ZNRD2

Summary

ZNRD2 (zinc ribbon domain containing 2, HGNC:11328) is a protein-coding gene on chromosome 11q13.1, encoding Protein ZNRD2 (O60232). Might play a role in mitosis.

This antigen is recognized by a subset of anti-centromere antibodies from patients with scleroderma and/or Sjogren’s syndrome. Subcellular localization has not yet been established.

Source: NCBI Gene 10534 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 22 total
• Druggable target: yes
• MANE Select transcript: NM_006396

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11328
Approved symbol	ZNRD2
Name	zinc ribbon domain containing 2
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	p27
Ensembl gene	ENSG00000173465
Ensembl biotype	protein_coding
OMIM	606044
Entrez	10534

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000309328, ENST00000526433, ENST00000526877, ENST00000527413, ENST00000527920, ENST00000531405, ENST00000533115, ENST00000913761, ENST00000913762, ENST00000913763

RefSeq mRNA: 2 — MANE Select: NM_006396 NM_001303024, NM_006396

CCDS: CCDS76434, CCDS8104

Canonical transcript exons

ENST00000309328 — 4 exons

Exon	Start	End
ENSE00001191899	65570604	65570755
ENSE00002161481	65571391	65571888
ENSE00002187462	65570477	65570510
ENSE00003634736	65570886	65570970

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 95.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.1407 / max 356.9203, expressed in 1824 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115172	62.1407	1824

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	95.43	gold quality
apex of heart	UBERON:0002098	95.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.11	gold quality
right coronary artery	UBERON:0001625	94.72	gold quality
gastrocnemius	UBERON:0001388	94.61	gold quality
popliteal artery	UBERON:0002250	94.53	gold quality
tibial artery	UBERON:0007610	94.52	gold quality
thoracic aorta	UBERON:0001515	94.36	gold quality
ascending aorta	UBERON:0001496	94.33	gold quality
aorta	UBERON:0000947	94.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.25	gold quality
lower esophagus	UBERON:0013473	94.24	gold quality
left coronary artery	UBERON:0001626	94.10	gold quality
right frontal lobe	UBERON:0002810	94.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.98	gold quality
muscle of leg	UBERON:0001383	93.96	gold quality
descending thoracic aorta	UBERON:0002345	93.90	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.76	gold quality
left uterine tube	UBERON:0001303	93.73	gold quality
cortical plate	UBERON:0005343	93.62	gold quality
ganglionic eminence	UBERON:0004023	93.48	gold quality
stromal cell of endometrium	CL:0002255	92.93	gold quality
prefrontal cortex	UBERON:0000451	92.89	gold quality
right atrium auricular region	UBERON:0006631	92.88	gold quality
body of uterus	UBERON:0009853	92.82	gold quality
body of stomach	UBERON:0001161	92.77	gold quality
granulocyte	CL:0000094	92.65	gold quality
right testis	UBERON:0004534	92.54	gold quality
endocervix	UBERON:0000458	92.52	gold quality
coronary artery	UBERON:0001621	92.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting ZNRD2, 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-520G-5P	99.99	66.76	658
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 2)

• The current results showed that p27 expression were associated with glioma grade. (PMID:19574837)
• Our method identified a strong relationship between p27 expression and prostate cancer recurrence. (PMID:21292307)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	znrd2	ENSDARG00000069109
mus_musculus	Znrd2	ENSMUSG00000079478
rattus_norvegicus	Znrd2	ENSRNOG00000012736
caenorhabditis_elegans		WBGENE00012643

Protein

Protein identifiers

Protein ZNRD2 — O60232 (reviewed: O60232)

Alternative names: Autoantigen p27, Protein zinc ribbon domain type 2, Sjoegren syndrome/scleroderma autoantigen 1, Zinc ribbon domain-containing protein 2

All UniProt accessions (6): O60232, E9PK41, E9PN57, G3V1B8, H0YEB6, H0YEK1

UniProt curated annotations — full annotation on UniProt →

Function. Might play a role in mitosis. Antigenic molecule. Could be a centromere-associated protein. May induce anti-centromere antibodies.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Cofactor. Binds 1 zinc ion per subunit.

