1, CYREN-2, FLJ22450, MRI, MRI-2
Ensembl gene	ENSG00000122783
Ensembl biotype	protein_coding
OMIM	616980
Entrez	78996

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000393114, ENST00000424142, ENST00000430372, ENST00000459937, ENST00000464070, ENST00000472428, ENST00000477820, ENST00000481410, ENST00000483029, ENST00000486115, ENST00000487774, ENST00000488161, ENST00000617987, ENST00000620897, ENST00000873605, ENST00000873606, ENST00000873607, ENST00000873608, ENST00000873609, ENST00000873610, ENST00000873611, ENST00000938660, ENST00000938661

RefSeq mRNA: 11 — MANE Select: NM_024033 NM_001243749, NM_001243751, NM_001243752, NM_001243753, NM_001243754, NM_001243755, NM_001305629, NM_001305630, NM_001363329, NM_001363330, NM_024033

CCDS: CCDS5838, CCDS59082, CCDS75663

Canonical transcript exons

ENST00000393114 — 4 exons

Exon	Start	End
ENSE00001514200	135165785	135166871
ENSE00001514207	135168786	135169060
ENSE00003496231	135167732	135167807
ENSE00003906715	135170652	135170707

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1248 / max 130.1297, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86348	14.8623	1799
86349	2.0260	1253
86346	1.6635	1024
86347	0.8115	554
86342	0.4994	214
86350	0.2621	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.16	gold quality
right lung	UBERON:0002167	97.78	gold quality
muscle of leg	UBERON:0001383	97.48	gold quality
monocyte	CL:0000576	97.43	gold quality
mononuclear cell	CL:0000842	97.29	gold quality
granulocyte	CL:0000094	97.15	gold quality
leukocyte	CL:0000738	97.15	gold quality
metanephros cortex	UBERON:0010533	96.85	gold quality
right lobe of liver	UBERON:0001114	96.28	gold quality
upper lobe of left lung	UBERON:0008952	96.23	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.12	gold quality
mucosa of stomach	UBERON:0001199	95.63	gold quality
descending thoracic aorta	UBERON:0002345	95.42	gold quality
omental fat pad	UBERON:0010414	95.38	gold quality
upper lobe of lung	UBERON:0008948	95.36	gold quality
peritoneum	UBERON:0002358	95.35	gold quality
tibial nerve	UBERON:0001323	95.25	gold quality
spleen	UBERON:0002106	94.83	gold quality
gall bladder	UBERON:0002110	94.79	gold quality
islet of Langerhans	UBERON:0000006	94.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.61	gold quality
left adrenal gland	UBERON:0001234	94.58	gold quality
body of uterus	UBERON:0009853	94.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.39	gold quality
apex of heart	UBERON:0002098	94.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.28	gold quality
thoracic aorta	UBERON:0001515	94.20	gold quality
rectum	UBERON:0001052	94.17	gold quality
ascending aorta	UBERON:0001496	94.17	gold quality
left coronary artery	UBERON:0001626	94.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting CYREN, 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-9-5P	100.00	72.28	2361
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-581	98.39	67.42	835
HSA-MIR-649	97.96	67.21	704
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-6831-3P	97.49	69.29	505
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-514A-5P	96.94	65.49	801

Literature-anchored findings (GeneRIF, showing 3)

• Characterizes the hamster ortholog and suggests that it may modulate the ability of the proteasome to degrade retroviral cores upon cellular infection. (PMID:17043244)
• Interacts with Ku and enhances efficiency of DNA double strand break ligation in vitro (PMID:24610814)
• proposition that CYREN is a direct cell-cycle-dependent inhibitor of cNHEJ that promotes error-free repair by homologous recombination during cell cycle phases when sister chromatids are present (PMID:28959974)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyren	ENSMUSG00000046806
rattus_norvegicus	Cyren	ENSRNOG00000026958

Protein

Protein identifiers

Cell cycle regulator of non-homologous end joining — Q9BWK5 (reviewed: Q9BWK5)

Alternative names: Modulator of retrovirus infection homolog

All UniProt accessions (2): C9JKC7, Q9BWK5

UniProt curated annotations — full annotation on UniProt →

Function. Cell-cycle-specific regulator of classical non-homologous end joining (NHEJ) of DNA double-strand break (DSB) repair, which can act both as an activator or inhibitor of NHEJ, depending on the cell cycle phase. Acts as a regulator of DNA repair pathway choice by specifically inhibiting classical NHEJ during the S and G2 phases, thereby promoting error-free repair by homologous recombination during cell cycle phases when sister chromatids are present. Preferentially protects single-stranded overhangs at break sites by inhibiting classical NHEJ, thereby creating a local environment that favors homologous recombination. Acts via interaction with XRCC5/Ku80 and XRCC6/Ku70. In contrast, acts as an activator of NHEJ during G1 phase of the cell cycle: promotes classical NHEJ in G1 phase cells via multivalent interactions that increase the affinity of DNA damage response proteins for DSB-associated chromatin. Also involved in immunoglobulin V(D)J recombination. May also act as an indirect regulator of proteasome.

