ZYG11A

Summary

ZYG11A (zyg-11 family member A, cell cycle regulator, HGNC:32058) is a protein-coding gene on chromosome 1p32.3, encoding Protein zyg-11 homolog A (Q6WRX3). Probably acts as a target recruitment subunit in an E3 ubiquitin ligase complex ZYGA-CUL2-elongin BC.

Predicted to be part of Cul2-RING ubiquitin ligase complex.

Source: NCBI Gene 440590 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 128 total
• MANE Select transcript: NM_001004339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32058
Approved symbol	ZYG11A
Name	zyg-11 family member A, cell cycle regulator
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	ZYG11
Ensembl gene	ENSG00000203995
Ensembl biotype	protein_coding
OMIM	618675
Entrez	440590

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000371528, ENST00000371532

RefSeq mRNA: 2 — MANE Select: NM_001004339 NM_001004339, NM_001307931

CCDS: CCDS44148, CCDS76166

Canonical transcript exons

ENST00000371528 — 14 exons

Exon	Start	End
ENSE00001455440	52856998	52857749
ENSE00001455443	52842760	52842973
ENSE00001455449	52892782	52894998
ENSE00001455450	52886956	52887053
ENSE00001455452	52885833	52885894
ENSE00001455453	52881471	52881665
ENSE00001455454	52877925	52877969
ENSE00001455455	52877682	52877843
ENSE00001455456	52867727	52867777
ENSE00001455457	52867539	52867638
ENSE00001455458	52866503	52866567
ENSE00001455459	52863981	52864157
ENSE00003512107	52854465	52854630
ENSE00003568365	52860731	52860871

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 92.79.

FANTOM5 (CAGE): breadth broad, TPM avg 3.9589 / max 209.5075, expressed in 634 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2891	1.5715	398
2894	1.2145	452
2895	0.5378	304
2889	0.3387	129
2890	0.1769	62
2893	0.0662	19
2892	0.0532	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	92.79	gold quality
secondary oocyte	CL:0000655	92.24	gold quality
buccal mucosa cell	CL:0002336	85.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.15	gold quality
kidney epithelium	UBERON:0004819	79.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.30	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.23	gold quality
left ventricle myocardium	UBERON:0006566	68.96	gold quality
esophagus squamous epithelium	UBERON:0006920	63.66	silver quality
right lobe of thyroid gland	UBERON:0001119	63.42	gold quality
endothelial cell	CL:0000115	63.27	gold quality
thyroid gland	UBERON:0002046	62.68	gold quality
left lobe of thyroid gland	UBERON:0001120	62.61	gold quality
testis	UBERON:0000473	62.29	gold quality
bone marrow cell	CL:0002092	60.62	gold quality
right testis	UBERON:0004534	60.50	gold quality
right lobe of liver	UBERON:0001114	60.39	gold quality
adult mammalian kidney	UBERON:0000082	59.44	gold quality
liver	UBERON:0002107	59.21	gold quality
left testis	UBERON:0004533	59.17	gold quality
amniotic fluid	UBERON:0000173	59.10	gold quality
myocardium	UBERON:0002349	58.16	gold quality
lower esophagus mucosa	UBERON:0035834	57.85	gold quality
kidney	UBERON:0002113	57.42	gold quality
gingival epithelium	UBERON:0001949	57.15	gold quality
pancreatic ductal cell	CL:0002079	56.09	silver quality
adult organism	UBERON:0007023	55.38	silver quality
gingiva	UBERON:0001828	54.78	gold quality
esophagus mucosa	UBERON:0002469	54.26	gold quality
tonsil	UBERON:0002372	54.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	15.52
E-ANND-3	yes	4.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ZYG11A, 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-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-5584-5P	99.49	68.22	2814

Literature-anchored findings (GeneRIF, showing 4)

• Over-expression of ZYG11A is associated with non-small cell lung cancer. (PMID:26771237)
• the ubiquitin ligase CRL2(ZYG-11) redundantly targets the degradation of cyclin B1 in Caenorhabditis elegans and human cells. (PMID:27810909)
• Autosomal dominant diabetes associated with a novel ZYG11A mutation resulting in cell cycle arrest in beta-cells. (PMID:33321115)
• ZYG11A Is Expressed in Epithelial Ovarian Cancer and Correlates With Low Grade Disease. (PMID:34220714)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zyg11	ENSDARG00000007737
danio_rerio	zyg11l	ENSDARG00000101799
mus_musculus	Zyg11a	ENSMUSG00000034645
rattus_norvegicus	Zyg11a	ENSRNOG00000010885
caenorhabditis_elegans		WBGENE00006996

Paralogs (2): ZER1 (ENSG00000160445), ZYG11B (ENSG00000162378)

Protein

Protein identifiers

Protein zyg-11 homolog A — Q6WRX3 (reviewed: Q6WRX3)

All UniProt accessions (1): Q6WRX3

UniProt curated annotations — full annotation on UniProt →

Function. Probably acts as a target recruitment subunit in an E3 ubiquitin ligase complex ZYGA-CUL2-elongin BC.