RefSeq proteins (2): NP_001289953, NP_006387* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009563	ZNRD2_N	Domain
IPR051888	UPF0148_domain	Family

Pfam: PF06677

UniProt features (27 total): mutagenesis site 11, binding site 4, strand 2, turn 2, modified residue 2, initiator methionine 1, chain 1, sequence variant 1, region of interest 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6HCZ	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60232-F1	78.64	0.47

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 (4): 53; 56; 70; 73

Post-translational modifications (2): 2, 94

Mutagenesis-validated functional residues (11):

Position	Phenotype
2–148	cytoplasmic subcellular location.
2–84	cytoplasmic subcellular location.
85–199	ubiquitous intracellular location.
148–199	ubiquitous intracellular location.
173–199	ubiquitous intracellular location.
180	ubiquitous intracellular location; when associated with a-183; a-184; a-191; a-194 and a-197.
183	ubiquitous intracellular location; when associated with a-180; a-184; a-191; a-194 and a-197.
184	ubiquitous intracellular location; when associated with a-180; a-183; a-191; a-194 and a-197.
191	ubiquitous intracellular location; when associated with a-180; a-183; a-184; a-194 and a-197.
194	ubiquitous intracellular location; when associated with a-180; a-183; a-184; a-191 and a-197.
197	ubiquitous intracellular location; when associated with a-180; a-183; a-184; a-191 and a-194.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, chr11q13, WEI_MYCN_TARGETS_WITH_E_BOX, WTGAAAT_UNKNOWN, GOBP_MITOTIC_CELL_CYCLE, WINTER_HYPOXIA_METAGENE, SCHLOSSER_MYC_TARGETS_AND_SERUM_RESPONSE_UP, CUI_TCF21_TARGETS_2_UP, GOBP_CELL_DIVISION, JAIN_NFKB_SIGNALING, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, ENK_UV_RESPONSE_EPIDERMIS_UP, HUTTMANN_B_CLL_POOR_SURVIVAL_UP, LU_EZH2_TARGETS_UP, BRUINS_UVC_RESPONSE_EARLY_LATE

GO Biological Process (2): mitotic cell cycle (GO:0000278), cell division (GO:0051301)

GO Molecular Function (3): identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle	1
mitotic nuclear division	1
cellular process	1
protein binding	1
cation binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNRD2	FAM89B	Q8N5H3	591
ZNRD2	RAPGEF2	Q9Y4G8	590
ZNRD2	FRMD8	Q9BZ67	549
ZNRD2	RNF166	Q96A37	543
ZNRD2	DPF2	Q92785	502
ZNRD2	SLC25A45	Q8N413	497
ZNRD2	ASB7	Q9H672	453
ZNRD2	CDC42EP2	O14613	437
ZNRD2	PBLD	P30039	436
ZNRD2	RFLNA	Q6ZTI6	432
ZNRD2	TMTC2	Q8N394	429
ZNRD2	CRISPLD1	Q9H336	414
ZNRD2	FAM169BP	Q8N8A8	404
ZNRD2	RPAP3	Q9H6T3	403
ZNRD2	TIGD3	Q6B0B8	399

IntAct

134 interactions, top by confidence:

A	B	Type	Score
CCT7	ZNRD2	psi-mi:“MI:0915”(physical association)	0.830
ZNRD2	CCT7	psi-mi:“MI:0915”(physical association)	0.830
ZNRD2	CCT5	psi-mi:“MI:0915”(physical association)	0.740
CCT2	ZNRD2	psi-mi:“MI:0915”(physical association)	0.720
ZNRD2	CCT2	psi-mi:“MI:0915”(physical association)	0.720
CCNH	ZNRD2	psi-mi:“MI:0915”(physical association)	0.670
ZNRD2	CCNH	psi-mi:“MI:0915”(physical association)	0.670
ZNRD2	CCT3	psi-mi:“MI:0915”(physical association)	0.670
CCT3	ZNRD2	psi-mi:“MI:0915”(physical association)	0.670
ZNRD2	SUMO1P1	psi-mi:“MI:0915”(physical association)	0.560
ZNRD2	HEL-S-69	psi-mi:“MI:0915”(physical association)	0.560
ZNRD2	SNAPC5	psi-mi:“MI:0915”(physical association)	0.560
TRAF3IP3	ZNRD2	psi-mi:“MI:0915”(physical association)	0.560
HEL-S-100n	ZNRD2	psi-mi:“MI:0915”(physical association)	0.560
HEL-S-69	ZNRD2	psi-mi:“MI:0915”(physical association)	0.560
SNAPC5	ZNRD2	psi-mi:“MI:0915”(physical association)	0.560
SUMO1P1	ZNRD2	psi-mi:“MI:0915”(physical association)	0.560
ZNRD2	TRAF3IP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (390): SSSCA1 (Affinity Capture-MS), SSSCA1 (Two-hybrid), SSSCA1 (Two-hybrid), SSSCA1 (Two-hybrid), CCT7 (Two-hybrid), CCT2 (Two-hybrid), CCT5 (Two-hybrid), TRAF3IP3 (Two-hybrid), SUMO1P1 (Two-hybrid), SSSCA1 (Affinity Capture-MS), SSSCA1 (Two-hybrid), SSSCA1 (Affinity Capture-MS), ALS2CR11 (Two-hybrid), MYO15B (Two-hybrid), C20orf195 (Two-hybrid)