Subunit / interactions. Interacts (via KBM motif) with XRCC5/Ku80 and XRCC6/Ku70 heterodimer. Interacts (via XLF motif) with TRIM28/KAP1, ATM, MRE11, NBN and RAD50. Interacts with splicing factor SF3B1. Interacts with ERCC6L2; this interaction is DNA independent. Does not interact with XRCC5/Ku80 and XRCC6/Ku70 heterodimer. Interacts (via KBM motif) with XRCC5/Ku80 and XRCC6/Ku70 heterodimer.

Subcellular location. Cytoplasm. Nucleus. Chromosome Cytoplasm Cytoplasm.

Domain organisation. The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites. The XLM (XLF-like motif) mediates interaction with DNA damage response proteins TRIM28/KAP1, ATM and members of the MRN complex (MRE11, NBN and RAD50).

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BWK5-1	1, CYREN-1, MRI-1	yes
Q9BWK5-2	2
Q9BWK5-3	3, CYREN-3, MRI-3
Q9BWK5-4	4, CYREN-2, MRI-2

RefSeq proteins (10): NP_001230678, NP_001230680, NP_001230681, NP_001230682, NP_001230683, NP_001230684, NP_001292558, NP_001350258, NP_001350259, NP_076938* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028278	MRI	Family

Pfam: PF15325

UniProt features (18 total): mutagenesis site 5, splice variant 4, short sequence motif 2, compositionally biased region 2, chain 1, region of interest 1, sequence variant 1, helix 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6TYU	X-RAY DIFFRACTION	1.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWK5-F1	66.81	0.19

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 (1): 1

Mutagenesis-validated functional residues (5):

Position	Phenotype
11	abolishes interaction with xrcc5/ku80 and xrcc6/ku70 and ability to inhibit classical non-homologous end joining (nhej).
14	abolishes interaction with xrcc5/ku80 and xrcc6/ku70 and ability to inhibit classical non-homologous end joining (nhej).
16	abolishes interaction with xrcc5/ku80 and xrcc6/ku70 and ability to inhibit classical non-homologous end joining (nhej).
71	does not affect interaction with sf3b1.
153	abolishes interaction with sf3b1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_DNA_REPAIR, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_IMMUNOGLOBULIN_PRODUCTION, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SOMATIC_DIVERSIFICATION_OF_IMMUNE_RECEPTORS, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION

GO Biological Process (7): double-strand break repair via nonhomologous end joining (GO:0006303), immunoglobulin V(D)J recombination (GO:0033152), protein localization to site of double-strand break (GO:1990166), negative regulation of double-strand break repair via nonhomologous end joining (GO:2001033), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (2): damaged DNA binding (GO:0003684), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), site of double-strand break (GO:0035861), DNA repair complex (GO:1990391), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
double-strand break repair via nonhomologous end joining	2
regulation of double-strand break repair via nonhomologous end joining	2
double-strand break repair	1
somatic recombination of immunoglobulin gene segments	1
V(D)J recombination	1
protein localization to chromosome	1
negative regulation of double-strand break repair	1
positive regulation of double-strand break repair	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
site of DNA damage	1
catalytic complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYREN	XRCC6	P12956	905
CYREN	MRI1	Q9BV20	890
CYREN	XRCC5	P13010	878
CYREN	AMHR2	Q16671	783
CYREN	CTNND2	Q9UQB3	760
CYREN	PAXX	Q9BUH6	686
CYREN	XRCC4	Q13426	685
CYREN	ROPN1L	Q96C74	637
CYREN	PRKDC	P78527	624
CYREN	NHEJ1	Q9H9Q4	607
CYREN	ERCC6L2	Q5T890	560
CYREN	APLF	Q8IW19	533
CYREN	ATM	Q13315	515
CYREN	TERT	O14746	497
CYREN	NBDY	A0A0U1RRE5	447

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ERCC6L2	CYREN	psi-mi:“MI:0915”(physical association)	0.560
CYREN	MKLN1	psi-mi:“MI:0915”(physical association)	0.560
CYREN	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
CYREN	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ECE1	CYREN	psi-mi:“MI:0915”(physical association)	0.370
CYREN	ACOX1	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
MKLN1	CYREN	psi-mi:“MI:0915”(physical association)	0.000
CYREN	ERCC6L2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): ERCC6L2 (Two-hybrid), C7orf49 (Reconstituted Complex), C7orf49 (Reconstituted Complex), MKLN1 (Two-hybrid), ERCC6L2 (Two-hybrid), RBMXL1 (Affinity Capture-MS), UTP11L (Affinity Capture-MS), PRRC2B (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), BDH2 (Affinity Capture-MS), FOCAD (Affinity Capture-MS), DHRS11 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), LPCAT4 (Affinity Capture-MS), PRKDC (Affinity Capture-Western)