Similarity. Belongs to the zyg-11 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6WRX3-1	1	yes
Q6WRX3-2	2

RefSeq proteins (2): NP_001004339, NP_001294860 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR051341	Zyg-11_UBL_adapter	Family
IPR055142	ZER1-like_C	Domain

Pfam: PF22964

UniProt features (5 total): repeat 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6WRX3-F1	90.55	0.80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 46 (showing top): GOCC_TRANSFERASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, GOCC_CUL2_RING_UBIQUITIN_LIGASE_COMPLEX, GSE13522_CTRL_VS_T_CRUZI_G_STRAIN_INF_SKIN_DN, E2F5_TARGET_GENES, HSD17B8_TARGET_GENES, UBN1_TARGET_GENES, ZNF282_TARGET_GENES, ZNF664_TARGET_GENES, ZNF8_TARGET_GENES, MIR579_3P, MIR664B_3P, MIR577, MIR548M

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): Cul2-RING ubiquitin ligase complex (GO:0031462)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZYG11A	CUL2	Q13617	786
ZYG11A	LRR1	Q96L50	703
ZYG11A	ZNF142	P52746	472
ZYG11A	HAL	P42357	467
ZYG11A	ELOC	Q15369	464
ZYG11A	PAEP	P09466	436
ZYG11A	UNC119	Q13432	405
ZYG11A	TEX13B	Q9BXU2	397
ZYG11A	RBX1	P62877	375
ZYG11A	TBC1D21	Q8IYX1	374
ZYG11A	NKIRAS2	Q9NYR9	370
ZYG11A	MEX3D	Q86XN8	366
ZYG11A	LRRC3	Q9BY71	365
ZYG11A	VHL	P40337	361
ZYG11A	MSANTD3	Q96H12	353

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ZNF169	ZNF316	psi-mi:“MI:0914”(association)	0.530
BMERB1	DCTN6	psi-mi:“MI:0914”(association)	0.530
ZNF483	ZNF197	psi-mi:“MI:0914”(association)	0.530
HOXB2	ZYG11A	psi-mi:“MI:0915”(physical association)	0.400
FEZ1		psi-mi:“MI:0914”(association)	0.350
ZNF264	TRIM24	psi-mi:“MI:0914”(association)	0.350
ZNF695	TRIM24	psi-mi:“MI:0914”(association)	0.350
ZNF547	ARPC4-TTLL3	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
ZNF460	ZNF320	psi-mi:“MI:0914”(association)	0.350
KRT38	KRBA1	psi-mi:“MI:0914”(association)	0.350
ZNF738	KRBA1	psi-mi:“MI:0914”(association)	0.350
FEZ1	POLRMT	psi-mi:“MI:0914”(association)	0.350
ZNF695	RTCA	psi-mi:“MI:0914”(association)	0.350
ZNF484	ZNF195	psi-mi:“MI:0914”(association)	0.350
ZNF418	ZNF195	psi-mi:“MI:0914”(association)	0.350
ZNF776	TRIM24	psi-mi:“MI:0914”(association)	0.350
ATF6	IGHG2	psi-mi:“MI:0914”(association)	0.350
SIKE1	ALDH7A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Proximity Label-MS), ZYG11A (Affinity Capture-RNA), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), ZYG11A (Affinity Capture-MS)

ESM2 similar proteins: A0JM56, A0JPI9, A2BFL2, A5PK13, A6H639, J9SQF3, O13066, P19686, P33402, Q02108, Q0VAA2, Q14BP6, Q15111, Q15813, Q3USB7, Q498T9, Q4R642, Q4V8D9, Q4ZHS0, Q5DU41, Q5FVQ9, Q5RAG3, Q5RBD9, Q5RJH2, Q5ZIJ9, Q5ZIU8, Q62688, Q68F79, Q6DN12, Q6GQN5, Q6NU09, Q6P9F7, Q6WRX3, Q7Z7L7, Q80ZJ6, Q8BG40, Q8CDU4, Q8CIR4, Q8CIV8, Q8HXA6

Diamond homologs: A0JMZ3, A2BFL2, P21541, Q3UFS0, Q5RAG3, Q5TYQ1, Q6WRX3, Q7Z7L7, Q80ZJ6, Q9C0D3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	110
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2829 predictions. Top by Δscore:

Variant	Effect	Δscore
1:52854591:G:GT	donor_gain	1.0000
1:52854591:G:T	donor_gain	1.0000
1:52860725:TTTCA:T	acceptor_loss	1.0000
1:52860726:TTCAG:T	acceptor_loss	1.0000
1:52860727:TCAGG:T	acceptor_loss	1.0000
1:52860728:CA:C	acceptor_loss	1.0000
1:52860845:G:GT	donor_gain	1.0000
1:52866501:A:G	acceptor_gain	1.0000
1:52867725:A:AG	acceptor_gain	1.0000
1:52867726:G:GG	acceptor_gain	1.0000
1:52877848:G:T	donor_gain	1.0000
1:52877856:GAT:G	donor_gain	1.0000
1:52881442:T:TA	acceptor_gain	1.0000
1:52881443:G:A	acceptor_gain	1.0000
1:52887026:GC:G	donor_gain	1.0000
1:52887054:G:GG	donor_gain	1.0000
1:52842969:TACAG:T	donor_loss	0.9900
1:52842970:ACAG:A	donor_loss	0.9900
1:52842971:CAGG:C	donor_loss	0.9900
1:52842972:AGGT:A	donor_loss	0.9900
1:52842974:G:GA	donor_loss	0.9900
1:52842975:T:G	donor_loss	0.9900
1:52854459:T:TA	acceptor_gain	0.9900
1:52854460:GCTA:G	acceptor_loss	0.9900
1:52854463:A:AG	acceptor_gain	0.9900
1:52854463:AGGA:A	acceptor_loss	0.9900
1:52854464:G:GG	acceptor_gain	0.9900
1:52854464:GGAA:G	acceptor_gain	0.9900
1:52854577:G:GT	donor_gain	0.9900
1:52854590:GGAA:G	donor_gain	0.9900

AlphaMissense

5018 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:52864038:A:C	S403R	0.986
1:52864040:T:A	S403R	0.986
1:52864040:T:G	S403R	0.986
1:52857430:T:C	L230S	0.979
1:52887014:T:A	W689R	0.977
1:52887014:T:C	W689R	0.977
1:52857684:T:C	F315L	0.974
1:52857686:T:A	F315L	0.974
1:52857686:T:G	F315L	0.974
1:52877767:T:C	L543P	0.973
1:52857370:T:C	L210S	0.972
1:52864036:C:A	A402D	0.972
1:52864057:T:C	L409P	0.966
1:52857439:T:C	L233P	0.963
1:52864044:T:C	C405R	0.960
1:52857379:C:T	S213F	0.959
1:52857610:T:C	L290S	0.959
1:52857694:T:C	L318P	0.958
1:52877760:T:A	W541R	0.958
1:52877760:T:C	W541R	0.958
1:52881595:C:A	A625D	0.958
1:52860767:G:C	A349P	0.957
1:52866515:T:C	C447R	0.957
1:52857523:T:C	L261P	0.956
1:52864035:G:C	A402P	0.953
1:52877758:T:C	L540P	0.953
1:52857391:T:A	V217D	0.952
1:52885851:T:A	W655R	0.952
1:52885851:T:C	W655R	0.952
1:52866519:T:C	L448P	0.951

dbSNP variants (sampled 300 via entrez): RS1000031748 (1:52858422 C>T), RS1000050537 (1:52852268 CGAACTCCTGACCTCAT>C), RS1000067368 (1:52872209 C>G,T), RS1000118360 (1:52864793 C>T), RS1000212812 (1:52894258 T>C,G), RS1000222776 (1:52865295 A>G), RS1000243887 (1:52894072 A>G), RS1000277407 (1:52851790 C>T), RS1000325222 (1:52864214 T>A,C), RS1000335091 (1:52871878 C>T), RS1000429153 (1:52845805 G>T), RS1000445979 (1:52887411 C>G), RS1000504689 (1:52874556 A>C), RS1000528725 (1:52860443 G>A), RS1000691142 (1:52869172 A>C)

Disease associations

OMIM: gene MIM:618675 | 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
GCST004604_14	Hematocrit	1.000000e-09
GCST004625_4	Monocyte count	1.000000e-09
GCST010083_330	Hemoglobin levels	3.000000e-12
GCST90002383_325	Hematocrit	2.000000e-19
GCST90002384_542	Hemoglobin	2.000000e-14
GCST90002393_28	Monocyte count	3.000000e-17
GCST90002396_132	Mean reticulocyte volume	3.000000e-14
GCST90002403_6	Red blood cell count	3.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0005091	monocyte count
EFO:0004509	hemoglobin measurement
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
potassium chromate(VI)	increases 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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0ZW	MUSIi014-A	Induced pluripotent stem cell	Female
CVCL_A0ZX	MUSIi015-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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