ESM2 similar proteins: A1L131, A4IFK7, C5IJB0, D3ZND0, F1MX48, O60232, O95400, P35689, Q0VCT3, Q17QX2, Q2KIJ6, Q2YD98, Q3ZBK7, Q3ZBN4, Q4R4I0, Q53GS7, Q5EAN7, Q5FVK6, Q5PPF5, Q5RAS2, Q5T0F9, Q68F60, Q69ZT1, Q6AYI4, Q6NU18, Q6TLH3, Q7L4P6, Q7TMX5, Q8BL74, Q8BRN9, Q8BSI6, Q8C0R7, Q8C6D4, Q8N5A5, Q8R322, Q8VDM1, Q91VL8, Q91WA6, Q91WR3, Q969X0

Diamond homologs: O60232, P56873

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of tubulin folding intermediates by CCT/TriC	7	58.0×	2e-09
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	7	56.0×	2e-09
Prefoldin mediated transfer of substrate to CCT/TriC	7	54.0×	2e-09
BBSome-mediated cargo-targeting to cilium	5	48.7×	2e-06
Chaperonin-mediated protein folding	8	47.1×	7e-10
Association of TriC/CCT with target proteins during biosynthesis	8	45.9×	7e-10
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	7	41.2×	1e-08
Protein folding	8	40.7×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	7	75.4×	5e-10
binding of sperm to zona pellucida	6	37.2×	1e-06
protein folding	8	12.2×	2e-05
protein stabilization	12	11.8×	4e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

514 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65570507:GCTG:G	donor_gain	1.0000
11:65570510:GGTGA:G	donor_loss	1.0000
11:65570511:GTGA:G	donor_loss	1.0000
11:65570603:GAA:G	acceptor_gain	1.0000
11:65570751:GCGGG:G	donor_gain	1.0000
11:65570753:GGG:G	donor_gain	1.0000
11:65570754:GG:G	donor_gain	1.0000
11:65570754:GGG:G	donor_gain	1.0000
11:65570755:GG:G	donor_gain	1.0000
11:65570756:G:GG	donor_gain	1.0000
11:65570876:T:A	acceptor_gain	1.0000
11:65570877:G:A	acceptor_gain	1.0000
11:65570881:CGTA:C	acceptor_loss	1.0000
11:65570882:GTAG:G	acceptor_loss	1.0000
11:65570883:TA:T	acceptor_loss	1.0000
11:65570884:A:AG	acceptor_gain	1.0000
11:65570884:AGAC:A	acceptor_gain	1.0000
11:65570885:G:GC	acceptor_gain	1.0000
11:65570885:GA:G	acceptor_gain	1.0000
11:65570885:GAC:G	acceptor_gain	1.0000
11:65570885:GACG:G	acceptor_gain	1.0000
11:65570885:GACGA:G	acceptor_gain	1.0000
11:65570966:TCCCG:T	donor_gain	1.0000
11:65570967:CCCG:C	donor_gain	1.0000
11:65570969:CG:C	donor_gain	1.0000
11:65570970:GG:G	donor_gain	1.0000
11:65570971:G:GG	donor_gain	1.0000
11:65572957:GATG:G	donor_gain	1.0000
11:65572961:G:GG	donor_gain	1.0000
11:65572961:GTGA:G	donor_loss	1.0000