ESM2 similar proteins: A2AI08, A6QLA6, A9JRX0, B2RYR0, D3ZUI5, E1BXS0, O35144, O75128, P0DPK0, Q09HN1, Q0IIM1, Q13111, Q15554, Q2TAK8, Q3U1C4, Q3U2K0, Q58CQ0, Q5M9G5, Q5NBX1, Q5PQK4, Q5U5Q9, Q5XHX2, Q68DK7, Q6A000, Q6AYH4, Q6P1D7, Q6P1H6, Q6PB51, Q6PDM1, Q6Y685, Q7TP65, Q7Z2Z1, Q80Y19, Q8BHZ5, Q8BRV5, Q8C5R2, Q8IWD4, Q8IY92, Q8IYW5, Q8K4R9

Diamond homologs: Q09HN1, Q6AYH4, Q8BHZ5, Q9BWK5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1907 predictions. Top by Δscore:

Variant	Effect	Δscore
7:135167806:GT:G	acceptor_gain	1.0000
7:135167808:C:CC	acceptor_gain	1.0000
7:135170507:T:TA	donor_gain	1.0000
7:135134839:A:AG	acceptor_gain	0.9900
7:135134840:G:GG	acceptor_gain	0.9900
7:135134840:GACT:G	acceptor_gain	0.9900
7:135134840:GACTA:G	acceptor_gain	0.9900
7:135148194:G:GT	donor_gain	0.9900
7:135148271:G:GG	donor_gain	0.9900
7:135164413:CGCA:C	acceptor_loss	0.9900
7:135164414:GCAG:G	acceptor_loss	0.9900
7:135164415:CA:C	acceptor_loss	0.9900
7:135164417:G:GA	acceptor_loss	0.9900
7:135167726:CTTTA:C	donor_loss	0.9900
7:135167727:TTTA:T	donor_loss	0.9900
7:135167728:TTA:T	donor_loss	0.9900
7:135167729:TA:T	donor_loss	0.9900
7:135167730:A:C	donor_loss	0.9900
7:135167731:C:CT	donor_loss	0.9900
7:135167803:GGAGT:G	acceptor_gain	0.9900
7:135167805:AGTC:A	acceptor_loss	0.9900
7:135167806:GTCT:G	acceptor_loss	0.9900
7:135167807:TCT:T	acceptor_loss	0.9900
7:135167808:CT:C	acceptor_loss	0.9900
7:135167809:T:C	acceptor_loss	0.9900
7:135168671:TGAAA:T	donor_gain	0.9900
7:135168876:C:CT	acceptor_gain	0.9900
7:135170106:A:AC	donor_gain	0.9900
7:135170234:T:TA	donor_gain	0.9900
7:135170297:C:CA	donor_gain	0.9900

AlphaMissense

1026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:135166617:G:C	F156L	0.993
7:135166617:G:T	F156L	0.993
7:135166619:A:G	F156L	0.993
7:135167751:G:T	A65D	0.993
7:135166624:A:G	I154T	0.992
7:135166620:A:C	F155L	0.991
7:135166620:A:T	F155L	0.991
7:135166622:A:G	F155L	0.991
7:135166624:A:C	I154S	0.990
7:135166633:A:T	V151D	0.990
7:135168877:A:G	W16R	0.990
7:135168877:A:T	W16R	0.990
7:135166621:A:G	F155S	0.984
7:135167760:A:T	V62D	0.984
7:135166627:T:A	E153V	0.982
7:135168875:C:A	W16C	0.981
7:135168875:C:G	W16C	0.981
7:135167752:C:G	A65P	0.980
7:135166630:C:G	R152P	0.979
7:135167766:T:A	E60V	0.979
7:135167771:C:A	E58D	0.979
7:135167771:C:G	E58D	0.979
7:135167739:A:G	L69P	0.978
7:135167777:C:A	M56I	0.977
7:135167777:C:G	M56I	0.977
7:135167777:C:T	M56I	0.977
7:135168890:C:A	R11S	0.977
7:135168890:C:G	R11S	0.977
7:135166618:A:G	F156S	0.975
7:135166624:A:T	I154N	0.975

dbSNP variants (sampled 300 via entrez): RS1000003403 (7:135162789 T>C), RS1000021723 (7:135131448 GA>G), RS1000057053 (7:135156203 T>G), RS1000160436 (7:135104120 C>A,G), RS1000206857 (7:135104834 C>T), RS1000219302 (7:135156848 G>A), RS1000253092 (7:135153379 GGGAGGC>G), RS1000260499 (7:135104508 G>A), RS1000271498 (7:135138693 T>C,G), RS1000318934 (7:135112744 T>A,G), RS1000368839 (7:135098236 T>C), RS1000374642 (7:135142710 C>A), RS1000376785 (7:135145633 GCAAA>G), RS1000471687 (7:135146082 A>G), RS1000496293 (7:135171465 A>G,T)

Disease associations

OMIM: gene MIM:616980 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	2
Lead	affects expression, affects methylation	2
Tobacco Smoke Pollution	increases expression, decreases methylation	2
Valproic Acid	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
entinostat	decreases expression	1
K 7174	decreases expression	1
torcetrapib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Panobinostat	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Coumestrol	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Etoposide	affects localization	1
Methyl Methanesulfonate	increases expression	1
Phenylmercuric Acetate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SG35	HAP1 C7orf49 (-) 1	Cancer cell line	Male
CVCL_SG36	HAP1 C7orf49 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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