AlphaMissense

1259 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65570727:T:C	M48T	1.000
11:65570922:T:C	C70R	1.000
11:65570709:T:C	L42P	0.999
11:65570712:T:C	L43P	0.999
11:65570896:T:C	L61P	0.999
11:65570923:G:A	C70Y	0.999
11:65570924:C:G	C70W	0.999
11:65570959:A:T	K82I	0.999
11:65570960:A:C	K82N	0.999
11:65570960:A:T	K82N	0.999
11:65570699:G:C	G39R	0.998
11:65570727:T:A	M48K	0.998
11:65570727:T:G	M48R	0.998
11:65570741:T:C	C53R	0.998
11:65570750:T:C	C56R	0.998
11:65570751:G:A	C56Y	0.998
11:65570896:T:A	L61H	0.998
11:65570926:T:A	V71E	0.998
11:65570931:T:C	C73R	0.998
11:65570961:G:C	D83H	0.998
11:65570962:A:C	D83A	0.998
11:65570962:A:T	D83V	0.998
11:65571409:C:A	A92D	0.998
11:65570667:G:C	R28P	0.997
11:65570700:G:A	G39D	0.997
11:65570717:G:C	G45R	0.997
11:65570718:G:A	G45D	0.997
11:65570718:G:T	G45V	0.997
11:65570728:G:A	M48I	0.997
11:65570728:G:C	M48I	0.997

dbSNP variants (sampled 300 via entrez): RS1000078512 (11:65569791 G>C), RS1001342869 (11:65570438 A>C), RS1001625621 (11:65570229 G>A,T), RS1003090160 (11:65569657 A>C), RS1003738204 (11:65572311 G>C), RS1003956448 (11:65569178 G>A), RS1004176215 (11:65569749 G>A), RS1004294086 (11:65570008 G>A,C), RS1005296280 (11:65571205 C>T), RS1007775895 (11:65571372 C>T), RS1008563064 (11:65568873 G>C), RS1009891935 (11:65569340 G>A), RS1010096727 (11:65569857 G>A,C), RS1011533275 (11:65570371 G>A,C), RS1014119631 (11:65572196 G>A,T)

Disease associations

OMIM: gene MIM:606044 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000817_71	Height	4.000000e-13
GCST002481_8	Acne (severe)	3.000000e-11
GCST002626_8	Vertical cup-disc ratio	5.000000e-13
GCST002762_13	Optic cup area	2.000000e-09
GCST002762_28	Optic cup area	7.000000e-11
GCST004075_5	Vertical cup-disc ratio	3.000000e-17
GCST004075_6	Vertical cup-disc ratio	8.000000e-18
GCST004137_20	Optic cup area	2.000000e-12
GCST004137_36	Optic cup area	9.000000e-11
GCST005194_195	Coronary artery disease	3.000000e-10
GCST007015_4	Lumbar spine bone mineral density (integral)	2.000000e-06
GCST009404_22	Optic cup area	1.000000e-10
GCST009412_9	Vertical cup-disc ratio	5.000000e-14
GCST010002_240	Refractive error	3.000000e-11
GCST90011770_56	Glaucoma (primary open-angle)	4.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0007620	volumetric bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105996 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Cyclosporine	increases expression	3
butyraldehyde	increases expression	1
cupric chloride	increases expression	1
cylindrospermopsin	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Atrazine	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Vitamin K 3	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012909	Binding	Binding affinity to SSSCA1 in human Jurkat cell extract up to 5 uM after 1 hr using NHS-activated sepharose coupled Piperazin-1-yl(4-(tetrazolo[1,5-a]quinoxalin-4-ylamino)phenyl)-methanone by mass spectrometry based chemoproteomic assay	Discovery of a Highly Selective Tankyrase Inhibitor Displaying Growth Inhibition Effects against a Diverse Range of Tumor Derived Cell Lines. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LP	Abcam HEK293T ZNRD2 KO	Transformed cell line	Female
CVCL_D9W3	Ubigene HEK293 ZNRD2 KO	Transformed cell line	Female
CVCL_E0TD	Ubigene HeLa ZNRD2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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